Estrogen and estrogen-androgen replacement in postmenopausal women dissatisfied with estrogen-only therapy. Sexual behavior and neuroendocrine responses

J Reprod Med. 1998 Oct;43(10):847-56.


Objective: To investigate the efficacy of esterified estrogens alone and combined with oral androgen on sexual function and menopausal symptoms in postmenopausal women.

Study design: Twenty postmenopausal women dissatisfied with their estrogen or estrogen-progestin therapy volunteered to enter a double-blind, randomized trial in which they received either oral esterified estrogens or esterified estrogens + androgen for eight weeks after a single-blind, placebo, lead-in period. Sexual function was assessed with a questionnaire used in the Yale midlife survey, and plasma levels of estradiol, estrone, sex hormone binding globulin (SHBG) and beta-endorphin were measured at two- to four-week intervals.

Results: Estrogen-androgen therapy significantly improved sexual sensation and desire after four and eight weeks of double-blind treatment in comparison to previous estrogen therapy and postplacebo baseline assessments. Plasma levels of estradiol and estrone increased significantly in all patients as compared to the postplacebo baseline and decreased in comparison to circulating estrogen concentrations on previous therapy. Relative proportions of free and bound steroid hormone exhibited contrasting shifts during estrogen and estrogen-androgen therapy. SHBG increased in the estrogen group and decreased in the estrogen-androgen group, leading to lower amounts of free androgens during estrogen therapy and increased free androgen levels during estrogen-androgen therapy. Since proportions of free (bioavailable) ovarian steroids would correlate inversely with plasma protein binding capacity, the beneficial effects of oral estrogen-androgen therapy on sexual sensation and desire may be due either to the administered androgen or to the increased availability of endogenous and exogenous androgens, particularly in the central nervous system.

Conclusion: Sexual desire, satisfaction and frequency in postmenopausal women taking hormonal therapy were improved significantly by combined estrogen-androgen therapy but not by estrogen or estrogen-progestin therapy. Sexual function improved with estrogen-androgen therapy even though circulating estrogen levels were lower than those measured during previous estrogen therapy. This leads to the conclusion that androgens play a pivotal role in sexual function but that estrogens are not a significant factor determining levels of sexual drive and enjoyment.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Double-Blind Method
  • Estrogens / administration & dosage
  • Estrogens / pharmacology*
  • Female
  • Gonadal Steroid Hormones / pharmacology
  • Hormone Replacement Therapy*
  • Humans
  • Libido / drug effects
  • Methyltestosterone / administration & dosage
  • Methyltestosterone / pharmacology*
  • Middle Aged
  • Neurosecretory Systems / drug effects*
  • Postmenopause
  • Progestins / administration & dosage
  • Progestins / pharmacology
  • Sexual Behavior / drug effects*
  • Testosterone Congeners / administration & dosage
  • Testosterone Congeners / pharmacology*


  • Estrogens
  • Gonadal Steroid Hormones
  • Progestins
  • Testosterone Congeners
  • Methyltestosterone