Testosterone dose-response relationships in hysterectomized women with or without oophorectomy

Abstract

Objective To determine dose-dependent effects of testosterone on sexual function, body composition, muscle performance, and physical function in hysterectomized women with and without oophorectomy. Methods 71 menopausal women who previously underwent hysterectomy with or without oophorectomy with total testosterone<31ng/dl or free testosterone<3.5 pg/ml received a standardized transdermal estradiol regimen during the 12-week run-in period, and were then randomized to receive weekly IM injections of placebo, or 3, 6.25, 12.5 or 25 mg testosterone enanthate for 24 weeks. Total and free testosterone levels were measured by LC-MS/MS and equilibrium dialysis, respectively. The primary outcome was change in sexual function measured using Brief Index of Sexual Function (BISF-W); Secondary outcomes included changes in sexual activity, sexual distress, DeRogatis Inventory of Sexual Function, lean (LBM) and fat mass, muscle strength and power, and physical function. Results 71 women were randomized; five groups were similar at baseline. 62 women with analyzable data for the primary outcome were included in the final analysis. Mean on-treatment total testosterone concentrations were 19, 78, 102, 128 and 210ng/dl in the placebo, 3, 6.25, 12.5 and 25-mg groups, respectively. Changes in composite BISF-W scores, thoughts-desire, arousal, frequency of sexual activity, LBM, chest-press power and loaded stair-climb power were significantly related to increases in free testosterone concentrations; changes were significantly greater in women assigned to the 25-mg group when compared to placebo but not at the lower dose groups. Sexual activity increased by 2.7 encounters per week in 25-mg group. Frequency of androgenic adverse events was low. Conclusion Testosterone administration in hysterectomized women with and without oophorectomy for 24-weeks was associated with dose and concentration-dependent gains in several domains of sexual function, LBM, chest-press power and loaded stair-climb power. Long-term trials are needed to weigh improvements in these outcomes against potential long-term adverse effects.

Testosterone and Adipokines are Determinants of Physical Performance, Strength, and Aerobic Fitness in Frail, Obese, Older Adults

“…Huang et al reported dose-related increases in lean body mass and improvement in strength [32] in postmenopausal women with low gender-adjusted testosterone suggesting the potential for testosterone to improve body composition and physical function in women. Their results were supported by data from another recent study showing that muscle protein synthesis in postmenopausal women is actually stimulated by testosterone and progesterone but not by estradiol [33].…”

Female hyperandrogenism and elite sport

“…The sparsity of research investigations on the effects of exogenous testosterone on the physical performance of women probably reflects the ethical concerns about potential adverse effects. In one study on postmenopausal women, administration of different doses of testosterone (reaching a maximal mean circulating level of 7.3 nmol/L) for 24 weeks resulted in dose-dependent increases in mean muscle mass by as much as 4.4% and in muscle strength by 12-26% (54).…”

A biopsychosocial approach to women’s sexual function and dysfunction at midlife: A narrative review

“…A black box warning was recently added to testosterone products marketed to men after a longitudinal study suggested a 30% higher risk of adverse cardiovascular outcomes (75), although this study has been criticized due to methodology concerns (76-79), and whether it is generalizable to women is unknown. Finally, it appears supraphysiological serum testosterone levels may be necessary to yield any benefit on sexual desire and arousal (80, 81). The use of compounded testosterone products for transdermal use is on the rise, but these products are not regulated and amount of testosterone in the product can be highly inconsistent (82).…”