MLリソース：Androgen/男性ホルモン
ｈｙｐｏｇｏｎａｄｉｓｍ（ｈｉ′ｐｏ‐ｇｏ′ｎａｄ‐ｉｚｍ）．性機能低下（不全）〔症〕，生殖機能不全（性腺の機能不全で，生殖発生および性腺ホルモン分泌の一方または双方の欠損によって発現するものなどがある．萎縮あるいは二次的性徴の発現欠如という結果となり，思春期男子に起こったときは，体幹が短く肢体が長いという，特徴ある体型に変わる）
●個別収録製品 [1164]testosterone buccal system (Striant [Columbia Labs.,Inc.]) [1164]testosterone gel(Testim [Auxilium Pharma]) [1080]testosterone gel (Androgel [Unimed]) ●追加情報★IMS Health Analyzes Testosterone Use in the U.S.In the IMS report, “The Extent and Nature of Testosterone Use,” it is estimated that 819,000 male patients were treated with testosterone last year, representing the 29% increase.
According to the Food and Drug Administration, between four and five million American men may have low testosterone, a condition also known as hypogonadism*.
The report also analyzed last year’s patient use by delivery method and noted trends. Data suggests gels and injections show similar distributions, followed by patches and oral tablets. In the retail setting, data indicate approximately 42 percent of all TRT patients use gels; 32 percent use injections; 20 percent use patches and 6 percent use oral tablets.
Additionally, an age breakdown revealed that most TRT patients (approximately 86 percent) in 2002 were under the age of 65. Fifty-seven percent of patients were between the ages of 46-65 years; 29 percent were between 18-45 years; and one percent was below the age of 18. Only 13 percent of the patients were over age 65.
[1368]●testosterone (Axiron Topical solution [Eli Lilly])日本語版註）testosterone (Axiron Topical solution [Eli Lilly])
【別名】 【開発元】創製豪Acrux Ltd [DBR_ID]46073-246
【化学名】17-beta hydroxyandrost-4-en-3-one
【承認】FDA申請=3-Sep-2009 - 27-Jan-2010[Acrux Ltd]、FDA承認=23-Nov-2010、米国発売31-Mar-2011[Lilly] ; 【製剤】AXIRON (testosterone) topical solution is available as a metered-dose pump. One pump actuation(1.5mL) delivers 30 mg of testosterone. Each metered-dose pump is supplied with an applicator. 【適応】indicated for replacement therapy in males for conditions associated with a deficiency or absence of endogenous testosterone: (1)Primary hypogonadism (congenital or acquired) (2)Hypogonadotropic hypogonadism (congenital or acquired) 【用法用量】１日１回朝60mg(ポンプ１回30mg定量x2回噴霧)
【作用】Endogenous androgens, including testosterone and dihydrotestosterone (DHT), are responsible for the normal growth and development of the male sex organs and for maintenance of secondary sex characteristics. These effects include the growth and maturation of prostate, seminal vesicles, penis and scrotum; the development of male hair distribution, such as facial, pubic, chest and axillary hair; laryngeal enlargement, vocal cord thickening, alterations in body musculature and fat distribution. Testosterone and DHT are necessary for the normal development of secondary sex characteristics. Male hypogonadism results from insufficient secretion of testosterone and is characterized by low serum testosterone concentrations. Signs/symptoms associated with male hypogonadism include erectile dysfunction and decreased sexual desire, fatigue and loss of energy, mood depression, regression of secondary sexual characteristics and osteoporosis.Male hypogonadism has two main etiologies. Primary hypogonadism is caused by defects of the gonads, such as Klinefelter’s Syndrome or Leydig cell aplasia, whereas secondary hypogonadism is the failure of the hypothalamus (or pituitary) to produce sufficient gonadotropins (FSH, LH). 【特徴】新剤型
【製品情報】www.axiron.com 【添付文書】Axiron -PI
【提携】[16-Mar-2010] Eli LillyはAcruxからAXIRONの全世界独占販売権を獲得。 【EU】
【日本】未開発 【その他】
[1362]●テストステロンゲルtestosterone Gel(Fortesta - Endo)日本語版註）テストステロンゲルtestosterone Gel(Fortesta - Endo)
【別名】 【開発元】Endo Pharmaceuticals [DBR_ID]
【化学名】17-beta hydroxyandrost-4-en-3-one
【承認】FDA申請=31-May-2002、FDA承認=29-Dec-2010、米国発売3-Mar-2011 ; 【製剤】FORTESTA (testosterone) Gel is supplied as a metered-dose pump. One pump actuation delivers 10 mg of testosterone. each container is capable of dispensing 120 pump actuations. One pump actuation dispenses 0.5 g of gel. 【適応】indicated for replacement therapy in males for conditions associated with a deficiency or absence of endogenous testosterone: 1)(原発性性腺機能低下症) Primary hypogonadism (congenital or acquired) 2)(低ゴナドトロピン性性機能不全) Hypogonadotrophic hypogonadism (congenital or acquired) 【用法用量】初回１日１回朝 testosterone 40mg(4 pump actuations)を塗布。 70mg迄増量可。
【作用】Endogenous androgens, including testosterone and dihydrotestosterone (DHT), are responsible for the normal growth and development of the male sex organs and for the maintenance of secondary sex characteristics. These effects include the growth and maturation of the prostate, seminal vesicles, penis and scrotum; the development of male hair distribution, such as facial, pubic, chest and axillary hair; laryngeal enlargement, vocal cord thickening, alterations in body musculature and fat distribution. Testosterone and DHT are necessary for the normal development of secondary sex characteristics. Male hypogonadism results from insufficient production of testosterone and is characterized by low serum testosterone concentrations. Symptoms associated with male hypogonadism include erectile dysfunction and decreased sexual desire, fatigue and loss of energy, mood depression, regression of secondary sexual characteristics, and osteoporosis.Male hypogonadism can present as primary hypogonadism caused by defects of the gonads, such as Klinefelter’s Syndrome or Leydig cell aplasia while secondary hypogonadism is the failure of the hypothalamus or pituitary to produce sufficient gonadotropins (FSH, LH). 【特徴】
【製品情報】www.fortestagel.com 【添付文書】FORTESTA-PI
【提携】 【EU】
【日本】未開発 【その他】
【日本語版コメント1368〜性腺機能低下治療薬テストステロン局所用液(Axiron - Lilly)】
日本のテストステロン製剤は、錠剤と注射剤のみで、経皮製剤は販売されていない(OTCでは軟膏剤あり)。 例えばエナルモン錠25mg(あすか製薬；メチルテストステロン)の適応は「男子性腺機能不全(類宦官症) 、造精機能障害による男子不妊症 、末期女性性器癌の疼痛緩和，手術不能の乳癌」。
【日本語版コメント1362〜性腺機能低下に対する新規テストステロンゲル(Fortesta - Endo)】
日本では性腺機能低下症は、極めて稀な疾患で薬剤需要が少ないため、外用テストステロン製剤は一般用のグローミン軟膏[大東製薬工業]のみ。 米国では医療用としてテストステロン埋め込みペレットTESTOPEL[SLATE PHARMS]、持続性バッカル製剤STRIANT[ACTIENT PHARMS]、外用液AXIRON[ELI LILLY]、経皮フイルムANDRODERM[WATSON]、経皮ゲルANDROGEL[ABBOTT]およびTESTIM[AUXILIUM PHARMS]と実に多彩だ。
【市場】
IMS HealthによるとTestosteron市場規模は、$49 million(1997)から$216 million(2002)と大きく増加 (CBS News | Testosterone In A Tube | May 20, 2003)。といっても規模はまだ小さく、Androgel[Solvay] $196 million(+51;2002年)と大半を占める。 しかし新規参入のAuxilium社は2008年に20億ドルを見込む。 因みに米国以外は市場と言えるものはない。
【解説資料】 アナボリックステロイド百科事典: Testosterone テストステロン メルクマニュアル第17節 泌尿生殖器疾患 勃起機能不全 HRT Online: Testosterone 【疫学資料】 Auxilium社によると米国でhypogonadism男性は推定4-500万人。うちtestosterone療法を受けているのは20%。 【臨床ガイドライン】 AACE Hypogonadism Guidelenes 2002[pdf,18p] -Hypogonadismに関して最も信頼性が高く解説書としても優れる AACE Male Sexual Dysfunction Guidelenes 2003[pdf] 【リソース】 MEDLINEplus: Impotence 【主要サイト】 AACE.COM: The Official Web Site of The American Association of Clinical Endocrinologists[このサイトの特徴は内分泌関連臨床ガイドラインが充実] ●American Society of Andrology[ASA] - 機関誌Journal of Andrology ■男性更年期障害 Male HRT/Andropause ●www.andropause.com by Organon ●GET BACK ON TRACK - testosterone deficiency and treatment supported by [Bayer Schering Pharma]Deficiency Testosterone
●解説
●アナボリックステロイド百科事典: Testosterone テストステロン 筋量、筋力アップに適しているステロイドといえば、アナドロール、ダイアナボール、パラボラン、その他を思い浮かべるであろう。しかしもっとも早く筋量、筋力を増大させるのはテストステロンである。アンドロゲニック作用も強いが、アナボリック作用も見逃すことが出来ない。
テストステロンは経口摂取は出来ないため、注射剤にて摂取する。（例外もある。）バリエーションは多く、Testosterone/Enanthate,Cypionate,Propionate等があり主な違いは体内の滞留期間である。滞留期間ではPropionate(3日間）＜Cypionate(１−２週間）＜ Enanthate(２−４週間）となる。
ちなみに一番滞留期間が長いテストステロンエステルは Testosterone-tras-4-n-butylcyclohexyl-carboxylateであり動物実験においては去勢した猿に40mg注射したところ、１６週間テストステロンレベルを正常値にキープしたと報告されている。また数種類のテストステロンをブレンドされたものもありSutanon,Sten,Omnadrenがある。とりわけSustanonはビルダーの中では人気がある。テストステロンを摂取するとエネルギーの向上を感じ、トレーニング後の回復のスピードアップを体感できる。もちろんパワー筋量の増加のスピードも驚異的である。しかしこれは副作用の体内の水分保留により、体重が増加して使用重量がアップしたにすぎず、実際の筋量アップは使用をやめて水がぬけた後の増加分である。とはいえ６−８週間で１０kgの増加は珍しくはない。副作用もひどく、使用にさいしては十分注意しなければならない。
わたしが体験した副作用としては通勤中に電車に飛び乗るとき１０−２０Mダッシュしただけで脛、ふくらはぎ、大腿筋に強烈なパンプをおこし動けなくなり何回か乗り遅れたことがある。特に脛の焼けるようなパンプはすさまじく一歩も動けなくなるのは狂言ではない。おかげでナチュナルではびくともしなかったカーフが気がついたら３−４cmサイズアップしてしまった。（普段のトレーニングにカーフのトレーニングは諦めもあり現在でもルーチンにはない。）ワールドアナボリックレヴィウーによればテストステロンはミスターオリンピアでも効くほど強力でありステロイド初心者は手を出さないほうが無難と明記してある。それでも使用したいならば量を加減して使うべきである。いきなり500mg-1000mg使用して睾丸の機能不全になっても責任はとりません。
average dosage 250mg-1000mg/week high dosage 1000mg-3000mg/week mega dosage 500mg-2000mg/day Links to other sites on the Web 英語ステロイド販売 英語ステロイド販売 日本語成長ホルモン激安 日本語ステロイド販売 英語ステロイド販売 メキシコの薬局 スペイン語 ステロイド情報をお寄せ下さい。 c 1997 musclek@gold.ocn.ne.jp
●SRL Handbook: テストステロン /TS : testosterone ★臨床的意義
男性の睾丸から分泌される主要なアンドロゲン（C19ステロイド）で，下垂体前葉から分泌されるLHおよび，視床下部から放出されるLH-RHを介する。テストステロン，フリーテストステロンと共に性腺機能の判定及び男性化の病態解明に重要な意味をもつ。なお，女性では副腎系の機能検査としても重要な意義を持つ。更にフリーテストステロンは直接生物活性を示すため肝疾患，甲状腺機能亢進症，妊娠などで特異結合蛋白（SHBG）に変動がみられる場合に，テストステロンよりもこれらの影響を受けずに性腺機能を反映する。
★異常値を示す疾患 高値疾患 男性；・男性ホルモン産生腫瘍 ・先天性副腎過形成 女性；・男性化副腎腫瘍 ・先天性副腎過形成 ・男性化卵巣腫瘍 低値疾患 男性；・無精巣症 ・思春期前去勢 ・ゴナドトロピン単独障害 ★検査法・基準値 検査方法 検査材料 基準値 --------------------------------------------------------------- RIA固相法テストステロン 血漿・血清 M 250〜1100 ng/dl F 10〜60 ng/dl 蓄尿 M 10〜120 μg/day F 5〜36 μg/day RIA固相法フリーテストステロン 血清 M 14〜40 pg/ml F 3 pg/ml以下 --------------------------------------------------------------- ★検体採取・測定条件 TSは血清または専用容器EDTA-2Na血漿，および蓄尿。フリーテストステロンは，血清分離後の室温保存で低下傾向を示すため，必ず凍結保存をする。 ★生理的変動 男性では日内変動（朝高く，夕方低下）が見られるが女性では見られない。 血中の98％は蛋白と結合し遊離型は２％にすぎない。睡眠中のTSが遊離型を反映するといわれている。 ★関連項目 LH FSH 17-KS E2 プロゲステロン アンドロステンジオン
●[2000年1月13日 (VOL.33 NO.2) p.19]運動選手と筋肉増強薬 薬剤に頼るよりトレーニングプログラムの採用を
〔ニューヨーク〕 錠剤の服用で筋肉を増強することが可能か，またそうしてもよいかについて，南カリフォルニア大学（ロサンゼルス）整形外科のClarence L. Shields, Jr.臨床准教授は「運動能力や外見を改善するために補充薬，特に蛋白同化ステロイドを使おうと思っている選手がいたなら，考え直すようにアドバイスするほうがよい」と当地で開催された米国整形外科学会（AAOS）の「最新の整形外科」講演で述べた。
同准教授は，若手の運動選手に対して「ロッカールーム，ジム，競技大会などで見たことやうわさに基づいて決心するのではなく，その大部分が遺伝的に既定されている筋肉量を増加させる優れたトレーニングプログラムがあることを理解する」よう警告した。さらに，自己投与されるいくつかの補充薬の長期的影響は不明である，とも述べた。
★クレアチンにもリスク
Shields准教授は「エネルギー放出補充薬であるクレアチンは，野球，短距離走など，瞬発力を必要とする運動での成果を改善するだろう。しかし，長距離走，水泳，自転車競技などの持久運動には効果がない。クレアチンの使用によって筋肉線維は太くなり，身体はより高い抵抗トレーニング負荷に適応するが，クレアチンの副作用を見過ごしてはいけない。クレアチンはステロイドより安全であるが，リスクがないわけではない。クレアチンによって重度の消化管症状，ハムストリング筋の断裂，重度の腎障害が発生する可能性がある。さらに，不幸なことにクレアチンを服用している人の大部分では，服用前に腎機能検査を受けていないため，腎機能がボーダーラインにある人がクレアチンを服用すると重大な腎障害が発生する可能性がある」と述べた。
クレアチンはおもに身体の骨格筋中に認められる。クレアチンは栄養補充薬で，処方薬ではないため一般用医薬品として購入でき，その品質はメーカーによってさまざまである。肝臓は，身体が毎日必要とする 2 gのクレアチンのうち 1 gを産生する。赤肉が残りの 1 gを供給するので，菜食主義者の運動選手にとって問題となっている。
Shields准教授は「通常，運動選手は 5 gのクレアチンを 1 日 4 〜 5 回摂取することで，1 週間安全にクレアチンを“短期摂取”することができる。これによって，筋肉に取り込まれるクレアチン量が35％増加する。健康な男性では，クレアチンを 5 〜 7 日間服用しても腎臓に変化は見られない。しかし，1 週間以上の服用あるいは 1 日20〜25g以上の服用によって発生する変化については不明である。筋肉生検から，このプロトコルによって筋肉のクレアチン含量は30％増加することが示されている。炭水化物の摂取によってクレアチンの吸収を増加させることができるが，その吸収率は遺伝的影響もある。クレアチンの血中濃度が低い運動選手は，高いクレアチン吸収率を示す。身体中のクレアチンリン酸の消耗は疲労と関連する」と説明した。
★ASなどは使用しない
体力運動（フットボールやレスリングなど）のための筋力および筋肉量の増加，エネルギー，性的刺激，満足感などの増加を目的として，多くの運動選手は副腎アンドロゲン（ASとして知られているアンドロステンジオン）を服用している。これは赤肉や植物中に含まれる天然ステロイドで，肝臓でテストステロンに変換される。米国ナショナルフットボールリーグ（NFL），全米大学競技協会（NCAA），国際オリンピック委員会（IOC）の禁止にもかかわらず，ASは一般用医薬品として入手可能である。
長期的影響は不明であるが，にきび，前立腺肥大，高比重リポ蛋白（HDL）の低下，精巣の萎縮などが報告されている。女性では，顔面の発毛，声の変化，月経不順が認められる。幸い，これらの影響のいくつかは可逆的である。
DHEAとして知られるデヒドロエピアンドロステロンは，別種のテストステロン前駆物質である。この補充薬は体力，エネルギー，筋肉量を増加させ，満足感をもたらする。グループ競技などでより強い体力を必要とする選手が使用し，一般用医薬品として入手可能であり，副作用はASと同様である。妊娠中，授乳中の母親には禁忌である。
Shields准教授は「運動選手が筋肉増強薬，特に蛋白同化ステロイドを服用していないかどうかを，確認すべきである。増強薬は筋肉のサイズを増加させるが，骨の成長を妨げ，腱を弱め，性格を攻撃的・闘争的にし，抑うつの原因となる可能性がある」と述べた。
■MEDLINEplus: Androgens (Systemic)
Contents of this page: Brand Names Category Description Before Using This Medicine Proper Use of This Medicine Precautions While Using This Medicine Side Effects of This Medicine Additional Information from Micromedex, Inc. and USP DI Last updated: 03 May 2000
●データ
●臨床ガイドラインなど
●National Guideline Clearinghouse ●AACE medical guidelines for clinical practice for the diagnosis and treatment of hyperandrogenic disorders. American Association of Clinical Endocrinologists - Medical Specialty Society. 2001 Mar-Apr. 15 pages. NGC:002073
●American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. American Association of Clinical Endocrinologists - Medical Specialty Society; American College of Endocrinology - Medical Specialty Society. 1996 (revised 2002). 13 pages. NGC:002751
●American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of male sexual dysfunction: a couple's problem--2003 update. American Association of Clinical Endocrinologists - Medical Specialty Society; American College of Endocrinology - Medical Specialty Society. 1998 (revised 2003). 19 pages. NGC:002951
●The primary care management of erectile dysfunction. Department of Veterans Affairs - Federal Government Agency [U.S.]; Veterans Health Administration - Federal Government Agency [U.S.]. 1999 Jun. 67 pages. NGC:001803
■AACE On-Line: Hypogonadism |pdf●性機能障害（testosterone/gnrh）[1998]
-AACE Clinical Practice Guidelines for the Evaluation and Treatment of Hypogonadism in Adult Male Patients Developed by The American Association of Clinical Endocrinologists and The American College of Endocrinology , AACE Hypogonadism Task Force Steven Michael Petak, M.D.,JD, F.A.C.E., Chair H. Jack Baskin, M.D., F.A.C.E. Donald A. Bergman, M.D., F.A.C.E. Richard A. Dickey, M.D., F.A.C.E. Howard A. Nankin, M.D., F.A.C.E. ABSTRACTIn these clinical practice guidelines, specific recommendations are made for determining the most effective methods of diagnosing and treating hypogonadism in adult male patients. The target populations for these guidelines include the following: (1) males with primary testicular failure requiring testosterone replacement (hypergonadotropic hypogonadism); (2) males with gonadotropin deficiency or dysfunction who may have received testosterone replacement therapy or treatment for infertility (hypogonadotropic hypogonadism); and (3) aging men with symptoms relating to testosterone deficiency who could benefit from replacement therapy. Initial hormonal evaluation generally consists of a testosterone determination, in conjunction with a free testosterone or sex hormone-binding globulin level, in patients with clear symptoms and signs but normal-range total testosterone, follicle-stimulating hormone, luteinizing hormone, and prolactin levels. Other possible tests include semen analysis, pituitary imaging studies, genetic studies, bone densitometry, testicular biopsy, and specialized hormonal dynamic testing. Therapeutic options generally consist of testosterone replacement by injections or patches in hypergonadotropic patients and in hypogonadotropic patients not interested in fertility. In hypogonadotropic patients interested in fertility, gonadal stimulation options can be considered, including human chorionic gonadotropin stimulation therapy with or without human menopausal gonadotropin (or follicle-stimulating hormone) or gonadotropin-releasing hormone pump therapy. These therapies may be combined with assisted reproductive technologies such as in vitro fertilization with intracytoplasmic sperm injection, which may allow pregnancy to occur with very low numbers of sperm. (Endocr Pract. 1996; 2:440-453)
FOREWORD
Guidelines are systematically developed statements to assist health-care professionals in medical decision making for specific clinical conditions. Most of the content herein is based on literature reviews. In areas of uncertainty, professional judgment was applied.
These guidelines are a working document that reflects the state of the field at the time of publication. Because rapid changes in this area are expected, periodic revisions are inevitable. We encourage medical professionals to use this information in conjunction with their best clinical judgment. The presented recommendations may not be appropriate in all situations. Any decision by practitioners to apply these guidelines must be made in light of local resources and individual patient circumstances.
★MISSION STATEMENT
Hypogonadism is defined as "inadequate gonadal function, as manifested by deficiencies in gametogenesis and/or the secretion of gonadal hormones" (1). In addressing the issues related to hypogonadism in adult male patients, comparisons will inevitably be made with hypogonadal disorders of women. Clearly, hormone replacement in estrogen-deficient women is associated with dramatic decreases in cardiovascular risk and osteoporosis-related fracture risk and with enhanced emotional as well as physical well-being. These benefits are being judged against the possibly increased risk of breast cancer. Physicians and female patients are becoming well-informed advocates of hormone replacement choices, and active research is being conducted to address the remaining concerns.
In contrast, men with hypogonadal disorders have symptoms that are often denied by the patient and ignored by the physician. In addition, diagnostic evaluation and therapeutic options are poorly understood. With a longer life span and with advances in the treatment of cardiovascular disease, some aging men suffer from associated decreases in testosterone levels that may increase the risk of osteoporosis, sexual dysfunction, fatigue, and mood disturbances in a fashion similar to that in their female counterparts. Just as breast cancer has been a concern in women, prostate cancer in men remains a common problem that demands further research efforts and also is an issue in the consideration of testosterone replacement therapy.
Of prime consideration is the paucity of long-term research studies of the identification of men at risk for complications related to a decreased testosterone level, optimal assessment of such patients, optimal treatment, and potential complications relating to long-term therapy.
These guidelines on the evaluation and treatment of hypogonadism in adult male patients represent not only a source of guidance for health-care professionals but also an appeal to clinicians to increase their awareness of the problem and to discuss these issues with their at-risk patients. With growing awareness and increased research efforts, both the duration and the quality of life for aging men will improve.
★GENERAL MANIFESTATIONS
Hypogonadism may manifest with testosterone deficiency, infertility, or both conditions. Symptoms of hypogonadism depend primarily on the age of the male patient at the time of development of the condition. Hypogonadism is seldom recognized before the age of puberty unless it is associated with growth retardation or other anatomic or endocrine abnormalities.
When hypogonadism develops before the age of puberty, the manifestations are those of impaired puberty:
Small testes, phallus, and prostate
Scant pubic and axillary hair
Disproportionately long arms and legs (from delayed epiphyseal closure)
Reduced male musculature
Gynecomastia
Persistently high-pitched voice
Postpubertal loss of testicular function results in slowly evolving subtle clinical symptoms and signs. In aging men, these symptoms and signs may be difficult to appreciate because they are often attributed to "getting older." The growth of body hair usually slows, but the voice and the size of the phallus and prostate remain unchanged. Temporal hair recession and balding usually do not occur and would not be expected to prompt a patient to seek medical attention. Patients with hypogonadism may have the following findings:
Progressive decrease in muscle mass
Loss of libido
Impotence
Oligospermia or azoospermia
Occasionally, menopausal-type hot flashes (with acute onset of hypogonadism)
The risk of osteoporosis and attendant fractures is increased. Many cases of hypogonadism are disclosed during the course of infertility evaluations.
★EVALUATION[略]
Gonadotropins[略]
Dynamic Tests
★DIFFERENTIAL DIAGNOSIS AND SPECIAL CONSIDERATIONS
The differential diagnosis of hypogonadism includes a large and diverse group of disorders affecting the testicles directly or affecting hypothalamic-pituitary regulation of the testes. The clinical setting, history, physical examination, and clinical judgment will, to a large degree, determine which possible etiologic factors are present. These guidelines summarize the various disorders but are not intended to be comprehensive (16).
Hypergonadotropic Hypogonadism
Patients with hypergonadotropic hypogonadism may have some or all of the following characteristic findings:
Hypogonadism
Increased FSH level
Increased LH level
Low testosterone level
Impaired production of sperm
Klinefelter's Syndrome
Klinefelter's syndrome is caused by extra X chromosomes present in the male karyotype and occurs in about 1 in every 400 men (5). The most common karyotype is 47,XXY; mosaicism is sometimes present (in about 1 in every 400 men) (17). Men with Klinefelter's syndrome classically have small, firm testes (generally less than 2 mL), gynecomastia, eunuchoid habitus, and increased gonadotropin levels. Although production of testosterone is low, high levels of SHBG may result in normal-range testosterone levels in about 40% of patients with Klinefelter's syndrome. These patients have azoospermia, but those with mosaicism may have some spermatogenesis and may produce some pregnancies early in their reproductive lives. Virilization may begin with puberty but frequently fails to progress. Gynecomastia is often present and frequently necessitates surgical therapy. Bone density is significantly lower than for age-matched male control subjects. Autoimmune disorders are present with increased frequency in patients with Klinefelter's syndrome and may respond favorably to testosterone therapy (18).
Other Genetic Syndromes
47,XYY Syndrome. - The 47,XYY karyotype, which occurs in about 0.1% of males, has been thought to be associated with aggressive behavior in some men with the disorder. Affected patients may have azoospermia in association with maturation arrest of the germinal epithelium. Usually, serum FSH levels are increased, but Leydig cell function is normal, as are testosterone and LH levels.
Dysgenetic Testes. - Dysgenetic testes may occur in conjunction with mosaicism; the patient may have an XO karyotype, a mixed XO/XY karyotype, or pure XY with streak gonads. Occurrence of pure gonadal dysgenesis in conjunction with an XY karyotype and streak gonads imposes an increased risk of malignant disease, which necessitates gonadectomy. Such patients generally have genital ambiguity.
Androgen Receptor Defects. - Patients with androgen receptor defects have an XY genotype and variable phenotype, depending on the degree of receptor defect. Such syndromes include testicular feminization, Reifenstein's syndrome, and other partial defects, as discussed in the following paragraphs.
Testicular Feminization. - Patients with testicular feminization have a female phenotype but a blind vaginal pouch. Testosterone receptor is nonfunctional or absent. Laboratory testing shows normal to high male range testosterone and increased gonadotropin levels. The testes should be removed after puberty because of an increased risk of a malignant lesion. Administration of testosterone yields no response.
Reifenstein's Syndrome. - In Reifenstein's syndrome, patients have a male phenotype with variable pseudohermaphroditism. A partial androgen receptor defect is present; testosterone and gonadotropin levels are increased. Abdominal testes should be removed because of the risk of a malignant lesion. If hypospadias is present, surgical correction of the genitalia may be needed. Any significant gynecomastia may also need surgical correction. Patients may respond to high doses of testosterone.
Other Syndromes. - Some male patients with gynecomastia or oligospermia may have partial androgen insensitivity in association with mild increases in testosterone and gonadotropin levels.
5a-Reductase Deficiency. - An autosomal recessive condition, 5a-reductase deficiency is associated with an XY genotype. The patients, however, have genital ambiguity until puberty, when increasingly male features develop. The diagnosis is based on clinical manifestations and an increased testosterone/dihydrotestosterone ratio both after puberty and in response to hCG before puberty. Sexual assignment is an issue, and patients may need corrective surgical procedures that necessitate specialty consultation.
Myotonic Dystrophy. - Myotonic dystrophy occurs only in male patients, by transmission from father to son. Because testicular failure usually occurs around age 40 years, patients often have children at risk for the disease.
Cryptorchidism
Unilateral or bilateral cryptorchidism can occur. The incidence of this condition is 3 to 4% at birth, but most testes ultimately descend. Thus, the 1-year incidence is about 0.8%. Because normal testicular descent requires normal pituitary function and dihydrotestosterone levels, the incidence of cryptorchidism is increased in patients with Kallmann's syndrome. Problems associated with the management of cryptorchidism include distinguishing between cryptorchidism and retractile testes and recommending medical treatment with hCG or surgical therapy in an infant (19). Generally, the objective is to bring the undescended testicle into the scrotum before 1 to 2 years of age - to decrease the risk of gonadal malignant lesions associated with abdominal testes and to improve fertility potential. In prepubertal boys, hCG treatment should generally be used initially for 4 weeks to determine whether descent occurs before operative intervention is considered. Discussion of these problems is beyond the scope of these guidelines; appropriate specialty consultation should be obtained.
Vanishing Testes Syndrome (Congenital Anorchism or Prepubertal Functional Castrate)
The initial manifestation of the vanishing testes syndrome is sexual immaturity in a male patient. The cause is unclear, but the syndrome may be due to testicular torsion during fetal life after sufficient testosterone exposure to produce masculinization of the reproductive tract. Impalpable testes suggest the possibility of cryptorchidism. FSH and LH levels are increased, and testosterone levels are low. If the LH levels are only minimally increased, hCG stimulation testing of the gonad should be done. With vanishing testes syndrome, no response would be demonstrated. A response to hCG stimulation would raise the possibility of intra-abdominal testes, which would necessitate further evaluation because of the possibility of malignant transformation. In this setting, an MRI is recommended to assess the possibility of a retained intra-abdominal dysgenetic gonad because this would be associated with an increased risk of a malignant lesion and would necessitate removal.
Hemochromatosis
Iron overload may lead to primary gonadal failure or sometimes hypothalamic-pituitary dysfunction that results in secondary gonadal failure (20). The diagnosis is made in the setting of associated findings of hemochromatosis in conjunction with an increased ferritin level and is generally confirmed with a liver or bone marrow biopsy.
External Testicular Insults
Trauma. - The patient may have a history of direct traumatic injury. Testicular torsion sometimes is associated with a "bell-clapper" abnormality in which the testes lie horizontally because of incomplete closure of the surrounding tissues.
Mumps Orchitis. - In patients with postpubertal mumps, a 25% risk of orchitis exists. More than 50% of those with orchitis will be infertile. Increased FSH concentrations and oligospermia or azoospermia are present. Mumps orchitis can progress to produce low testosterone and high LH levels in some men.
Radiation Treatment or Chemotherapy. - With irradiation or chemotherapy, testicular exposure can occur from treatment of another disease or inadvertently. A dose-dependent recovery potential and variable Leydig cell dysfunction have been noted. Pretreatment sperm banking is possible if future "fertility" is desired and sperm counts are normal.
Autoimmune Syndromes
Anti-Leydig cell antibody-associated disorders or conditions associated with anti-sperm antibodies are autoimmune syndromes related to hypogonadism. These syndromes are poorly characterized, and further research is needed to determine diagnostic criteria and possible treatment options.
Sertoli Cell Only Syndrome
The absence of germ cells in patients with small testes, high FSH levels, azoospermia, and normal testosterone levels should suggest the presence of Sertoli cell only syndrome. The diagnosis can be made only by testicular biopsy. The cause is currently unknown.
Hypogonadotropic Hypogonadism
The condition of hypogonadotropic hypogonadism is generally associated with the following findings:
Low or low-normal FSH level relative to testosterone
Low or low-normal LH level relative to testosterone
Low testosterone level
Kallmann's Syndrome
Classic Kallmann's syndrome is a congenital disorder inherited as an X-linked recessive trait manifesting as prepubertal hypogonadism with an incidence of about 1 in 10,000 male births. Low testosterone levels are present because of an impaired release of LH and FSH as a result of variable GnRH deficiency. LH and FSH are released in response to priming followed by stimulation with GnRH. The gene on the X chromosome for classic Kallmann's syndrome and associated anosmia has been identified and cloned (21). Autosomal recessive and autosomal dominant variants of hypogonadotropic hypogonadism also exist and are referred to as idiopathic hypogonadotropic hypogonadism.
Classically, Kallmann's syndrome is associated with anosmia as a result of defective development of the olfactory tract in the brain. The GnRH-containing neurons originate in the developing olfactory tract and therefore do not develop properly in this syndrome (5). This defective development of the olfactory tract can be diagnosed by MRI scanning. In some cases, other defects such as cerebellar dysfunction, cleft palate, and congenital deafness are present (22). Cryptorchidism may occur because gonadotropins contribute to normal testicular descent. The prepubertal testes in patients with Kallmann's syndrome tend to be larger than in patients with Klinefelter's syndrome and are appropriate for age up to puberty, inasmuch as normal initial amounts of germinal tissue are present. Partial pubertal development may be present in patients with partial defects; thus, Kallmann's syndrome may be difficult to distinguish from delayed puberty up through the teenage years. Once a patient with Kallmann's syndrome has been identified, other family members at risk (on the basis of mode of inheritance) should be assessed, if possible.
Other Related Syndromes
Congenital hypogonadotropic syndromes are associated with secondary hypogonadism and other somatic findings. Prader-Willi syndrome is characterized by hypogonadism, short stature, mental retardation, hypotonia at birth, and obesity. Laurence-Moon-Bardet-Biedl syndrome is an autosomal recessive trait characterized by mental retardation, retinitis pigmentosa, polydactyly, and hypogonadism. These syndromes may be due to a hypothalamic deficiency of GnRH.
Fertile Eunuch Syndrome
Hypogonadotropic hypogonadism in patients who have modest FSH secretion and selective LH deficiency is known as the fertile eunuch syndrome. Fertility may be present in some of these patients.
Pituitary Disorders
Acquired hypogonadotropic hypogonadism may indicate the presence of pituitary insufficiency or a pituitary tumor. Unless the reason for the pituitary defect is clear, imaging studies of the pituitary gland are indicated to determine whether a pituitary tumor is present. Hypothalamic tumors, metastatic tumors, granulomas, abscesses, and hemochromatosis may also be discovered.
Hyperprolactinemia is a potential cause of hypogonadotropic hypogonadism and generally manifests with a low libido and impotence. A prolactin level should be determined in men with acquired hypogonadotropic hypogonadism. High prolactin levels are usually associated with a prolactinoma, but certain medications may also cause hyperprolactinemia.
Hypogonadotropic hypogonadism from pituitary disease may also occur with granulomatous and infiltrative disorders, cranial trauma with or without stalk transection, irradiation, and hypophysitis.
Hemochromatosis
See earlier discussion in Hypergonadotropic Hypogonadism section.
Serious Illness, Acquired Immunodeficiency Syndrome, and Stress
Transient hypogonadotropic hypogonadism may occur in patients with serious disorders or malnutrition (23). Acquired immunodeficiency syndrome (AIDS) may be associated with low testosterone levels and generally low gonadotropin levels (consistent with hypothalamic-pituitary involvement). In some patients with AIDS, gonadotropin levels are increased (consistent with testicular disease) (24).
Aging
Considerable controversy exists over the concept of a male climacteric (25). Growing evidence indicates that some aging men have reduced production of testosterone associated with decreased libido, impotence, decreased growth of body hair, decreased muscle mass, increased risk of myocardial infarction (26), and decreased bone mass in conjunction with osteoporosis. Some early studies indicated that the problem may be related to coexisting conditions, but more recent evidence supports the view that an age-related decline in testicular function may occur with associated symptoms and often responds to testosterone replacement therapy (27,28). Measurements of free testosterone or SHBG with total testosterone are usually needed to demonstrate the abnormality. Often the FSH and LH levels are mildly increased, an indication that a primary testicular disorder may be present in conjunction with a secondary abnormality in LH burst frequency (29). Dynamic testing may disclose more subtle abnormalities of hypothalamic function. Data from long-term research studies are desperately needed to clarify the criteria for therapy considerations in aging men. Currently, men with symptomatic hypogonadism and clearly low testosterone levels (free or total, in consideration of SHBG) are potential candidates for therapy, although no specific recommendations can be given.
Short-term research studies have demonstrated improved lean body mass, increased hematopoiesis, decreased low-density lipoprotein (LDL) levels with a constant LDL to high-density lipoprotein (HDL) ratio, improved libido, and improved well-being in men with low testosterone levels after treatment with testosterone. Generally, prostate size does not change in comparison with otherwise normal men, but prostate-specific antigen (PSA) levels have been found to increase in some men (30).
★THERAPY
Goals of Therapy
Restore Sexual Function, Libido, Well-Being, and Behavior
Many studies have been done to evaluate the effects of testosterone therapy on sexual function and well-being in men with hypogonadism (31). Impaired sexual behavior and mood disturbances seem to occur below a certain threshold of circulating testosterone levels, and most studies have demonstrated improved function with testosterone replacement.
In studies of testosterone treatment of men with hypogonadism, investigators have found that treatment resulted in increased sexual interest and increased number of spontaneous erections. On psychologic testing, the men with untreated hypogonadism tended to score high on depression, anger, fatigue, and confusion scales. Hormonal replacement diminished most of these traits, but although the depression score improved, it remained more of a problem in men with hypogonadism than in male control subjects (32). Further long-term studies are clearly needed in this area to establish definite criteria for therapy and response in borderline cases.
With the onset of hypogonadism before puberty, an initial low dose of testosterone should be used to avoid adverse psychologic effects and aggressive behavior.
Produce and Maintain Virilization
Secondary sex characteristics such as increased muscle mass, beard growth, growth of pubic and axillary hair, and phallus growth improve with testosterone therapy.
Optimize Bone Density and Prevent Osteoporosis
In elderly male nursing home residents, the incidence of hip fracture was between 5 and 15% (33). Of those residents who had sustained a prior hip fracture, 66% were found to have hypogonadism (serum testosterone levels less than 300 ng/dL). Hypogonadism was present in up to 20% of men with vertebral crush fractures, even though many of the men did not have other clinical features of hypogonadism. In adolescent male patients with hypogonadotropic hypogonadism, testosterone therapy increases bone mineral density in comparison with that in male patients with hypogonadism not receiving testosterone (34,35). In men with prepubertal-onset hypogonadotropic hypogonadism, however, diminished bone mass may be only marginally improved by testosterone replacement (36).
Possibly Normalize Growth Hormone Levels in Elderly Men
In comparison with normal men, those with hypogonadism have significantly reduced mean growth hormone pulse amplitude but normal pulse frequency. Patients with adult-onset growth hormone deficiency also have increased cardiovascular mortality (37). Testosterone treatment results in a significant increase in 24-hour mean serum growth hormone and mean growth hormone pulse amplitude. Perhaps testosterone has an important role in the control of growth hormone secretion in adulthood, and therapy may have a positive clinical influence (38). No specific recommendations on this issue are possible until further research clarifies the potential risks and benefits of therapy.
Potentially Affect the Risk of Cardiovascular Disease
Orally administered alkylated androgens are nonaromatizable and result in increased LDL and decreased HDL levels, which may increase cardiovascular risk (18,39,40). Unlike orally administered alkylated androgen preparations, testosterone is aromatized to estrogen. In men with hypogonadism treated with replacement doses of testosterone, total cholesterol and LDL levels may modestly decrease in conjunction with little change in HDL; thus, investigators have speculated that the risk of cardiovascular disease may be higher in men with hypogonadism not receiving testosterone replacement (41). Testosterone replacement therapy in men is not associated with major adverse lipid changes (42); in fact, endogenous testosterone and administration of exogenous testosterone may lower the atherogenic Lp(a) lipoprotein levels (43). Other studies suggest that testosterone replacement in men with hypogonadism may be associated with adverse lipid effects, and yet other studies have reported indeterminate findings (25).
Other cardiovascular effects apart from changes in lipids may be attributable to testosterone replacement therapy. A potential risk of testosterone therapy is the propensity of testosterone to increase platelet aggregation and thrombogenicity (44).
Currently, whether testosterone replacement therapy in men with hypogonadism increases, decreases, or has a neutral effect on cardiovascular risk remains uncertain. Long-term prospective research must be conducted to assess the role of endogenous testosterone and testosterone replacement therapy on cardiovascular risk in men. No specific recommendations on this issue are possible until further research clarifies the potential risks and benefits of therapy.
Restore Fertility in Cases of Hypogonadotropic Hypogonadism
See subsequent sections on therapy for hypogonadotropic hypogonadism.
Contraindications to Testosterone, GnRH,
and Gonadotropin Therapy
Testosterone replacement, pulsatile GnRH therapy, and gonadotropin therapy are contraindicated in men with prostate cancer or male breast cancer. Treatment with these medications can stimulate tumor growth in androgen-dependent neoplasms. Careful examination of the male breast and prostate is required initially and at follow-up visits. In addition to prostate examination, baseline and follow-up PSA levels should be determined in older men at increased risk for prostate cancer. Sleep apnea and hyperviscosity states are relative contraindications to the use of testosterone therapy.
Testosterone Therapy in Adult Male Patients
With Hypogonadism
Ideally, testosterone therapy should provide physiologic range testosterone (between 300 and 1,200 ng/dL) and physiologic range dihydrotestosterone and estradiol levels, which would allow optimal virilization and normal sexual function. Testosterone therapy is used in the male patient with hypogonadism who is not interested in fertility or not able to achieve fertility. In late teenage male patients with delayed puberty, testicular size should be monitored for evidence of onset of puberty. In this setting, testosterone therapy should be withdrawn to determine whether spontaneous puberty will occur.
The following preparations of testosterone may be used:
Long-acting intramuscular preparations
Short-acting intramuscular preparations
Pellets
Scrotal patches
Transdermal patches
Orally administered testosterone is quickly metabolized by the liver and cannot achieve sufficient blood levels over time to be useful. The orally administered alkylated androgen preparations currently available in the United States are generally not recommended because of poor androgen effects, adverse lipid changes, and hepatic side effects, such as hemorrhagic liver cysts, cholestasis, and hepatocellular adenoma (18). In Europe, testosterone undecanoate may be a more acceptable oral alternative, but erratic testosterone levels, frequent dosing, high dihydrotestosterone levels, and occasional gastrointestinal side effects may limit the usefulness of this preparation should it become available in the United States. Testosterone pellets are sometimes used, and further study may prove them to be suitable for many men. For patients with hypogonadotropic hypogonadism wishing fertility, hCG with or without human menopausal gonadotropin (FSH) or pulsatile GnRH therapy and hCG with or without assisted reproduction are options.
Parenteral Testosterone Preparations
Testosterone enanthate and testosterone cypionate are long-acting testosterone esters suspended in oil to prolong absorption. Peak levels occur about 72 hours after intramuscular injection and are followed by a slow decline during the subsequent 1 to 2 weeks (45).
For complete androgen replacement, the regimen should be between 75 and 150 mg of testosterone enanthate or cypionate administered intramuscularly every 7 to 10 days, which will allow relatively normal levels of testosterone throughout the time interval between injections (46). Longer time intervals are more convenient but are associated with greater fluctuations in testosterone levels. Higher doses of testosterone produce longer-term effects at the expense of higher peak levels and wider swings between peak and nadir circulating testosterone levels; the result is fluctuating symptoms in many patients (47).
The use of 100 to 200 mg every 2 weeks is a reasonable compromise. Use of 300-mg injections every 3 weeks is associated with wider fluctuations of testosterone levels and is generally inadequate to ensure a consistent clinical response. With use of these longer-interval regimens, many men will have pronounced symptoms during the week preceding the next injection. In such instances, a smaller dose at closer intervals should be tried. As a guide, testosterone levels should be above the lower limit of normal, in the range of 250 to 300 ng/dL, just before the next injection (48).
When full androgen replacement is not required, lower doses of testosterone are used. One such category includes adult male patients with prepubertal onset of hypogonadism who are going through puberty for the first time on therapy and who often may require psychologic counseling, especially when a spouse is involved as well. In these patients, testosterone therapy should be begun at 50 to 100 mg every 3 to 4 weeks with a gradual increase during subsequent months, as tolerated, up to full replacement within 1 year. Men with appreciable benign prostatic hypertrophy who have hypogonadism and symptoms may be given 50 to 100 mg every 2 weeks as an initial regimen and maintained on this dosage with careful monitoring of urinary symptoms and prostate examinations; therapy can be withdrawn if necessary.
Attaining full virilization in the patient with hypogonadism may take as long as 3 to 4 years. Follow-up intervals should be between 4 and 6 months to monitor progress, review compliance, and determine whether any complications or psychologic adjustment problems are present. Often, patients can learn how to administer their own injections. A spouse or significant other may also be instructed in this technique.
Transdermal Testosterone Therapy
Transdermal Testosterone Delivery System: Normal Skin. - A testosterone patch with permeability enhancement allows testosterone delivery through normal skin. Daily evening application generally results in normal-range testosterone levels, which mimic the normal diurnal changes in testosterone in normal men. In contrast to the situation with use of the scrotal patch, dihydrotestosterone levels remain within the normal range (49). Estradiol and bioavailable testosterone levels also remain within the normal range. Skin irritation may be a problem in some patients. Therapy consists of two patches applied to normal skin. As with scrotal patches, treatment is more expensive than injections, but convenience of use, maintenance of normal diurnal testosterone levels, and elimination of office visits for injections may make this form of treatment useful in many patients.
Scrotal Patch Testosterone Delivery System. - Scrotal testosterone patches are available in 40 and 60 cm2 sizes, which deliver, respectively, 4 and 6 mg of testosterone daily. The patch is applied to the scrotal skin after preparation of the scrotum with dry shaving. The patch is nonadhesive, and a new patch is applied each morning. The testosterone levels mimic the diurnal rhythm present in normal men. Testosterone levels are generally maintained in the normal range and are generally tolerated well. Levels should be assessed in the morning before application to ensure that the level is above the lower limit of the normal range at the nadir. If the scrotum is small or the skin surface is abnormal, absorption may be limited. Because genital skin contains high concentrations of 5a-reductase, the dihydrotestosterone levels in treated patients increase initially but may return to normal in some men. In most men treated with the scrotal patch, however, these levels remain higher than normal (50). The HDL:cholesterol ratio in treated patients does not change significantly from before to after therapy (51). The long-term potential effects of increased levels of dihydrotestosterone are unknown at this time, and careful monitoring of prostate growth is recommended. Further research may clarify any possible adverse effects of such increased levels occurring in men who receive this type of therapy. The cost of using the scrotal patch is greater than for testosterone injections, but the convenience of use may make this therapeutic option acceptable for many patients.
Side Effects of Testosterone Therapy
Periodic follow-up of patients receiving testosterone therapy is recommended. During the first year of therapy, the patient should have the progress and the side effects monitored at 3- to 4-month intervals. Examination of the prostate should be done routinely. PSA levels should be determined annually in older men receiving testosterone replacement therapy, and the hematocrit should be determined at least yearly. An initial lipid profile should be recorded, and a follow-up profile should be done after 6 to 12 months of therapy.
Testosterone, and especially dihydrotestosterone, stimulates the growth of the prostate and seminal vesicles. In a study that assessed the effect of exogenous testosterone administration by patch or by injection on the serum levels of PSA and prostate-specific membrane antigen in men with hypogonadism, the results demonstrated no correlation with therapy and thus no testosterone dependence of PSA or prostate-specific membrane antigen (52). Testosterone treatment of men with hypogonadism also resulted in growth of the prostate and seminal vesicles, but this growth did not exceed the volumes expected in normal men (53). No clear relationship has been established between testosterone replacement therapy and prostate cancer, although anecdotal reports have been published (54). Long-term studies are needed to clarify this issue.
Gynecomastia may result from the aromatization of testosterone to estradiol and changes in SHBG levels. The use of aromatase inhibitors, such as testolactone, or surgical therapy may be considered for some patients.
Supraphysiologic levels of testosterone stimulate the bone marrow production of erythrocytes. The result is an increased hematocrit with the possibility of hyperviscosity side effects (55).
Lipid disturbances in testosterone-treated male patients are generally not a problem because of the aromatization of testosterone to estradiol. The HDL:total cholesterol ratio generally remains constant. Anabolic steroids that are not aromatized increase LDL and lower HDL levels and could increase cardiovascular risk.
Sleep apnea may also be a problem in some men, and testosterone therapy should be discontinued until the sleep apnea problem can be adequately addressed (56).
Gonadal Stimulation in Hypogonadotropic Hypogonadism
Because gonadotropin or GnRH therapy is effective only in hypogonadotropic hypogonadism, this diagnosis must be firmly established before consideration of therapy. Although these agents may also be used to induce puberty in boys and to treat androgen deficiency in hypogonadotropic hypogonadism, the major use of these preparations is in the initiation and maintenance of spermatogenesis in hypogonadotropic men who desire fertility.
Gonadotropin Therapy in Androgen Deficiency[略]
Gonadotropin Therapy for Induction of Spermatogenesis[略]
GnRH Therapy[略]
Other Treatment Considerations[略]
Antiestrogen Therapy in Oligospermia[略]
Assisted Reproductive Technology[略]
Pituitary Tumors[略]
Gynecomastia[略]
Psychologic Counseling[略]
★SUMMARY
The major objectives of the initial assessment are to distinguish primary gonadal failure (hypergonadotropic hypogonadism with low testosterone and increased FSH and LH levels) from hypothalamic-pituitary disorders (hypogonadotropic hypogonadism with low testosterone and low to normal FSH and LH levels) and to make a specific diagnosis. The initial clinical manifestations may vary, depending on whether the onset of the disorder was prepubertal or postpubertal. Men with hypogonadotropic disorders may achieve fertility with gonadal stimulation. Men with hypergonadotropic disorders are treated with testosterone to achieve virilization and are usually, but not invariably, incapable of achieving fertility.
History and Physical Examination[略]
Laboratory and Ancillary Evaluation[略]
Diagnosis and Treatment
An overall summary of clinical and laboratory findings, potential diagnoses, and recommended evaluation or treatment strategies in adult male patients with hypogonadism is presented in Table 1.
*FSH=follicle-stimulating hormone; GnRH=gonadotropin-releasing hormone; hCG=human chorionic gonadotropin; hMG=human menopausal gonadotropin; ICSI=intracytoplasmic sperm injection; IUI=intrauterine insemination; IVF=in vitro fertilization; LH=luteinizing hormone; MRI=magnetic resonance imaging; N=normal; SHBG=sex hormone-binding globulin; T=testosterone.
Table 1
Summary of Findings, Potential Diagnoses, and Recommended Strategies in Adult Male Patients with Hypogonadism*
Testicular Size FSH LH Semen Analysis Diagnosis Evaluation or Treatment Not Palpable Azoospermia Anorchism Surgical Exploration Not Palpable Azoospermia Bilateral Cryptorchidism Surgical Exploration <5 mL Azoospermia, oligospermia Kallman's syndrome, hypogonadotropic hypogonadism T to virilize; hCG ± hMG (or FSH) or GnRH for spermatogenesis <5 mL Azoospermia Klinefelter's syndrome, other hypogonadotropic syndromes Karyotype to confirm; T to virilize 8-15 mL N N Azoospermia, oligospermia Germinal damage; toxins, idiopathic Fertility: IVF with ICSI(?) 10-20 mL Oligospermia Adult acquired hypogonadotropic hypogonadism Pituitary MRI; prolactin. Treat pituitary disorder if present; otherwise treat as Kallman's syndrome 10-20 mL Variable Senescence T if symptomatic with low T 15-20 mL N or N N Oligospermia Varicocele, drugs, idiopathic Fertility: varicocele repair if significant varicocele present. Optimize wife; IVF with ICSI Variable Phenotype Variable T receptor defects, Reifenstein's syndrome Variable (depending on degree): medical or surgical therapy 20-30 mL N N N Azoospermia Obstruction Fertility; surgical repair; IUI, IVF with ICSI
Normal testicular size is 20-30 mL. Testicular size is used here as a clinical finding to help narrow the differential diagnosis. Some variation beyond the listed ranges may exist for a specific condition. Use of this variable is optional; the diagnosis should be based on the total clinical picture.
Because of changes in SHBG levels, total testosterone may be in the normal range in the setting of low testosterone production. An SHBG level or free testosterone should be used in this setting to determine whether treatment options should be considered.
CONCLUSION
The recognition, evaluation, and treatment of hypogonadism in the male patient are often dismissed by the patient and overlooked by the physician. The symptoms and signs of hypogonadism should be identified through appropriate questioning of the patient and a directed physical examination. Hormonal and ancillary testing should be performed in a cost-efficient and clinically appropriate manner to allow pertinent treatment considerations. Replacement therapy can often enable the patient to function in a more normal manner and decrease the risk of future problems with fertility, mood disturbances, fatigue, impaired virilization, and osteoporosis. Further studies are needed to determine the influence of testosterone replacement on cardiovascular risk. Of importance, these guidelines demonstrate the need for meaningful, long-term studies on hypogonadal disorders in general and in aging men in particular. The ultimate goals are to improve not only the duration but also the quality of life and to allow people to reach their full potential regardless of age.
REFERENCES[略]
■AACE On-Line: Sexual Dysfunction Guidelines[1998] AACE Clinical Practice Guidelines For The Evaluation and Treatment of Male Sexual Dysfunction
Developed by
The American Association of Clinical Endocrinologists
and The American College of Endocrinology
© 1998, AACE
Male Sexual Dysfunction Taskforce
[略]
TREATMENT OF SEXUAL DYSFUNCTION
[略]
Psychologic Treatment[略]
Medical Treatment[略]
●Hormonal Treatment
Benign prostatic hyperplasia, prostate cancer, sleep apnea, and polycythemia must be evaluated before and after initiation of testosterone therapy. A baseline prostate-specific antigen level should be determined before treatment; if this value is even slightly increased, the patient should be referred to a urologist for a prostate evaluation. Any patient treated with replacement androgens should be reassessed within a few months after initiation of therapy and then at 6- to 12-month intervals to ensure that clinical problems have not appeared or worsened during such treatment. The presence of prostate cancer is a contraindication to androgen therapy, whereas sleep apnea, peripheral edema, polycythemia, and benign prostatic hyperplasia are relative contraindications that may respond to adjustments in the medication or specific treatments (use of continuous positive-airway pressure or weight reduction).
Testosterone replacement for the treatment of hypogonadism may also correct sexual dysfunction, unless the patient has other comorbid illnesses. For decades, the standard has been a depot intramuscular injection of testosterone enanthate or cypionate every 2 or 3 weeks (200 mg or 300 mg, respectively). Smaller dosages and more frequent injections, however, are better at maintaining circulating testosterone in the normal range (that is, 50 to 150 mg of testosterone enanthate or cypionate intramuscularly at 7- to 14-day intervals). An alternative approach is to administer 100 mg on days 1, 11, and 21 of each month, while allowing some flexibility of injection days. If testosterone levels are measured, they should be in the normal range just before the next injection. Currently available tablets for oral administration have generally not been used because of potential liver toxicity. A newer oral tablet, testosterone undecanoate, has been used for more than a decade in Europe but has not yet been approved for use in the United States. Although the safety is not questioned, multiple daily doses are required and the absorption is erratic. Other orally and sublingually administered tablets are being evaluated. Implantable testosterone pellets, which are used in other countries, and other forms of intramuscular testosterone preparations are also being evaluated.
Testosterone scrotal and nonscrotal patches have now been approved by the Food and Drug Administration (FDA). Testosterone absorption is greater through scrotal skin. The scrotal patch was the first to be introduced. These patches are placed on the scrotal skin and are changed daily, in the morning. For many patients, weekly shaving of the scrotum is necessary. The patch increases testosterone levels to the normal range, which remain stable. Because 5a-reductase in scrotal skin is high, the dihydrotestosterone (DHT) level in serum is quite high. The role of DHT is currently being investigated. It may have little biologic activity because it is largely bound to sex hormone binding globulin.
The nonscrotal patch, applied daily in the evening, may be worn in various sites on the skin. The manufacturer recommends that it not be used over bony prominences. The levels of testosterone increase during the nighttime hours, a pattern mimicking the body's normal diurnal variation. The levels remain stable in the middle of the normal range, and the DHT levels remain normal. Contact dermatitis at the site of application is seen in approximately a third of the patients. Some patients may control this skin reaction with triamcinolone cream, but 10% of patients may have to discontinue the use of testosterone patches.
With any form of testosterone treatment, the patient may have a slow and steady increase in libido and erectile capacity during a course of months. If no improvement is noted after 3 months, the hormone deficiency may not be the only cause of the sexual dysfunction. A comorbid medical illness might also be present, or perhaps performance anxiety is dominant.
The hypothalamic-pituitary-gonadal axis has been shown to decrease functioning temporarily after acute medical events or surgical procedures; this action can cause low gonadotropin and testosterone levels. Such a temporary decrease in testosterone levels may also occur as a result of less serious circumstances, such as anxiety, alcohol excess, multiple medications, or uncontrolled diabetes. Patients with these causes are less likely to respond to testosterone replacement. Stimulation of gonadotropins with clomiphene citrate and the subsequent increase in testosterone levels emphasize the functional and reversible nature of this phenomenon; short-term use of clomiphene citrate may help some patients. Occasionally, low testosterone levels are due to suppressed gonadotropins attributable to an increased prolactin level. This situation can be reversed by treatment with bromocriptine or pergolide. If increased prolactin is due to a psychotropic drug, however, withdrawing or switching the medication may be all that is needed.
Treatment of other endocrine disorders, such as hypothyroidism or hyperthyroidism, reverses the libido or erectile dysfunction that accompanies these and other hormonal disorders. Uncontrolled diabetes mellitus may respond to improved plasma glucose control, especially in patients with recently diagnosed diabetes. Even patients with diabetes who have been afflicted for more than 10 years may respond to better control if major neuropathy is absent. Hypogonadism also seems to be especially prevalent in patients with diabetes, and many respond to testosterone treatment.
Current Nonspecific Treatments for Erectile Dysfunction
Some patients do not respond to the aforementioned corrective measures and need nonspecific therapy (Table 2). This scenario might especially exist in older men and those with numerous medical risk factors. The major options to consider at the present time are yohimbine tablets, vacuum pump devices, venous constriction rings, intracorporeal injections of various chemicals, intraurethral drug suppositories, intrapenile arterial or venous surgical procedures, penile implants, or, the latest treatment, orally administered phosphodiesterase inhibitors. Trials with sublingually administered apomorphine and vasodilators are ongoing.
Table 2
The Most Commonly Used Nonspecific
Treatments for Erectile Dysfunction
Yohimbine tablets
Venous constriction rings
Vacuum devices
Pharmacologic erection program
Intracorporeal injections
Papaverine-phentolamine
Papaverine-phentolamine-prostaglandin E1
Prostaglandin E1
Potassium channel openers (?)
Intraurethral suppositories
Prostaglandin E1
Penile microvascular arterial bypass operation
Penile venous ligation surgical procedure
Penile implants
Flexible rods
Inflatable cylinders
Orally administered phosphodiesterase inhibitors
Sildenafil
[略]
CONCLUSION[略]
REFERENCES AND SUGGESTED READING[略]
APPENDIX[略]
●総説記事・文献
●ニュース・トピックス
●リンク＆リソース
■リンク
●日本
●日本性機能学会 - 学会案内。 （財）性の健康医学財団 日本アンドロロジー学会[男性不妊症]
●海外
●性機能・性医学関連学会 ESDA - European Sexual Dysfunction Alliance(欧州性機能学会) - http://www.esda.eu.com/home.htm ISSIR - International Society for Sexual and Impotence Research - http://www.issir.org/ - ISSIR Newsletter No.10: Epidemiology of Erectile Dysfunction: A Worldwide prevalence overview[pdf 32p:] 23-28p, Apr.2003 - Int J Impot Res.[隔月刊]機関誌〜抄録公開 CIEF - Consortium for Improvement in Erectile Function - http://www.erectilefunction.org/; ED関連専門家主体の団体 ED文献ライブラリーではレビュー、一般文献などわかりやすくリスト&Link SMSNA - Sexual Medicine Society of North America, Inc. - http://www.smsna.org/ ●アンドロロジー(男性不妊症)・アンドロポース(男性更年期)学会 ISA - International Society of Andrology - http://www.andrology.org/ Canadian Andropause Society - http://andropausesociety.ca/mainEG.html ●リンク集 Google: Sexual Dysfunctions Google: Impotence Google: Impotence>Testosterone and Hormone Replacement Hypogonadism hub - 資料集リンク
■MEDLINEplus: Impotence Contents of this page:
News
From the NIH
General/Overviews
Clinical Trials
Coping
Diagnosis/Symptoms
Pictures/Diagrams
Research
Specific Conditions/Aspects
Treatment
Dictionaries/Glossaries
Directories
Organizations
Statistics
Search MEDLINE for recent research articles on
・General
・Therapy
You may also be interested in these MEDLINEplus related pages:
・Men's Health
・Seniors' Health
・Sexual Health●Latest News
Viagra Tested for Altitude Sickness (09/15/2003, United Press International)●From the National Institutes of Health
Erectile Dysfunction (National Kidney and Urologic Diseases Information Clearinghouse)
Also available in:
Spanish●General/Overviews
Endocrinology and Impotence (Erectile Dysfunction) (Endocrine Society)
Impotence: Learning the Causes and What You Can Do (American Academy of Family Physicians) - multi-page document
Also available in:
Spanish●Clinical Trials
ClinicalTrials.gov: Impotence (National Institutes of Health)
Clinical Trials: Erectile Dysfunction (CenterWatch, Inc.) - industry-sponsored clinical trials●Coping
JAMA Patient Page: Sexual Dysfunction -- Silence About Sexual Problems Can Hurt Relationships (American Medical Association)
Where to Seek Professional Help: Sexuality and Cancer (American Cancer Society)●Diagnosis/Symptoms
Testosterone Test (American Association for Clinical Chemistry)●Pictures/Diagrams
Overview of the Male Anatomy (University of Utah, Health Sciences Center)●Research
FDA Approves New Drug for Treatment of Erectile Dysfunction in Men (Food and Drug Administration)
Nerve Grafting Restores Erectile Function After Prostatectomy: New Hope for Sex Life After Prostate Removal (American Cancer Society)
Regular Cycling Can Improve Sexual Function in Men with Heart Failure (American Heart Association)
Risk of Erectile Dysfunction Similar for Different Prostate Cancer Treatments (American Cancer Society)
Sexual Function in Men Older Than 50 Years of Age (American College of Physicians)●Specific Conditions/Aspects
Erectile Dysfunction and Diabetes: Many Possible Solutions (Mayo Foundation for Medical Education and Research)
Male Sexual Problems (American Association for Marriage and Family Therapy)
Patient's Guide to Low Testosterone (Endocrine Society, Hormone Foundation)
Peyronie's Disease (National Kidney and Urologic Diseases Information Clearinghouse)
What Is Peyronie's Disease? (Mayo Foundation for Medical Education and Research)●Treatment
Erectile Dysfunction - Viagra (Patient Education Institute) - requires Flash plug-in
Also available in:
Spanish
FDA Assesses Irregularities Involving the Handling of Certain Unapproved Imported Viagra Products (Food and Drug Administration)
Testosterone Replacement Therapy: Effective Treatments Are Available (Mayo Foundation for Medical Education and Research)
Viagra: Proper Use Can Restore Erections (Mayo Foundation for Medical Education and Research)●Dictionaries/Glossaries
Erectile Dysfunction: Glossary (American Foundation for Urologic Disease)
Also available in:
Spanish●Directories
Directory of Kidney and Urologic Diseases Organizations (National Kidney and Urologic Diseases Information Clearinghouse)
TherapistLocator Directory of the United States (American Association for Marriage and Family Therapy)●Organizations
American Foundation for Urologic Disease
National Institute of Diabetes and Digestive and Kidney Diseases●Statistics
Kidney and Urologic Disease Statistics for the United States (National Kidney and Urologic Diseases Information Clearinghouse)
Interactive Tutorial
View slideshow on:
Erectile Dysfunction - Viagra
Page last updated: 16 September 2003
Topic last reviewed: 14 May 2003
●MEDLINEplus: Sexual Health (General)
Contents of this page: News General/Overviews Diagnosis/Symptoms Pictures/Diagrams Specific Conditions/Aspects Dictionaries/Glossaries Directories Lists of Print Publications Organizations Statistics Children Men Seniors Teenagers Women Search MEDLINE for recent research articles on ・Sexual Health (General) You may also be interested in these MEDLINEplus related pages: ・Female Sexual Dysfunction ・Infertility ・Male Genital Disorders ・Reproductive Health (General) ・Teen Sexual Health ・Men's Health ・Sexual Health ・Wellness and Lifestyle ・Women's Health●Latest News
Sex Life Normal for Women with Rebuilt Vagina (09/12/2003, Reuters Health)●General/Overviews
Sexual Health: Common Questions for Couples (Mayo Foundation for Medical Education and Research)
Sexuality and Sexual Problems (American College of Obstetricians and Gynecologists)●Diagnosis/Symptoms
Estrogen Tests (American Association for Clinical Chemistry)
Testosterone Test (American Association for Clinical Chemistry)●Pictures/Diagrams
Atlas of the Body: Female Reproductive Organs (American Medical Association)●Specific Conditions/Aspects
Compulsive Sexual Behavior (Mayo Foundation for Medical Education and Research)
Infidelity (American Association for Marriage and Family Therapy)
Sexual Activity and Heart Disease or Stroke (American Heart Association)
Sexuality and Reproductive Issues (PDQ) (National Cancer Institute) - Sexual side effects from cancer and cancer treatment
Also available in:
Spanish●Dictionaries/Glossaries
Definitions of Sexually Related Health Terminology (Sexuality Information and Education Council of the United States)
Also available in:
Spanish
Sexual Health Glossary (American Social Health Association)●Directories
TherapistLocator Directory of the United States (American Association for Marriage and Family Therapy)●Lists of Print Publications
Sexuality Education in the Home (Sexuality Information and Education Council of the United States)
Sexuality In Middle And Later Life (Sexuality Information and Education Council of the United States)●Organizations
American Association for Marriage and Family Therapy
Sexuality Information and Education Council of the United States●Statistics
At-A-Glance: The Surgeon General's Call to Action to Promote Sexual Health and Responsible Sexual Behavior (Surgeon General)
JAMA Patient Page: Sexual Dysfunction -- Silence About Sexual Problems Can Hurt Relationships (American Medical Association)●Children
Discussing Birds and Bees: Start When Your Kids are Very Young (Mayo Foundation for Medical Education and Research)
Sexual Behavior in Children: What's Normal? (Mayo Foundation for Medical Education and Research)
Sexual Stereotypes and Sexual Orientation (American Academy of Pediatrics)
Syndromes of Abnormal Sex Differentiation: A Guide for Patients and Their Families (Johns Hopkins University, School of Medicine)
When Gender Identities Become Confused (American Academy of Pediatrics)●Men
Cancer Treatment's Effects on Male Sexuality (American Cancer Society)
Male Sexual Problems (American Association for Marriage and Family Therapy)
Male Sexuality After Cancer (Mayo Foundation for Medical Education and Research)
Patient's Guide to Low Testosterone (Endocrine Society, Hormone Foundation)●Seniors
Intimacy and Aging: Tips for Sexual Health and Happiness (Mayo Foundation for Medical Education and Research)
Sexuality in Later Life (National Institute on Aging)●Teenagers
!Enterate! Your Guide to Safer Sex (Henry J. Kaiser Family Foundation)
Also available in:
Spanish●Women
Midlife Sexuality and Women: Getting Better with Age (Mayo Foundation for Medical Education and Research)
Women and Testosterone? (Mayo Foundation for Medical Education and Research)
Page last updated: 14 September 2003
Topic last reviewed: 27 March 2003
●主要サイト
■AACE.COM: The Official Web Site of The American Association of Clinical Endocrinologists
-http://www.aace.com/; 1991設立、会員4000人 このサイトの特徴は内分泌関連臨床ガイドラインが充実していること。 ●ORGANIZATION ●EDUCATION Regional Meetings 2002 Annual Meeting Highlight[会員限定] ●PUBLICATIONS Endocrine Practice★機関誌−年６回、抄録公開全文要登録 Firs Messenger★会報［隔月刊］ Press Releases AACE Online News[メルマガ, ３週毎] ●CLINICAL INFO★診療ガイドライン AACE Clinical Practice Guidelines The Clinical Research Database Fellows Clinical Corner ●SERVICES The Endocrinology Calendar AACE Membership Directory Endocrinology Employment Media Resource Room★各種広報資料 ●MEMBERS' AREA =========================================
■AACE Online: AACE Clinical Practice Guidelines
●AACE Position Statements [pdf]AACE Statement on WHIMS [pdf]AACE Position: Insulin Resistance Syndrome [pdf]AACE Position: Women's Health Initiative [pdf]Position Statement on Subclinical Hypothyroidism During Pregnancy [pdf]Obesity Position Statement © 1998●肥満症 ●AACE Medical Guidelines for Clinical Practice [pdf]2001 Postmenopausal Osteoporosis - Revised © 2003●骨粗鬆症 [pdf]Growth Hormone Use in Adults and Children © 2003●成長ホルモン [pdf]Male Sexual Dysfunction © 2003●性機能障害 [pdf]Hypogonadism © 2002●性機能障害（testosterone/gnrh） [pdf]Hyperthyroidism and Hypothyroidism © 2002●甲状腺 [pdf]Diabetes Mellitus © 2002- 2002 update●糖尿病 [pdf]2001 Thyroid Carcinoma © 2001●甲状腺腫 [pdf]2001 Hyperandrogenism © 2001 [pdf]Dyslipidemia and Atherogenesis © 2002 [pdf]Clinical Practice for Management of Menopause © 1999 [pdf]Thyroid Nodule © 1996●甲状腺
[1368]●製品 testosterone (Axiron Topical solution [Eli Lilly])
日本語版註）testosterone (Axiron Topical solution [Eli Lilly])
【別名】 【開発元】創製豪Acrux Ltd [DBR_ID]46073-246
【化学名】17-beta hydroxyandrost-4-en-3-one
【承認】FDA申請=3-Sep-2009 - 27-Jan-2010[Acrux Ltd]、FDA承認=23-Nov-2010、米国発売31-Mar-2011[Lilly] ; 【製剤】AXIRON (testosterone) topical solution is available as a metered-dose pump. One pump actuation(1.5mL) delivers 30 mg of testosterone. Each metered-dose pump is supplied with an applicator. 【適応】indicated for replacement therapy in males for conditions associated with a deficiency or absence of endogenous testosterone: (1)Primary hypogonadism (congenital or acquired) (2)Hypogonadotropic hypogonadism (congenital or acquired) 【用法用量】１日１回朝60mg(ポンプ１回30mg定量x2回噴霧)
【作用】Endogenous androgens, including testosterone and dihydrotestosterone (DHT), are responsible for the normal growth and development of the male sex organs and for maintenance of secondary sex characteristics. These effects include the growth and maturation of prostate, seminal vesicles, penis and scrotum; the development of male hair distribution, such as facial, pubic, chest and axillary hair; laryngeal enlargement, vocal cord thickening, alterations in body musculature and fat distribution. Testosterone and DHT are necessary for the normal development of secondary sex characteristics. Male hypogonadism results from insufficient secretion of testosterone and is characterized by low serum testosterone concentrations. Signs/symptoms associated with male hypogonadism include erectile dysfunction and decreased sexual desire, fatigue and loss of energy, mood depression, regression of secondary sexual characteristics and osteoporosis.Male hypogonadism has two main etiologies. Primary hypogonadism is caused by defects of the gonads, such as Klinefelter’s Syndrome or Leydig cell aplasia, whereas secondary hypogonadism is the failure of the hypothalamus (or pituitary) to produce sufficient gonadotropins (FSH, LH). 【特徴】新剤型
【製品情報】www.axiron.com 【添付文書】Axiron -PI
【提携】[16-Mar-2010] Eli LillyはAcruxからAXIRONの全世界独占販売権を獲得。 【EU】
【日本】未開発 【その他】
US Pharmacopeial Commission AMA: United States Adopted Names BIAM --- BIAM -ABC順|BIAM -会社順 NLM: MeSH HOme ---MeSH Online search★
★1368★27/14★11.07.11★054★性腺機能低下治療薬テストステロン局所用液(Axiron - Lilly)/2p●MLリソース：Androgen/男性ホルモン
【日本語版コメント1368〜性腺機能低下治療薬テストステロン局所用液(Axiron - Lilly)】
日本のテストステロン製剤は、錠剤と注射剤のみで、経皮製剤は販売されていない(OTCでは軟膏剤あり)。 例えばエナルモン錠25mg(あすか製薬；メチルテストステロン)の適応は「男子性腺機能不全(類宦官症) 、造精機能障害による男子不妊症 、末期女性性器癌の疼痛緩和，手術不能の乳癌」。→詳細は参考資料●MLリソース：Androgen/男性ホルモンに纏めた。＜日本語版コメント要約＞
・男性の性腺機能低下の治療薬として、腋窩に塗布する局所用テストステロン液Axironが使用できるようになった。
・腋窩に塗布するのは、おそらく皮膚接触により家族や性的パートナーが本剤に曝露するリスクを抑えるため。
・臨床試験では、120日後、84%の患者の血清テストステロン濃度が正常化した（300〜1,050 ng/dL）。
●承認データ：FDA ●FDA Newsroom - FDA Press Releases ●Index to Drug-Specific Information ●2004.5.1 以降 Drugs@FDA
★Drug Name(s) =AXIRON (TESTOSTERONE) FDA Application No. =(NDA) 022504 Active Ingredient(s)=TESTOSTERONE Company =ELI LILLY AND CO Dosage Form/Route =SOLUTION, METERED; TRANSDERMAL Strength =30MG/1.5ML ACTIVATION - Approval Date=11/23/2010[000][Approval]:Label[添付文書]|Letter[承認書]|Review|Summary Review to Acrux Pharma Pty Ltd 申請January 25, 2010 適応Axiron® (testosterone) topical solution for replacement therapy in males for conditions associated with a deficiency or absence of endogenous testosterone. Original Approval or Tentative Approval Date=November 23, 2010 Chemical Type= 3 New formulation Review Classification= S Standard review drug - Approval Date=03/31/2011[002][Labeling Revision]:Label[添付文書]|Letter[承認書]| TO Eli Lilly and Company 申請December 22, 2010 適応the Acrux Pharma Ptd LtdをEli Lillyに変更
●Electronic Orange Book /2011.11.01/
Application Number: N022504 Active Ingredient : TESTOSTERONE Proprietary Name : AXIRON[ELI LILLY AND CO] SOLUTION, METERED; TRANSDERMAL 30MG/1.5ML ACTIVATION Approval Date : Nov 23, 2010 Exclusivity Data : NP Nov 23, 2013 Patent Data : 6299900 Feb 19, 2017 Y U - 1103 6818226 Feb 19, 2017 Y U - 1103 6923983 Feb 19, 2017 Y U - 1103 Application Number: N021543 Active Ingredient : TESTOSTERONE Proprietary Name : STRIANT [ACTIENT PHARMS] TABLET, EXTENDED RELEASE; BUCCAL 30MG Approval Date : Jun 19, 2003 Exclusivity Data : - Patent Data : 6248358 Aug 23, 2019 U - 527 Application Number: N021463 Active Ingredient : TESTOSTERONE Proprietary Name : FORTESTA [ENDO PHARMS] GEL, METERED; TRANSDERMAL 10MG/0.5GM ACTIVATION Approval Date : Dec 29, 2010 Exclusivity Data : NP Dec 29, 2013 Patent Data : 6319913 Nov 9, 2018 U - 490 6579865 Nov 9, 2018 Y Application Number: N021454 Active Ingredient : TESTOSTERONE Proprietary Name : TESTIM [AUXILIUM PHARMS] GEL; TRANSDERMAL 1% (5GM/PACKET) Approval Date : Oct 31, 2002 Exclusivity Data : - Patent Data : 7320968 Jan 18, 2025 U - 843 7608605 Apr 21, 2023 U - 1009 7608606 Apr 21, 2023 U - 1009 7608607 Apr 21, 2023 U - 1009 7608608 Apr 21, 2023 U - 1009 7608609 Apr 21, 2023 U - 1009 7608610 Apr 21, 2023 U - 1009 7935690 Apr 21, 2023 U - 1009 Application Number: N021015 Active Ingredient : TESTOSTERONE Proprietary Name : ANDROGEL [ABBOTT PRODS] GEL, METERED; TRANSDERMAL 1% (1.25GM,2.5GM,5GM/ACTIVATION) Approval Date : Feb 28, 2000[2.5g,5g]Sep 26, 2003[1.25g] Exclusivity Data : 6503894 Aug 30, 2020 U - 490 6503894*PED Mar 1, 2021 Patent Data : - Application Number: N022309 Active Ingredient : TESTOSTERONE Proprietary Name : ANDROGEL [ABBOTT PRODS] GEL, METERED; TRANSDERMAL 1.62% (20.25MG/1.25GM ACTIVATION) Approval Date : Apr 29, 2011 Exclusivity Data : NP Apr 29, 2014 Patent Data : 6503894 Aug 30, 2020 U - 1103 Application Number: N020489 Active Ingredient : TESTOSTERONE Proprietary Name : ANDRODERM [WATSON LABS] FILM, EXTENDED RELEASE; TRANSDERMAL 2.5MG/24HR; 5MG/24HR Approval Date : Sep 29, 1995[2.5mg]May 2, 1997[5mg] Exclusivity Data : x Patent Data : 5152997 Dec 11, 2010 U - 490 5164190 Dec 11, 2010
Appl
NoTE Code RLD Active
IngredientDosage Form;
RouteStrength Proprietary
NameApplicant 承認日 特許 先発権 A083976 Yes METHYLTESTOSTERONE CAPSULE; ORAL 10MG TESTRED VALEANT PHARM INTL Jan 1, 1982前 x x A080767 BP No METHYLTESTOSTERONE TABLET; ORAL 10MG METHYLTESTOSTERONE IMPAX LABS Jan 1, 1982前 x x A084310 BP No METHYLTESTOSTERONE TABLET; ORAL 25MG METHYLTESTOSTERONE IMPAX LABS Jan 1, 1982前 x x A086450 BP No METHYLTESTOSTERONE TABLET; ORAL 10MG ANDROID 10 VALEANT PHARM INTL Jan 1, 1982前 x x A087147 BP Yes METHYLTESTOSTERONE TABLET; ORAL 25MG ANDROID 25 VALEANT PHARM INTL Jan 1, 1982前 x x N020489 Yes TESTOSTERONE FILM, EXTENDED RELEASE; TRANSDERMAL 2.5MG/24HR; 5MG/24HR ANDRODERM WATSON LABS Sep 29, 1995[2.5mg]
May 2, 1997[5mg]2010 x N021015 Yes TESTOSTERONE GEL, METERED; TRANSDERMAL 1% (1.25GM,2.5GM,5GM/ACTIVATION) ANDROGEL ABBOTT PRODS Feb 28, 2000[2.5g,5g]
Sep 26, 2003[1.25g]2021 x N022309 Yes TESTOSTERONE GEL, METERED; TRANSDERMAL 1.62% (20.25MG/1.25GM ACTIVATION) ANDROGEL ABBOTT PRODS Apr 29, 2011 2020 2014 N021463 Yes TESTOSTERONE GEL, METERED; TRANSDERMAL 10MG/0.5GM ACTIVATION FORTESTA ENDO PHARMS Dec 29, 2010 2018 2013 N021454 BX Yes TESTOSTERONE GEL; TRANSDERMAL 1% (5GM/PACKET) TESTIM AUXILIUM PHARMS Oct 31, 2002 2023 x A080911 Yes TESTOSTERONE PELLET; IMPLANTATION 75MG TESTOPEL SLATE PHARMS Jan 1, 1982前 x x N022504 Yes TESTOSTERONE SOLUTION, METERED; TRANSDERMAL 30MG/1.5ML ACTIVATION AXIRON ELI LILLY AND CO Nov 23, 2010 2017 2013 N021543 Yes TESTOSTERONE TABLET, EXTENDED RELEASE; BUCCAL 30MG STRIANT ACTIENT PHARMS Jun 19, 2003 2019 x A090387 AO No TESTOSTERONE CYPIONATE INJECTABLE; INJECTION 100MG,200MG/ML TESTOSTERONE CYPIONATE BEDFORD Jul 15, 2010 x x A040530 AO No TESTOSTERONE CYPIONATE INJECTABLE; INJECTION 200MG/ML TESTOSTERONE CYPIONATE PADDOCK Jan 31, 2005 x x A085635 AO Yes TESTOSTERONE CYPIONATE INJECTABLE; INJECTION 100MG,200MG/ML DEPO-TESTOSTERONE PHARMACIA AND UPJOHN Jan 1, 1982前 x x A040615 AO No TESTOSTERONE CYPIONATE INJECTABLE; INJECTION 100MG,200mg/ML TESTOSTERONE CYPIONATE SANDOZ Aug 10, 2006 x x A040652 AO No TESTOSTERONE CYPIONATE INJECTABLE; INJECTION 200MG/ML TESTOSTERONE CYPIONATE SYNERX PHARMA Dec 11, 2006 x x A086030 AO No TESTOSTERONE CYPIONATE INJECTABLE; INJECTION 200MG/ML TESTOSTERONE CYPIONATE WATSON LABS Jan 1, 1982前 x x N009165 AO Yes TESTOSTERONE ENANTHATE INJECTABLE; INJECTION 200MG/ML DELATESTRYL ENDO PHARM Jan 1, 1982前 x x A040575 AO No TESTOSTERONE ENANTHATE INJECTABLE; INJECTION 200MG/ML TESTOSTERONE ENANTHATE PADDOCK Jun 14, 2006 x x A040647 AO No TESTOSTERONE ENANTHATE INJECTABLE; INJECTION 200MG/ML TESTOSTERONE ENANTHATE SYNERX PHARMA Oct 5, 2009 x x A085598 AO No TESTOSTERONE ENANTHATE INJECTABLE; INJECTION 200MG/ML TESTOSTERONE ENANTHATE WATSON LABS Jan 1, 1982前 x x
●EU承認 ●ema - Human Medcines ●List of Authorized Products (EPARs)★[A-Z 承認品目] ★Intrinsa(testosterone) Sexual Dysfunctions, Psychological - 28/07/2006 Authorised 1. Summary for the public 2. All Authorised Presentations 3. Scientific Discussion 4. Procedural steps taken before authorisation 5. Procedural steps taken and scientific information after authorisation Product Information, please see below Annex I - Summary of product Characteristics Annex IIA - Manufacturing Authorisation Holder responsible for Batch Release Annex IIB - Conditions of the Marketing Authorisation Annex IIIA - Labelling Annex IIIB - Package Leaflet [Name] Intrinsa 300 micrograms/24 hours transdermal patch (Each patch of 28 cm2 contains 8.4 mg testosterone and provides 300 micrograms of testosterone per 24 hours.) [EMA Product number] EMEA/H/C/000634 [Active substance] testosterone [INN or common name] testosterone [Therapeutic area] Sexual Dysfunctions, Psychological [ATC Code] G03BA03 [Marketing Authorisation Holder] Warner Chilcott UK Ltd. [Revision] 6 [Date of issue of Market Authorisation valid throughout the European Union] 28/07/2006 [Pharmaco-therapeutic Group]Sex hormones and modulators of the genital system [Therapeutic Indication] Intrinsa is indicated for the treatment of hypoactive sexual desire disorder (HSDD) in bilaterally oophorectomised and hysterectomised (surgically induced menopause) women receiving concomitant estrogen therapy. ★Livensa(testosterone) Sexual Dysfunctions, Psychological - 28/07/2006 Authorised 1. Summary for the public 2. All Authorised Presentations 3. Scientific Discussion 4. Procedural steps taken before authorisation 5. Procedural steps taken and scientific information after authorisation Product Information, please see below Annex I - Summary of product Characteristics Annex IIA - Manufacturing Authorisation Holder responsible for Batch Release Annex IIB - Conditions of the Marketing Authorisation Annex IIIA - Labelling Annex IIIB - Package Leaflet [Name] Livensa Livensa 300 micrograms/24 hours transdermal patch Each patch of 28 cm2 contains 8.4 mg testosterone and provides 300 micrograms of testosterone per 24 hours. [EMEA Product number] EMEA/H/C/000630 [Active substance] testosterone [INN or common name] testosterone [Therapeutic area] Sexual Dysfunctions, Psychological [ATC Code] G03BA03 [Marketing Authorisation Holder] Warner Chilcott Deutschland GmbH [Revision] 6 [Date of issue of Market Authorisation valid throughout the European Union] 28/07/2006 [Pharmaco-therapeutic Group] Sex hormones and modulators of the genital system [Therapeutic Indication] Livensa is indicated for the treatment of hypoactive sexual desire disorder (HSDD) in bilaterally oophorectomised and hysterectomised (surgically induced menopause) women receiving concomitant estrogen therapy. ●CHMP Press Releases ●CHMP: Committee meeting reports諮問委員会審議品目一覧 - Summaries of Opinion ---Substance/INN Trade Name Pharmaceuticalform Strength OpinionAdoption Date ●[EU Referrals] human medicinal products[医薬品のReferralリスト]Refferal=紹介の意だが、国別審査方式による製品リスト
[1362]●製品 テストステロンゲルtestosterone Gel(Fortesta - Endo)
日本語版註）テストステロンゲルtestosterone Gel(Fortesta - Endo)
【別名】 【開発元】Endo Pharmaceuticals [DBR_ID]
【化学名】17-beta hydroxyandrost-4-en-3-one
【承認】FDA申請=31-May-2002、FDA承認=29-Dec-2010、米国発売3-Mar-2011 ; 【製剤】FORTESTA (testosterone) Gel is supplied as a metered-dose pump. One pump actuation delivers 10 mg of testosterone. each container is capable of dispensing 120 pump actuations. One pump actuation dispenses 0.5 g of gel. 【適応】indicated for replacement therapy in males for conditions associated with a deficiency or absence of endogenous testosterone: 1)(原発性性腺機能低下症) Primary hypogonadism (congenital or acquired) 2)(低ゴナドトロピン性性機能不全) Hypogonadotrophic hypogonadism (congenital or acquired) 【用法用量】初回１日１回朝 testosterone 40mg(4 pump actuations)を塗布。 70mg迄増量可。
【作用】Endogenous androgens, including testosterone and dihydrotestosterone (DHT), are responsible for the normal growth and development of the male sex organs and for the maintenance of secondary sex characteristics. These effects include the growth and maturation of the prostate, seminal vesicles, penis and scrotum; the development of male hair distribution, such as facial, pubic, chest and axillary hair; laryngeal enlargement, vocal cord thickening, alterations in body musculature and fat distribution. Testosterone and DHT are necessary for the normal development of secondary sex characteristics. Male hypogonadism results from insufficient production of testosterone and is characterized by low serum testosterone concentrations. Symptoms associated with male hypogonadism include erectile dysfunction and decreased sexual desire, fatigue and loss of energy, mood depression, regression of secondary sexual characteristics, and osteoporosis.Male hypogonadism can present as primary hypogonadism caused by defects of the gonads, such as Klinefelter’s Syndrome or Leydig cell aplasia while secondary hypogonadism is the failure of the hypothalamus or pituitary to produce sufficient gonadotropins (FSH, LH). 【特徴】
【製品情報】www.fortestagel.com 【添付文書】FORTESTA-PI
【提携】 【EU】
【日本】未開発 【その他】
The FDA has approved Fortesta (Endo), a topical gel, for testosterone replacement therapy in adult males with hypogonadism. It is classified as a Schedule III controlled substance. Table 1 lists some available testosterone products, including 2 other gels.
【日本語版コメント1362〜性腺機能低下に対する新規テストステロンゲル(Fortesta - Endo)】
日本では性腺機能低下症は、極めて稀な疾患で薬剤需要が少ないため、外用テストステロン製剤は一般用のグローミン軟膏[大東製薬工業]のみ。 米国では医療用としてテストステロン埋め込みペレットTESTOPEL[SLATE PHARMS]、持続性バッカル製剤STRIANT[ACTIENT PHARMS]、外用液AXIRON[ELI LILLY]、経皮フイルムANDRODERM[WATSON]、経皮ゲルANDROGEL[ABBOTT]およびTESTIM[AUXILIUM PHARMS]と実に多彩だ。→詳細は参考資料●MLリソース：Androgen/男性ホルモンに纏めた。＜日本語版コメント要約＞
・性腺機能低下の成人男性におけるテストステロン補充療法薬として、局所用ゲルFortestaが承認された。
・本剤は性腺機能が低下した男性のテストステロン濃度を正常範囲まで上昇させる。
・臨床試験の投与期間は90日で、長期安全性は不明。
●承認データ：FDA ●FDA Newsroom - FDA Press Releases ●Index to Drug-Specific Information ●2004.5.1 以降 Drugs@FDA
★Drug Name(s) =FORTESTA (TESTOSTERONE) FDA Application No. =(NDA) 021463 Active Ingredient(s)=TESTOSTERONE Company =Endo Pharmaceuticals, Inc. Dosage Form/Route =GEL, METERED; TRANSDERMAL Strength =10MG/0.5GM ACTIVATION - Approval Date=12/29/2010[000][Approval]:Label[添付文書]|Letter[承認書]| 申請May 31, 2002 適応for replacement therapy in males for conditions associated with a deficiency or absence of endogenous testosterone. Original Approval or Tentative Approval Date:December 29, 2010 Chemical Type: 3 New formulation Review Classification: S Standard review drug
●Electronic Orange Book /2011.8.15/
Application Number: N021463 Active Ingredient : TESTOSTERONE Proprietary Name : FORTESTA [ENDO PHARMS] GEL, METERED; TRANSDERMAL 10MG/0.5GM ACTIVATION Approval Date : Dec 29, 2010 Exclusivity Data : NP Dec 29, 2013 Patent Data : 6319913 Nov 9, 2018 U - 490 6579865 Nov 9, 2018 Y Application Number: N021454 Active Ingredient : TESTOSTERONE Proprietary Name : TESTIM [AUXILIUM PHARMS] GEL; TRANSDERMAL 1% (5GM/PACKET) Approval Date : Oct 31, 2002 Exclusivity Data : - Patent Data : 7320968 Jan 18, 2025 U - 843 7608605 Apr 21, 2023 U - 1009 7608606 Apr 21, 2023 U - 1009 7608607 Apr 21, 2023 U - 1009 7608608 Apr 21, 2023 U - 1009 7608609 Apr 21, 2023 U - 1009 7608610 Apr 21, 2023 U - 1009 7935690 Apr 21, 2023 U - 1009 Application Number: N021015 Active Ingredient : TESTOSTERONE Proprietary Name : ANDROGEL [ABBOTT PRODS] GEL, METERED; TRANSDERMAL 1% (1.25GM,2.5GM,5GM/ACTIVATION) Approval Date : Feb 28, 2000[2.5g,5g]Sep 26, 2003[1.25g] Exclusivity Data : 6503894 Aug 30, 2020 U - 490 6503894*PED Mar 1, 2021 Patent Data : - Application Number: N022309 Active Ingredient : TESTOSTERONE Proprietary Name : ANDROGEL [ABBOTT PRODS] GEL, METERED; TRANSDERMAL 1.62% (20.25MG/1.25GM ACTIVATION) Approval Date : Apr 29, 2011 Exclusivity Data : NP Apr 29, 2014 Patent Data : 6503894 Aug 30, 2020 U - 1103 Application Number: N020489 Active Ingredient : TESTOSTERONE Proprietary Name : ANDRODERM [WATSON LABS] FILM, EXTENDED RELEASE; TRANSDERMAL 2.5MG/24HR; 5MG/24HR Approval Date : Sep 29, 1995[2.5mg]May 2, 1997[5mg] Exclusivity Data : x Patent Data : 5152997 Dec 11, 2010 U - 490 5164190 Dec 11, 2010
Appl
NoTE Code RLD Active
IngredientDosage Form;
RouteStrength Proprietary
NameApplicant 承認日 特許 先発権 A083976 Yes METHYLTESTOSTERONE CAPSULE; ORAL 10MG TESTRED VALEANT PHARM INTL Jan 1, 1982前 x x A080767 BP No METHYLTESTOSTERONE TABLET; ORAL 10MG METHYLTESTOSTERONE IMPAX LABS Jan 1, 1982前 x x A084310 BP No METHYLTESTOSTERONE TABLET; ORAL 25MG METHYLTESTOSTERONE IMPAX LABS Jan 1, 1982前 x x A086450 BP No METHYLTESTOSTERONE TABLET; ORAL 10MG ANDROID 10 VALEANT PHARM INTL Jan 1, 1982前 x x A087147 BP Yes METHYLTESTOSTERONE TABLET; ORAL 25MG ANDROID 25 VALEANT PHARM INTL Jan 1, 1982前 x x N020489 Yes TESTOSTERONE FILM, EXTENDED RELEASE; TRANSDERMAL 2.5MG/24HR; 5MG/24HR ANDRODERM WATSON LABS Sep 29, 1995[2.5mg]
May 2, 1997[5mg]2010 x N021015 Yes TESTOSTERONE GEL, METERED; TRANSDERMAL 1% (1.25GM,2.5GM,5GM/ACTIVATION) ANDROGEL ABBOTT PRODS Feb 28, 2000[2.5g,5g]
Sep 26, 2003[1.25g]2021 x N022309 Yes TESTOSTERONE GEL, METERED; TRANSDERMAL 1.62% (20.25MG/1.25GM ACTIVATION) ANDROGEL ABBOTT PRODS Apr 29, 2011 2020 2014 N021463 Yes TESTOSTERONE GEL, METERED; TRANSDERMAL 10MG/0.5GM ACTIVATION FORTESTA ENDO PHARMS Dec 29, 2010 2018 2013 N021454 BX Yes TESTOSTERONE GEL; TRANSDERMAL 1% (5GM/PACKET) TESTIM AUXILIUM PHARMS Oct 31, 2002 2023 x A080911 Yes TESTOSTERONE PELLET; IMPLANTATION 75MG TESTOPEL SLATE PHARMS Jan 1, 1982前 x x N022504 Yes TESTOSTERONE SOLUTION, METERED; TRANSDERMAL 30MG/1.5ML ACTIVATION AXIRON ELI LILLY AND CO Nov 23, 2010 2017 2013 N021543 Yes TESTOSTERONE TABLET, EXTENDED RELEASE; BUCCAL 30MG STRIANT ACTIENT PHARMS Jun 19, 2003 2019 x A090387 AO No TESTOSTERONE CYPIONATE INJECTABLE; INJECTION 100MG,200MG/ML TESTOSTERONE CYPIONATE BEDFORD Jul 15, 2010 x x A040530 AO No TESTOSTERONE CYPIONATE INJECTABLE; INJECTION 200MG/ML TESTOSTERONE CYPIONATE PADDOCK Jan 31, 2005 x x A085635 AO Yes TESTOSTERONE CYPIONATE INJECTABLE; INJECTION 100MG,200MG/ML DEPO-TESTOSTERONE PHARMACIA AND UPJOHN Jan 1, 1982前 x x A040615 AO No TESTOSTERONE CYPIONATE INJECTABLE; INJECTION 100MG,200mg/ML TESTOSTERONE CYPIONATE SANDOZ Aug 10, 2006 x x A040652 AO No TESTOSTERONE CYPIONATE INJECTABLE; INJECTION 200MG/ML TESTOSTERONE CYPIONATE SYNERX PHARMA Dec 11, 2006 x x A086030 AO No TESTOSTERONE CYPIONATE INJECTABLE; INJECTION 200MG/ML TESTOSTERONE CYPIONATE WATSON LABS Jan 1, 1982前 x x N009165 AO Yes TESTOSTERONE ENANTHATE INJECTABLE; INJECTION 200MG/ML DELATESTRYL ENDO PHARM Jan 1, 1982前 x x A040575 AO No TESTOSTERONE ENANTHATE INJECTABLE; INJECTION 200MG/ML TESTOSTERONE ENANTHATE PADDOCK Jun 14, 2006 x x A040647 AO No TESTOSTERONE ENANTHATE INJECTABLE; INJECTION 200MG/ML TESTOSTERONE ENANTHATE SYNERX PHARMA Oct 5, 2009 x x A085598 AO No TESTOSTERONE ENANTHATE INJECTABLE; INJECTION 200MG/ML TESTOSTERONE ENANTHATE WATSON LABS Jan 1, 1982前 x x
●EU承認 ●ema - Human Medcines ●List of Authorized Products (EPARs)★[A-Z 承認品目] 該当なし
●
[1208]
[1208]●製品 Dehydroepiandrosterone[DHEA]
日本語版註）Dehydroepiandrosterone[DHEA]
【別名】プラステロン硫酸ナトリウム (Sodium Prasterone Sulfate) 【開発元】 [DBR_ID]
【化学名】Monosodium 17-oxoandrost-5-en-3β-yl sulfate dihydrate ; CAS REGISTRY NO.:53-43-0
【承認】FDA申請=、FDA承認= ; 【製剤】 【適応】 【用法用量】 【作用】 【特徴】 【製品情報】 【添付文書】 【提携】 【EU】 【日本】マイリス注(100mg)[]薬価収載1981.9、発売1981.2;マイリス注(200mg)[]薬価収載1984.6、発売1984.8; 【製剤〜日本】1バイアル中 プラステロン硫酸ナトリウム (日局) 無水物として100mg,200mgを含有 【適応〜日本】妊娠末期子宮頸管熟化不全 (子宮口開大不全、頸部展退不全、頸部軟化不全)における熟化の促進 【用法用量〜日本】通常、プラステロン硫酸ナトリウム (無水物)として100〜200mgを注射用水又は5w/v％ブドウ糖注射液で100mg／10mLの濃度となるように用時溶解し、妊娠末期の妊婦に1日1回、週2〜3回静脈内投与する。 【添付文書〜日本】 【その他】子宮頸管熟化剤 (DHA-S製剤)
マイリス注(100mg)／マイリス注(200mg) [製造販売元／日本オルガノン株式会社] マイリス膣坐剤[製造販売元／日本オルガノン株式会社]
【日本語版コメント】
日本でも老化防止・若返りなどアンチエイジング薬としてDHEA錠剤あるいはDHEA含有化粧品クリームとして販売されている。 多くは輸入品の健康サプリ。
DHEAは体内でつくられるが、２５才をピークに老化と共に分泌量が減少していく。 曰く、「DHEAを補給すると，気分がよくなり，エネルギーや性欲を増進させ，ストレスホルモンに対抗し，筋肉を引き締め，免疫系を強め，ガンや心臓病を予防。」 いわゆるHRTなので確かに理にかなっているわけだが、特に安全性を中心にこれを検証する。→詳細は参考資料●MLリソース：Androgen/男性ホルモンに纏めた。＜日本語版コメント要約＞
・内因性副腎ステロイドのデヒドロエピアンドロステロン（DHEA）は、加齢に伴う筋肉、記憶力、および性機能の低下を回復するサプリメントとして、米国で広く宣伝されている。
・DHEAは副腎機能不全や全身性エリテマトーデス患者の症状を改善すると思われる。
・高齢者の認知機能改善や若年男性の運動能力改善あるいは筋肉量増加作用については、十分な証拠がない。
・高齢者において骨吸収低下や体脂肪低下、インスリン感受性改善などの報告があるが、いずれについても大規模臨床試験が必要である。
●承認データ：FDA
●関連資料
[三菱化学BCL]デハイドロエピアンドロステロンサルフェート(DHEA-S) - 男性ホルモンの中間代謝産物。DHEAの硫化物で、より血中半減期が長い。Cushing症候 群の病型判定や男性化徴候の指標。 日本抗加齢医学会 -Japanese Society of Anti-Aging Medicine - 抗加齢医学〜全文公開 皮膚のrejuvenation：ホルモン補充療法 - by 吉村浩太郎 3. Adrenopause DHEA（dehydroepiandrosterone）はコレステロールから主に副腎で合成されるホルモン 前駆物質で、やはり年齢とともに減少することが知られている。テストステロンをはじめ とする性ホルモン全般の原料となり、血中濃度は平均して女性よりも男性で高い。日内変 動があるためDHEA-S（dehydroepiandrosterone sulfate）の血中濃度が測定されることが 多い。海外では医薬品ではなく１錠25mg程度のサプリメントとして販売されており1日25- 100mg程度投与される。副作用は極めて少ないが、過剰投与は避ける。 [北里大学薬学部]問題の多い健康食品10種類のデータベース（一般向け）「DHEA(ディーエッチイーエー)」 DHEA文献集
[1164]●製品testosterone buccal system (Striant [Columbia Labs.,Inc.])
【日本語版コメント】
勃起不全治療剤は、性欲増進作用も男性機能を復活させるわけではない。 女性の更年期障害・骨粗鬆症にホルモン補充療法[HRT]が一般的であるように(昨2002年7月のWHI報告による乳癌リスクで事情はかなり変わったが)、米国では男性更年期障害として男性機能減弱を捉え、テストステロンの補充療法が広く支持されるようになってきた。 性ホルモン欠乏により更年期障害・骨粗鬆症だけではなく、痴呆症、動脈硬化への効果にも言及され"究極の若返り薬"という信仰がある。 米国ではテストステロン欠乏症男性が800万人でうち60万人が治療を受けているとのこと。
その動きを加速するように、最近新たな外用テストステロン製剤がFDA承認された。 そのメーカーAuxilium社によると、testosterone replacement therapy市場が2008年に20億ドル見込み。米国でhypogonadism男性は推定4-500万人。うちtestosterone療法を受けているのは20%。 臨床試験は米欧74施設hypogonadism患者690人で実施、90日後の結果で、性的能力は59%増、勃起能力78%増、筋肉量3.5 pounds平均増、骨密度も改善。
日本では、医療面・新薬開発面でもその動きはない。→詳細は参考資料●リソース：Androgen/男性ホルモンに纏めた。＜日本語版コメント用要約＞ ・2つの新しい局所用テストステロン製剤の1%ゲル（Testim）とバッカル錠（Striant）が男性の性機能低下症の治療薬としてFDAに承認された
・副作用。 経口剤では肝炎・肝臓がん等肝障害のリスクがあるが、外用剤での可能性は低い。 しかし前立腺肥大、睡眠時無呼吸の増加の報告などがある。
・ゲル剤は1日1回肩か上腕部に塗布することにより、血清テストステロン濃度を正常範囲まで増加することができる。 ゲル剤は接触により移行するため、女性パートナーのテストステロン濃度の増加が問題となる。
・バッカル錠は1錠を1日2回歯肉に付着させるが、12時間同じ場所に付着させておく必要がある。
日本語版註）testosterone buccal system (Striant [Columbia Labs.,Inc.])
【別名】 【開発元】Columbia Labs.,Inc. [DBR_ID]
【化学名】
【承認】FDA申請=、FDA承認=19-Jun-2003、発売=Jul-2003 ;【製剤】Striant(TM) (testosterone buccal system) is designed to adhere to the gum or inner cheek. It provides a controlled and sustained release of testosterone through the buccal mucosa as the buccal system gradually hydrates. Insertion of Striant(TM) twice a day, in the morning and in the evening, provides continuous systemic delivery of testosterone. Striant(TM) is a white to off-white colored, monoconvex, tablet-like, mucoadhesive buccal system. Striant(TM) adheres to the gum tissue above the incisors, with the flat surface facing the cheek mucosa. 【適応】Striant(TM) is indicated for replacement therapy in males for conditions associated with a deficiency or absence of endogenous testosterone:[テストステロン欠乏に伴う症状の男性への補充療法]
Primary hypogonadism 原発性性機能低下症(congenital or acquired) − testicular failure due to cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchidectomy, Klinefelter's syndrome, chemotherapy, or toxic damage from alcohol or heavy metals. These men usually have low serum testosterone levels and gonadotropins (FSH, LH) above the normal range.
Hypogonadotropic hypogonadism 低ゴナドトロピン性性機能低下症(congenital or acquired) − idiopathic gonadotropin or LHRH deficiency, or pituitary hypothalamic injury from tumors, trauma, or radiation. These patients have low serum testosterone levels but have gonadotropins in the normal or low range. 【製品情報】http://www.columbialabs.com/Striantdisclamer.htm 【添付文書】http://www.columbialabs.com/Striant%20Package%20Insert.pdf 【EU】 【日本】未開発 【その他】Manufactured by: Mipharm S.p.A. Milan, Italy
●承認データ：FDA
情報ソース●CDER New and Generic Drug Approvals: 1998-2003 Striant (testosterone buccal system) mucoadhesive, Columbia Laboratories, Inc. Application #=NDA 21-543 Approval Date=6/19/03 Letter Posted=7/8/03 Label Posted =7/8/03 Review Posted=
●Electronic Orange Book Application Number: 021543 Active Ingredient : TESTOSTERONE Proprietary Name : STRIANT (Tablet, Extended Release; Buccal 30MG ) Approval Date : JUN 19, 2003 Exclusivity Data : JUN 19,2006 Patent Data : 4615697 OCT 07,2003 6248358 AUG 23,2019
●Columbia Labs Inc.
- 同社はホルモン剤外用剤専門メーカー 【製品情報】http://www.columbialabs.com/Striantdisclamer.htm 【添付文書】http://www.columbialabs.com/Striant%20Package%20Insert.pdf ●Investor > 06/20/03 U.S. FDA APPROVES STRIANT(TM), A NEW TREATMENT FORM FOR MEN WITH A DEFICIENCY
OR ABSENCE OF TESTOSTERONE > 06/20/03 CONFERENCE CALL REGARDING FDA APPROVAL OF STRIANT(TM) (TESTOSTERONE BUCCAL SYSTEM) > 06/09/03 MARKETING PARTNERSHIP WITH MIPHARM S.p.A. FOR STRIANT(TM) (TESTOSTERONE BUCCAL
SYSTEM) MUCOADHESIVE IN ITALY > 12/03/02 Submission of Marketing Authorization Application to U.K. Medicines Control
Agency for Striant(TM)
[1164]●製品testosterone gel(Testim [Auxilium Pharma])
日本語版註）testosterone gel(Testim [Auxilium Pharma])
【別名】AA2500 【開発元】Auxilium Pharma(製剤技術はBentley Pharmaceuticals, Inc.から) [DBR_ID]
【化学名】
【承認】FDA申請=Dec-2001(FDA受付6-Mar-2002)、FDA承認=31-Oct-2002、発売=4-Feb-2003 ;【製剤】Testim(TM) (testosterone gel) is a clear to translucent hydroalcoholic topical gel containing 1% testosterone. Testim(TM) provides continuous transdermal delivery of testosterone for 24 hours, following a single application to intact, clean, dry skin of the shoulders and upper arms. 【適応】Testim is indicated for testosterone replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone[テストステロン欠乏に伴う症状の成人男性への補充療法] 【製品情報】 【添付文書】http://www.auxilium.com/targets_020403.html 【EU】申請=2002.4 【日本】未開発 【その他】Androgelより吸収率が30%上回る
●承認データ：FDA
情報ソース●CDER New and Generic Drug Approvals: 1998-2003 Testim 1% (testosterone gel), 50 mg and 100 mg Auxilium Pharmaceuticals, Inc. Application #=NDA 21-454 Approval Date=10/31/02 Letter Posted=11/18/02 Label Posted =10/31/02 Review Posted=
●Electronic Orange Book Application Number: 021454 Active Ingredient : TESTOSTERONE Proprietary Name : TESTIM (Gel; Topical 1% ) Approval Date : OCT 31, 2002 Exclusivity Data : OCT 31,2005 Patent Data : 5023252 JUN 11,2008
●Auxilium Pharmaceuticals, Inc
- http://www.auxilium.com/ Testim(TM) Full Prescribing Information ●News & LinksSeptember 22, 2003
STUDY SHOWS AUXILIUM'S TESTIM(R) TESTOSTERONE GEL IMPROVES BONE MINERAL DENSITY AND BODY COMPOSITION IN AGING MEN WITH HYPOGONADISMJune26, 2003
AUXILIUM RECEIVES REGULATORY APPROVAL TO MARKET TESTIM™ TESTOSTERONE GEL IN THE UNITED KINGDOM
June21, 2003
RESPONSE TO TESTOSTERONE SUPPLEMENTATION WITH A NEW TOPICAL TESTOSTERONE GEL (TESTIM™) IN OLDER MEN WITH DIABETES MELLITUS
June 9, 2003
AUXILIUM PHARMACEUTICALS ANNOUNCES RESULTS OF LANDMARK STUDY SHOWING TESTIM™ TESTOSTERONE GEL INCREASES INTEREST IN SEX AND IMPROVES SEXUAL PERFORMANCE IN MALES WITH HYPOGONADISM
April 29, 2003
AUXILIUM’S NEW TESTIM™ GEL SHOWN TO NORMALIZE TESTOSTERONE LEVELS AND IMPROVE SEXUAL FUNCTION, BODY COMPOSITION AND MOOD IN AGING MALES
April 23, 2003
AUXILIUM’S NEW TESTIM™ GEL SHOWN TO HAVE 30 PERCENT GREATER TESTOSTERONE ABSORPTION IN HYPOGONADAL MEN THAN ANDROGEL®
March 14, 2003
STUDY SHOWS PATIENTS TREATED WITH NEW TESTOSTERONE GEL SHOW IMPROVEMENTS IN SEXUAL FUNCTION, MOOD AND OTHER AREAS
February 4, 2003
AUXILIUM LAUNCHES TESTIM™ GEL FOR TREATMENT OF TESTOSTERONE DEFICIENCY IN MEN - 2003.2.4発売。testosterone replacement therapy市場が2008年に20億ドル見込み。米国でhypogonadism男性は推定4-500万人。うちtestosterone療法を受けているのは20%。 臨床試験は米欧74施設hypogonadism患者690人で実施、90日後の結果で、性的能力は59%増、勃起能力78%増、筋肉量3.5 pounds平均増、骨密度も改善。
November 1, 2002
AUXILIUM RECEIVES U.S. FDA APPROVAL TO MARKET TESTIM™ TESTOSTERONE REPLACEMENT GEL
March 6, 2002
AUXILIUM NEW DRUG APPLICATION FOR TESTOSTERONE GEL ACCEPTED FOR REVIEW BY FDA
[1080]●製品 testosterone gel (Androgel [Unimed])
日本語版註）●製品 testosterone gel (Androgel [Unimed])
【別名】 【開発元】Unimed [DBR_ID]46073
【化学名】
【承認】FDA申請=、FDA承認=28-FEB-00、発売=2000.6.14(2001.5.30 TAPと共同販売) ;【製剤】 【適応】For replacement therapy in males for conditions associated with a deficiency or absence of endogenous testosterone 【製品情報】●FDA Approves AndroGel(TM), First Gel to Treat Male Testosterone Deficiency(February 29, 2000) 【添付文書】2/29/00 |View full prescribing information. 【EU】 【日本】未開発 【その他】Unimed社はSolvayの子会社[1999.7買収]。
------------------------------------ 46073=TESTODERM,TESTOSTERONE-TTS 《UK》ANDROPATCH（SMITHKLINE BEECHAM）08-96＊ ANDRODERM[;THERATECH-US];ANDROPATCH;TESTODERM;TESTOSTERONE-TRANSDERMAL;TESTOSTERONE-TTS;TRANSDERMAL TESTOSTERONE ALZA CORP[US]/STADAPHARM GMBH ------------------------------------
【日本語版コメント】
米国初testosteroneゲル製剤。 低テストステロン症は、性腺機能低下症[hypogonadism]として知られ、米国では400-500万人。
Androgel はUnimed社によれば「疼痛を伴う筋注や刺激性の強いパッチ製剤に対して、簡便で、効果のある代替療法となる」[●FDA Approves AndroGel(TM), First Gel to Treat Male Testosterone Deficiency(February 29, 2000)]
米国では、男性機能回復や筋力増強といった目的で需要が多いらしいが、日本ではバイアグラが低調である理由と同一と思うが、テストステロン外用製剤は開発されていない。
●承認データ：FDA
情報ソース●Drug Approvals for February 2000 Original Application #: 021015 Approval Date: 28-FEB-00 Trade Name: ANDROGEL Chemical Type: 3 Therapeutic Potential: S Dosage Form: GEL Applicant: UNIMED PHARMACEUTICALS INC Active Ingredient(s): TESTOSTERONE OTC/RX Status: RX Indication(s): For replacement therapy in males for conditions associated with a deficiency or absence of endogenous testosterone
情報ソース●CDER New and Generic Drug Approvals: 1998-2003 AndroGel (testosterone gel). , Rx Unimed Pharmaceuticals, Inc Application #=NDA 21-015 Approval Date=2/28/00 Letter Posted=2/29/00 Label Posted =2/29/00 Review Posted= AndroGel Indication: AndroGel is indicated for replacement therapy in males for conditions associated with a deficiency or absence of endogenous testosterone AndroGel (testosterone gel), Rx Unimed Pharmaceuticals, Inc. Application #=NDA 21-015/S4 Approval Date=10/22/02 Letter Posted=10/28/02 Label Posted =10/25/02 Review Posted=
●Electronic Orange Book Application Number: 021015 Active Ingredient : TESTOSTERONE Proprietary Name : ANDROGEL (Gel; Topical 1% ) Approval Date : FEB 28, 2000 Exclusivity Data : FEB 28,2003 Patent Data : 6503894 AUG 30,2020
●List of Orphan Designations and Approvals
Generic Name: Dihydrotestosterone Trade Name: Androgel -DHT Orphan Indication: Treatment of weight loss in AIDS patients with HIV-associated wasting. Sponsor: Unimed Pharmaceuticals, Inc. Address: Buffalo Grove, IL Contact: Mr. Donald Peckels Phone: (847) 541-2525 Fax: (847) 541-2569 Designation Date: 02/05/1996 -------------------------------------------------------------------------------- Generic Name: Testosterone Trade Name: Androgel Orphan Indication: Treatment of weight loss in AIDS patients with HIV-associated wasting. Sponsor: Unimed Pharmaceuticals, Inc. Address: Buffalo Grove, IL Contact: Mr. Donald Peckels Phone: (847) 541-2525 Fax: (847) 541-2569 Designation Date: 02/05/1996 -------------------------------------------------------------------------------- Generic Name: Testosterone Trade Name: TheraDerm Testosterone Transdermal System Orphan Indication: For use as physiologic testosterone replacement in androgen deficient HIV+ patients with an associated weight loss. Sponsor: Watson Laboratories Address: Salt Lake City, UT Contact: Ms. Dorothy Frank Phone: (801) 588-6200 Fax: (801) 583-8135 Designation Date: 09/22/1997 -------------------------------------------------------------------------------- Generic Name: Testosterone propionate ointment 2% Trade Name: Orphan Indication: Treatment of vulvar dystrophies. Sponsor: Star Pharmaceuticals, Inc. Address: Pompano Beach, FL Contact: Mr. Scott Davidson Phone: (954) 971-9704 Fax: Designation Date: 07/31/1991 -------------------------------------------------------------------------------- Generic Name: Testosterone sublingual Trade Name: Orphan Indication: Treatment of constitutional delay of growth and puberty in boys. Sponsor: Bio-Technology General Corp. Address: Iselin, NJ Contact: Mr. Briti Kundu Phone: (732) 632-8800 Fax: (732) 632-8844 Designation Date: 01/16/1991
■Unimed Pharmaceuticals Products
Marketed Products AndroGel™ Anadrol®-50 Teveten® Investigational Products Andractim™ Compassia™ ReLibra™ =======================================================
■AndroGel 低テストステロン症は、性腺機能低下症[hypogonadism]として知られ、米国では400-500万人。
AndroGel™ is the first-ever testosterone replacement gel to be approved by the FDA for replacement therapy in men for conditions associated with low testosterone. Low testosterone, also known as hypogonadism, affects approximately four to five million American men. The condition is linked with diminished interest in sex, impotence, reduced lean body mass, decreased bone density and lowered mood and energy levels. AndroGel™ will be available with a prescription in pharmacies throughout the United States by mid-summer.
View full prescribing information.
●Press Release
Unimed Pharmaceuticals, Inc. Receives Patent on AndroGel(R) (01/09/2003) Unimed Pharmaceuticals, Inc. Announces Management Change (08/30/2001) Unimed and TAP Join Forces to Co-Promote AndroGel® (05/30/2001) Unimed Pharmaceuticals, Inc. to be Sole Marketer of Marinol® (01/02/2001) New Testosterone Replacement Gel, AndroGel®, Available Nationwide to Treat Men with Low Testosterone (06/14/2000) FDA Approves AndroGel™, First Gel to Treat Male Testosterone Deficiency (02/29/2000)
●FDA Approves AndroGel(TM), First Gel to Treat Male Testosterone Deficiency Androgel はUnimed社によれば「疼痛を伴う筋注や刺激性の強いパッチ製剤に対して、簡便で、効果のある代替療法となる」
BUFFALO GROVE, Ill. (February 29, 2000) -- Unimed Pharmaceuticals, Inc. today announced that AndroGel(TM) 1% (testosterone gel) (C-III) was approved by the U.S. Food and Drug Administration (FDA). The approval makes AndroGel(TM) the first-ever testosterone replacement gel to be approved by the FDA for replacement therapy in men for conditions associated with low testosterone. Low testosterone, also known as hypogonadism, affects approximately four to five million American men. The condition is linked with diminished interest in sex, impotence, reduced lean body mass, decreased bone density and lowered mood and energy levels. AndroGel(TM) will be available with a prescription in pharmacies throughout the United States by mid-summer. Unimed Pharmaceuticals, Inc. is a wholly owned subsidiary of Solvay Pharmaceuticals, Inc.
"We believe that doctors and men who are waiting for a more convenient testosterone treatment will regard AndroGel(TM) as a very attractive alternative to existing testosterone replacement therapy." said Robert E. Dudley, president and CEO, Unimed Pharmaceuticals, Inc. "AndroGel(TM) provides an easy, effective, invisible alternative to painful deep muscle injections and potentially irritating patches."
AndroGel(TM) is a unique, clear, colorless topical gel that men apply once daily to the shoulders, upper arms and/or abdomen. Upon application, AndroGel(TM) dries within a few minutes, during which time the skin absorbs the testosterone. The skin serves as a reservoir for the hormone, which slowly enters the bloodstream. Normal testosterone levels are restored soon after application. AndroGel(TM) is the only FDA approved testosterone replacement therapy available in gel form. AndroGel(TM) provides men with a safe, effective and easy-to-use treatment that can be applied at home.
Clinical data from a U.S. phase III study conducted in men with hypogonadism indicated that AndroGel(TM) quickly raised circulating testosterone to desirable levels, and maintained it within normal range. The study also found that AndroGel(TM) increased sex drive, bone mineral density, and lean body mass and improved mood and energy levels.
"Research supporting the use of AndroGel(TM) is extremely solid and the unique gel delivery method is very versatile," said Ronald S. Swerdloff, M.D., Chief and Professor of Medicine, Division of Endocrinology at Harbor-UCLA Medical Center. "Testosterone deficient men who use AndroGel(TM) can experience physical and psychological benefits with this convenient, well-tolerated gel."
Safety data from clinical studies of AndroGel(TM) demonstrate it to be well tolerated. Androgens are contraindicated in men with carcinoma of the breast, or known or suspected carcinoma of the prostate. Geriatric patients treated with androgens may be at an increased risk for the development of prostatic hyperplasia and prostatic carcinoma. AndroGel(TM) is not indicated for use in women and has not been evaluated in women. Pregnant women should avoid skin contact with AndroGel(TM) application sites in men. Testosterone may cause fetal harm.
Studies have shown that during vigorous skin to skin contact some of the testosterone in AndroGel(TM) can be transferred to the untreated individual. Residual testosterone on the skin can be removed with soap and water. Testosterone should not be used to improve athletic performance.
For full prescribing information, physicians and patients may visit www.Unimed.com or call 1-877-463-7645.
Unimed Pharmaceuticals, Inc., a wholly owned subsidiary of Solvay Pharmaceuticals, Inc., focuses on drugs with multiple indications in the therapeutic areas of hypertension, endocrinology, urology, HIV and other infectious diseases.
Unimed currently markets TevetenR (eprosartan mesylate) for the treatment of hypertension, Marinol (dronabinol) as an appetite stimulant for people living with HIV disease and as an antiemetic for people with cancer, AnadrolR-50 (oxymetholone) for the treatment of various anemias, and MaxaquinR (lomefloxacin HCl), a broad-spectrum quinolone antibiotic, for both complicated and uncomplicated urinary tract infections.
Solvay Pharmaceuticals, Inc. of Marietta, Georgia, is a research-based pharmaceuticals company, active in the therapeutic areas of cardiology, gastroenterology, mental health and women's health. It is a member of the worldwide Solvay Group of chemical and pharmaceutical companies, headquartered in Brussels, Belgium.
●FDA Approves AndroGelO, First Gel to Treat Male Testosterone Deficiency
For more information contact: Marissa Weber Edelman Worldwide (312) 240-2841 marissa_weber@edelman.com -- or -- Shelly Wilt Edelman Worldwide (312)240-2839 shelly_wilt@edelman.comBUFFALO GROVE, Ill. (February 29, 2000)
Unimed Pharmaceuticals, Inc. today announced that AndroGelO 1% (testosterone gel) (C-III) was approved by the U.S. Food and Drug Administration (FDA). The approval makes AndroGelO the first-ever testosterone replacement gel to be approved by the FDA for replacement therapy in men for conditions associated with low testosterone. Low testosterone, also known as hypogonadism, affects approximately four to five million American men. The condition is linked with diminished interest in sex, impotence, reduced lean body mass, decreased bone density and lowered mood and energy levels. AndroGelO will be available with a prescription in pharmacies throughout the United States by mid-summer. Unimed Pharmaceuticals, Inc. is a wholly owned subsidiary of Solvay Pharmaceuticals, Inc.
“We believe that doctors and men who are waiting for a more convenient testosterone treatment will regard AndroGelO as a very attractive alternative to existing testosterone replacement therapy.” said Robert E. Dudley, president and CEO, Unimed Pharmaceuticals, Inc. “AndroGelO provides an easy, effective, invisible alternative to painful deep muscle injections and potentially irritating patches.”
AndroGelO is a unique, clear, colorless topical gel that men apply once daily to the shoulders, upper arms and/or abdomen. Upon application, AndroGelO dries within a few minutes, during which time the skin absorbs the testosterone. The skin serves as a reservoir for the hormone, which slowly enters the bloodstream. Normal testosterone levels are restored soon after application. AndroGelO is the only FDA approved testosterone replacement therapy available in gel form. AndroGelO provides men with a safe, effective and easy-to-use treatment that can be applied at home.
Clinical data from a U.S. phase III study conducted in men with hypogonadism indicated that AndroGelO quickly raised circulating testosterone to desirable levels, and maintained it within normal range. The study also found that AndroGelO increased sex drive, bone mineral density, and lean body mass and improved mood and energy levels.
“Research supporting the use of AndroGelO is extremely solid and the unique gel delivery method is very versatile,” said Ronald S. Swerdloff, M.D., Chief and Professor of Medicine, Division of Endocrinology at Harbor-UCLA Medical Center. “Testosterone deficient men who use AndroGelO can experience physical and psychological benefits with this convenient, well-tolerated gel.”
Safety data from clinical studies of AndroGelO demonstrate it to be well tolerated. Androgens are contraindicated in men with carcinoma of the breast, or known or suspected carcinoma of the prostate. Geriatric patients treated with androgens may be at an increased risk for the development of prostatic hyperplasia and prostatic carcinoma. AndroGelO is not indicated for use in women and has not been evaluated in women. Pregnant women should avoid skin contact with AndroGelO application sites in men. Testosterone may cause fetal harm.
Studies have shown that during vigorous skin to skin contact some of the testosterone in AndroGelO can be transferred to the untreated individual. Residual testosterone on the skin can be removed with soap and water. Testosterone should not be used to improve athletic performance.
For full prescribing information, physicians and patients may visit www.Unimed.com or call 1-877-463-7645.
Unimed Pharmaceuticals, Inc., a wholly owned subsidiary of Solvay Pharmaceuticals, Inc., focuses on drugs with multiple indications in the therapeutic areas of hypertension, endocrinology, urology, HIV and other infectious diseases.
Unimed currently markets TevetenO (eprosartan mesylate) for the treatment of hypertension, Marinol (dronabinol) as an appetite stimulant for people living with HIV disease and as an antiemetic for people with cancer, AnadrolO-50 (oxymetholone) for the treatment of various anemias, and MaxaquinO (lomefloxacin HCl), a broad-spectrum quinolone antibiotic, for both complicated and uncomplicated urinary tract infections.
Solvay Pharmaceuticals, Inc. of Marietta, Georgia, is a research-based pharmaceuticals company, active in the therapeutic areas of cardiology, gastroenterology, mental health and women’s health. It is a member of the worldwide Solvay Group of chemical and pharmaceutical companies, headquartered in Brussels, Belgium.
株式会社メドレット Medlet Japan KK
〒103-0024 東京都中央区日本橋小舟町１２−１０共同ビル（掘留）５Ｆ 久永&Co気付
tel.03-3664-2020 fax.03-3666-3188 URL:www.medmk.com/mm/ E-Mail: support@medmk.com
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- 0975★12/11★96.05.21★049★性機能低下に対するテストステロンパッチ
- 0985★12/21★96.10.11★091★デヒドロエピアンドロステロン(DHEA)
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- 作成：2000.7.11 最終更新:2011.11.21 小菅博之
The Medical Letter日本語版
●追加メモ to 1080,1164,1362,,1368
On Drugs and Therapeutics
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