低劑量DHEA能增加更年期的男性荷爾蒙與雌激素濃度


  Dec. 12, 2003--根據一項發表於十二月份生殖與不孕期刊的前瞻性病例研究結果顯示,低劑量dehydroepiandrosterone(脫氫表雄甾酮,DHEA)的治療能增加早期與晚期更年期的腎上腺激素血漿濃度。
  
  義大利Modena大學的Alessandro D. Genazzani醫師及同事表示,雖然尚未考慮過以補充DHEA作為藥物治療,這種類固醇已被證實在更年期婦女中能誘導特異性代謝作用及增加男性荷爾蒙與雌激素的血漿濃度。
  
  義大利研究團隊選擇20位健康、年齡為50到65歲、沒有使用荷爾蒙補充療法的更年期病患,作為12個月的前瞻性研究,所有病患在研究開始之前皆接受超音波檢查及乳房X光攝影以排除器官疾病。
  
  Genazzani醫師和同事將病患依年齡分成二組,早期(50-55歲, n=10,A組)為二到三年的更年期、與晚期(60-65歲, n=10,B組)為更年期五年以上,其中五位女性是輕度吸煙者。
  
  所有病患連續12個月服用25mg/ day 的DHEA補充,試驗期間每三個月,調查人員評估病患並取血液樣本以測量LH、FSH、E2、DHEA、DHEAS、雄烯二酮(A)、睪固酮、二氫睪固酮、黃體激素、17α羥基黃體酮(17-OHP)、allopregnanolone、雌素酮(E1)、性荷爾蒙黏球蛋白(SHBG)、皮質醇(F)、beta-腦啡、生長激素(GH)及類胰島素成長因子-1 (IGF-1)的血漿濃度。
  
  調查人員也在治療之前與之後的6個月及12個月對每位病患實行陰道超音波檢查以評估子宮內膜厚度,此外,研究人員實施Kupperman問卷以評估治療之前與之後3、6和12個月主觀的血管收縮和心理學症狀。
  
  較年輕的更年期實驗對象(A組)顯示DHEA、DHEAS、睪固酮和beta-腦啡濃度高於較老的實驗對象 (P<.05),在治療同時也觀察到內分泌濃度的顯著變化,DHEA治療排除了研究一開始在兩組間所觀察到的內分泌差異。
  
  睪固酮和二氫睪固酮血漿濃度,與血漿中E1及E2濃度在兩組皆有明顯且逐漸地增加,調查人員發現儘管A與E的血中濃度有明顯變化,SHBG的濃度在兩組中都沒有任何改變,而兩組的Allopregnanolone和beta -腦啡濃度皆有明顯地增加。
  
  Cortisol F血漿濃度在研究期間逐漸減少,兩組的LH與FSH濃度也顯著地降低,GH和IGF-1濃度在兩組之中顯著增加,DHEA的補充不會引起子宮內膜厚度的改變。
  
  在研究一開始,A組在主觀血管收縮失調和心理學失調方面比起B群有較高的數值,反之後者在心理性變項有較高的分數,在治療期間兩組的分數都有明顯地改善。
  
  Genazzani醫師和同事表示,目前的研究顯示低劑量DHEA對於早期及晚期更年期的內分泌與精神官能內分泌參數的功效,同時證實補充低劑量DHEA能增加腎上腺男性荷爾蒙血漿濃度(主要為DHEA與DHEAS),其在更年期顯著受損。
  
  他們補充說明這些資料支持並證實需考慮將DHEA作為更年期婦女荷爾蒙療法中有效的化合物與藥物而並非只是飲食方面的補充。

Low-Dose DHEA Increases Androg

By Mindy Hung, Medical Writer
Medscape Medical News

Dec. 12, 2003 — Low-dose dehydroepiandrosterone (DHEA) administration increases adrenal hormone plasma levels in early and late menopause, according to results of a prospective case study published in the December issue of Fertility and Sterility.

"Although DHEA supplementation is not yet considered a medical treatment, this steroid has been demonstrated to induce specific metabolic effects and to increase both androgen and estrogen plasma levels in postmenopausal women," write Alessandro D. Genazzani, MD, PhD, and colleagues from the University of Modena in Italy.

The Italian team selected 20 healthy, postmenopausal patients, age 50 to 65 years, who were not using hormone replacements, for the 12-month prospective study. All patients received an ultrasound examination and a mammogram before the start of the study to exclude organic disease.

Dr. Genazzani and colleagues divided patients by age into two groups: early (aged 50-55 years, n = 10, group A) who were two to three years postmenopausal; and late (aged 60-65 years, n = 10, group B) who were five or more years postmenopausal. Five of the women were mild smokers.

All patients took 25 mg/day DHEA supplementation for 12 months. Every three months throughout the trial period, the investigators evaluated patients and drew blood samples to determine plasma levels of LH, FSH, E2, DHEA, DHEAS, androstenedione (A), testosterone, dihydrotestosterone, progesterone, 17 alpha-hydroxyprogesterone (17-OHP), allopregnanolone, estrone (E1), sex-hormone binding globulin (SHBG), cortisol (F), beta-endorphin, growth hormone (GH), and insuline-like grown factor-1 (IGF-1).

Investigators also conducted a transvaginal ultrasound examination in each patient before and after 6 and 12 months of treatment to evaluate endometrial thickness. In addition, the researchers administered a Kupperman questionnaire to evaluate subjective vasomotor and psychological symptoms before and after 3, 6, and 12 months of therapy.

Younger postmenopausal subjects (group A) demonstrated higher levels of DHEA, DHEAS, testosterone, and beta-endorphin levels than older subjects (P < .05). Significant changes in endocrine levels were observed with therapy. DHEA treatment eliminated endocrine differences observed between the two groups at baseline.

Testosterone and dihydrotestosterone plasma levels, and plasma E1 and E2 levels increased significantly and progressively in both groups. Investigators found no changes in SHBG concentrations in either group despite significant changes in A and E plasma concentrations. Allopregnanolone and beta-endorphin concentrations significantly increased in both groups.

Cortisol F plasma levels progressively decreased throughout the study. Both groups also experienced significantly reduced LH and FSH plasma levels. GH and IGF-1 levels significantly increased in both groups. Supplementation did not induce changes in endometrial thickness.

At baseline, group A had higher values for subjective vasomotor disturbances and psychological disturbances than group B, whereas the latter had a higher score for psychological variables. Scores significantly improved in both groups during therapy.

"The present study demonstrates the efficacy of low-dose DHEA administration of endocrine and psychoneuroendocrine parameters in early and late menopause and confirms that a low-dose DHEA supplementation increases adrenal androgens plasma levels (mainly DHEA and DHEAS), which are significantly impaired during menopause," Dr. Genazzani and colleagues write.

"These data support and confirm that DHEA must be considered a valid compound and drug for [hormone therapy] in postmenopausal women and not just a 'dietary supplement,' " they add.

Fertil Steril. 2003;80:1495-1501

Reviewed by Gary D. Vogin, MD

    
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