Abstract Introduction Although Hypoactive Sexual Desire Disorder (HSDD) is a common condition with a relevant impact on women’s quality of life, approved androgenic formulations for its treatment are lacking. In previous studies, we demonstrated that the administration of Dihydrotestosterone (DHT), a non-aromatizable androgen, in ovariectomized (OVX) Long-Evans rats primed with Estradiol Benzoate (EB), enhanced measures of sexual behavior. Objective To further clarify the mechanisms underlying the facilitating action of testosterone on female sexual function by investigating the effect of AR (androgen receptor) activation in a validated animal model. Methods After sexual training and hormonal wash-out, OVX Long-Evans rats were treated with different hormonal regimens: oil (O) + O (negative control group), 10 mcg EB+500 mcg Progesterone (P) (positive control group), 10 mcg EB+500 mcg DHT, and 10 mcg EB+500 mcg DHT+10 mg flutamide (FLU), a nonsteroidal AR antagonist (n=4 per group). EB was administered s.c. 48 h, P and DHT s.c. 4 h, and flutamide i.m. 48 and 24h prior to video-recorded sexual behavioral testing sessions. These took place in bisected unilevel pacing chambers, with sexually experienced males. Five testing sessions were conducted every 8 days. The main outcome measures were appetitive behaviors: the number of hops/darts (partial solicitation), full solicitations and olfactory investigations. Results A significant difference emerged among the 4 groups for all the outcome measures. Regarding solicitations, animals treated with EB+DHT displayed a higher number of hops/darts and full solicitations than the negative control group (O+O), although significantly lower than the positive control group (EB+P) for hops/darts (p=0.025). As a novel finding, we observed that the stimulating effect of EB+DHT was blunted in rats treated with EB+DHT+FLU, which showed a lower number of behaviors than EB+DHT rats (p=0.014 for hops/darts, and p=0.083, approaching statistical significance, for full solicitations). Interestingly, a significant difference was detected in the frequency of olfactory investigations, with the EB+DHT group displaying a higher frequency not only when compared with O+O rats (p=0.047), but also with EB+DHT rats (p=0.047 for both comparisons). Once again, the co-administration of FLU significantly reduced the stimulating effect (p=0.005 for olfactory investigations for EB+DHT+FLU vs. EB+DHT). Conclusions These data, to be confirmed in larger samples, indicate that the positive modulation exerted by androgens on appetitive behaviors, homologous to sexual interest in women, are independent of aromatization. In addition, a specific stimulating effect was detected for olfactory investigations. Disclosure No
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