Pharmacologically induced hypogonadism and sexual function in healthy young women and men

Abstract

Studies fail to find uniform effects of age-related or induced hypogonadism on human sexual function. We examined the effects of induced hypogonadism on sexual function in healthy men and women and attempted to identify predictors of the sexual response to induced hypogonadism or hormone addback. The study design used was a double-blind, controlled, crossover (self-as-own control). The study setting was an ambulatory care clinic in a research hospital, and the participants were 20 men (average+/-SD age=28.5+/-6.2 years) and 20 women (average+/-SD age=33.5+/-8.7 years), all healthy and with no history of psychiatric illness. A multidimensional scale assessing several domains of sexual function was the main outcome measure. Participants of the study received depot leuprolide acetate (Lupron) every 4 weeks for 3 months (men) or 5 months (women). After the first month of Lupron alone, men received (in addition to Lupron) testosterone enanthate (200 mg intramuscularly) or placebo every 2 weeks for 1 month each. Women received Lupron alone for 2 months, and then, in addition to Lupron, they received estradiol and progesterone for 5 weeks each. The results of the study: in women, hypogonadism resulted in a significant decrease in global measures of sexual functioning, principally reflecting a significant decrease in the reported quality of orgasm. In men, hypogonadism resulted in significant reductions in all measured domains of sexual function. Testosterone restored sexual functioning scores in men to those seen at baseline, whereas neither estradiol nor progesterone significantly improved the reduced sexual functioning associated with hypogonadism in women. Induced hypogonadism decreased sexual function in a similar number of men and women. No predictors of response were identified except for levels of sexual function at baseline. In conclusion, our data do not support a simple deficiency model for the role of gonadal steroids in human sexual function; moreover, while variable, the role of testosterone in sexual function in men is more apparent than that of estradiol or progesterone in women.

Figures

Figure 1

All women received 3.75 mg of depot Lupron (leuprolide acetate; TAP Pharmaceuticals, Chicago, IL) by intramuscular injection every 4 weeks for 5 months. The first injection of Lupron was administered during the follicular phase between days 2–6 after the onset of menses. Lupron alone was administered for the first 8 weeks. All women then received, in addition to Lupron, 17 β estradiol (0.1 mg/day) (E) by skin patch (Alora; Watson Pharmaceuticals, Salt Lake City, UT) or progesterone suppositories (200 mg b.i.d.) (P) (NIH Pharmacy, Bethesda, MD) for 5 weeks each. The two replacement regimens were separated by a 2-week washout period. Subjects were administered both patches and suppositories (active or placebo, depending upon the treatment phase) daily throughout the entire replacement period to ensure that the double blind was maintained. During the last week of E, all women received 1 week of active P suppositories in addition to E to precipitate menses. All women received prepackaged 1-week unit-dose supplies of suppositories that were formulated and coded (weeks 1–5) by the NIH Pharmacy Department. All men received 7.5 mg of depot Lupron by intramuscular injection every 4 weeks for 3 months. Lupron alone was administered for the first 4 weeks. Subjects then received, in addition to Lupron, testosterone enanthate (200 mg) or placebo (1 ml sesame oil) given by intramuscular injection every 2 weeks for 1 month. All men received 1 month each of testosterone replacement (T) and placebo. A placebo comparison was included in men to blind the timing of the addition of testosterone, whereas in women no placebo phase was included since the order of estradiol and progesterone addback was randomly assigned. In both men and women the order of receiving hormone replacement (ie, T vs placebo in men, and E vs P in women) was randomly assigned and counter-balanced.

Figure 2

In men, a significant interaction between baseline symptom group (high vs lo,w) and hormone condition was identified by ANOVA-R (F2,20 = 9.7, p < 0.003). Men with high baseline DISF scores (n = 6) had a significant reduction in total DISF scores during hypogonadism compared with both baseline and T-replaced conditions, and a significant increase in DISF scores after T replacement compared with hypogonadism. Men with low baseline DISF scores (n = 6) showed no significant differences in DISF scores across hormone conditions. Similarly, women with high baseline DISF scores (n = 6) showed a significant reduction in DISF scores during hypogonadism (and during estrogen and progesterone conditions) compared with baseline scores, whereas women with low baseline DISF scores (n = 6) showed no significant change across hormone conditions (ANOVA-R group × hormone condition, F3,30 = 9.8, p = 0.001). In women, total DISF scores were significantly greater in the ‘high’ group at baseline only (t40 = 3.8, p < 0.01; otherwise p = NS). Whereas, in men, total DISF scores were significantly higher in the ‘high’ compared to the ‘low’ baseline symptom group during both baseline and T (t30 = 3.4 and 4.7, respectively, p < 0.01). No significant interactions between subscale scores and group or hormone condition were observed in either men or women.