Agent shows promise for female sexual dysfunction

Women who took bremelanotide (formerly, PT-141) in a small trial reported significantly higher levels of sexual desire than did women in a placebo group.

"Some women were initiating sex who had never initiated it before," said Michael A. Perelman, PhD, co-director of the human sexuality program at New York Presbyterian Hospital/Weill Cornell, who presented an update on the drug at the Sexual Medicine Society of North America meeting here.

"It's a small study and the outcomes are limited, but it shows promise," commented Culley Carson, MD, chief of urology at the University of North Carolina, Chapel Hill.

Bremelanotide differs from the sexual dysfunction drugs on the market for men in that it acts on the central nervous system, rather than on the circulatory system. It is a synthetic peptide analog of alpha-melanocyte stimulating hormone and an agonist at melanocortin receptors MC3R and MC4R. It is currently in phase II clinical trials for erectile dysfunction, and experiments in men have so far shown significant erectile activity.

"Despite the gender differences, there are signals suggesting bremelanotide may be helpful to women with FSD," Dr. Perelman said.

In preclinical studies, ovariectomized female rats showed an increase in such behaviors as solicitations, hops and darts, lordosis, and female mounts. It's unclear, though, how reliably these behaviors indicate sexual desire or arousal.

Investigators followed up this animal study with a double-blind, placebo-controlled trial in 32 healthy women who took either a subcutaneous injection of 0.3 mg, 1.0 mg, 3.0 mg, or 5.0 mg of bremelanotide or a placebo. The women then watched a neutral video, followed by an erotic video. Vaginal pulse amplitude (VPA) was measured through vaginal photoplethysmography. The drug was well tolerated, and the women who had taken the bremelanotide showed a greater increase in VPA over baseline than did the women who took the placebo.

Increased desire over placebo

Investigators, including Dr. Perelman, then enrolled 18 premenopausal women with a primary diagnosis of female sexual arousal disorder in a double-blind, placebo-controlled cross-over trial. The women took either two 10-mg puffs of intranasal spray or a matching placebo during the first treatment session, then they switched 2 to 7 days later. Five minutes after each treatment, the women watched a neutral video for 20 minutes, then, 10 minutes later, a sexually explicit video.

Afterward, they completed the Treatment Satisfaction Index, a 14-item self-administered questionnaire. Of the women taking bremelanotide, 67% reported feelings of desire, while only 22% of those using the placebo experienced such feelings (p=.0114). Nearly three-fourths (72%) of those in the active treatment group experienced genital arousal, versus 39% in the placebo group (p=.0833), and among those women who attempted sexual intercourse within 24 hours after treatment, significantly more were satisfied with their level of arousal (p=.0256).

Five of the 18 women reported mild nausea, and three reported a mild head-ache. These reactions resolved without intervention. VPA did not change significantly, a finding that is not surprising in light of the fact that bremelanotide acts on the central nervous system, rather than on the circulatory system, Dr. Carson pointed out.

In a group of postmenopausal women who followed the same protocol, the data were still being analyzed when Dr. Perelman gave his presentation. Preliminary results showed that 75% of the women taking bremelanotide reported arousal, and 50% reported desire, compared to 25% and 19%, respectively, of placebo recipients.