No abstract

Various parameters of sexual functioning were assessed in a prospective, crossover investigation of 53 surgically menopausal women. Patients randomly received either an estrogen-androgen combined preparation, an estrogen-alone drug, an androgen-alone drug, or a placebo. Also included were a group of women who had undergone hysterectomy and whose ovaries had been left intact. Two treatment phases, each of 3 months' duration, were separated by an intervening placebo month. Additionally, plasma levels of total estrogens and testosterone were assayed four times during the study concurrent with monitoring of sexual behaviors. It was clear that exogenous androgen enhanced the intensity of sexual desire and arousal and the frequency of sexual fantasies in hysterectomized and oophorectomized women. However, there was no evidence that testosterone affected physiologic response or interpersonal aspects of sexual behavior. These findings suggest that the major impact of androgen in women is on sexual motivation and not on sexual activity per se.

Estrogen is an active neuroprotectant and is presently investigated as a potential therapy against Alzheimer's disease for women. To determine if male hormones could also be neuroprotective, we investigated the effect of testosterone, methyltestosterone, and epitestosterone at physiological concentrations on primary cultures of human neurons induced to undergo apoptosis by serum deprivation. Serum deprivation signi®cantly induces neuronal apoptosis in a protracted fashion. As expected, physiological concentrations of 17-bestradiol and transcriptionally inactive 17-a-estradiol protect neurons against apoptosis. Similar to 17-b-estradiol, physiological concentrations of testosterone are also neuroprotective. Androgen receptors are present at 8^2 fmol/mg protein in the neuron cultures. The non-aromatizable androgen, mibolerone, is also neuroprotective and aromatase inhibitor, 4-androsten-4-OL-3,17-dione, does not prevent testosteronemediated neuroprotection. In contrast, anti-androgen,¯utamide, eliminates testosterone-mediated neuroprotection. Testosterone analog, methyltestosterone, showed androgen receptordependent neuroprotection that was delayed in time indicating that a metabolite may be the active agent. The endogenous anti-androgen, epitestosterone, also showed a slight neuroprotective effect but not through the androgen receptor. These results indicate that androgens induce neuroprotection directly through the androgen receptor. These data suggest that androgens may also be of therapeutic value against Alzheimer's disease in aging males.

Five aspects of sexual behavior were monitored daily in three groups of women who had undergone total abdominal hysterectomy and bilateral salpingo-oophorectomy approximately 4 years ago for benign disease. One group had been receiving an estrogen-androgen preparation intramuscularly once a month since their surgery (E-A). The second group had been receiving estrogen alone (E) and the third group of women had remained untreated. Plasma estradiol and testosterone were measured at an established baseline and again on days 2, 4, 8, 15, 21, and 28 postinjection. Women who received both sex steroids reported higher rates of sexual desire (p less than 0.01), sexual arousal (p less than 0.01), and numbers of fantasies (p less than 0.01) than those who were either given E or who were untreated. Moreover, changes in these behaviors covaried with plasma testosterone but not with plasma estradiol levels during the treatment month as the drug was being metabolized. Rates of coitus and orgasm were also higher in the E-A group during the first two postinjection weeks (p less than 0.01) coincident with their higher testosterone levels. These findings imply that androgen may be critical for the maintenance of optimal levels of sexual functioning in postmenopausal women.