A little bit of the right hormone in the right place can make a world of difference in the sexual lives of post-menopausal women, as shown in two recent studies of intravaginal hormone delivery.
Very promising data from a randomized, double-blind Canadian study of intravaginal DHEA (dehydroepiandrosterone) opens the door for new options in treating sexual dysfunction in women, including one of the most difficult to treat aspects: low libido.
Two hundred eighteen postmenopausal women, aged 42-74 years, were randomized to receive either placebo intravaginal ovules, or DHEA ovules at doses of 3.25 mg, 6.5 mg or 13 mg per day. The ovules contained Prasterone in a lipophilic base manufactured by Recipharm of Sweden (www.recipharm.com). The women were instructed to insert one of the assigned ovules every day for a total of 12 weeks. The main assessment criteria were sexual dysfunction parameters of libido, arousal, orgasm and dyspareunia. Note that all of the women had vaginal atrophy at baseline.
At 12 weeks, the DHEA at all dose levels was able to attenuate signs and symptoms of atrophy. Compared with placebo, daily treatment with 13 mg DHEA resulted in a 68% mean score improvement on the arousal/sensation domain of Abbreviated Sex Function assessment scale. Mean score on the arousal/lubrication domain increased by 39%; the orgasm score improved by 75%, and dryness during intercourse by 57%. DHEA also outperformed placebo in the desire domain of the Menopause Specific Quality of Life Index, with mean scores of 49% versus 23% (Labrie F, et al. Menopause 2009;16:923-931).
I give these findings a big “Thumbs Up!” This report and a related study by the same authors, also showed that serum DHEA levels were not substantially increased during intravaginal DHEA treatment, and remained within the normal range for postmenopausal women even after 12 weeks of continuous treatment. This certainly bodes well on the systemic safety front. I will definitely be adding “13 mg DHEA intravaginal suppositories” to my compounding pharmacy prescription orders for post-menopausal patients.
Intravaginal estriol and progesterone can also be quite helpful for postmenopausal women experiencing atrophic vaginitis, as was shown in a pilot study of 19 otherwise healthy patients. They were given suppositories containing 1 mg estriol and 30 mg of progesterone, and told to use one suppository intravaginally per day for the first two weeks, followed by thrice weekly insertions for a total of 6 months. Evaluations included vaginal pH, maturation index, urinalysis, self-reported vaginal dryness, quality of life, and serum estriol and progesterone levels. The researchers also took endometrial biopsies to evaluate tissue changes.
The maturation index, vaginal pH and vaginal dryness ratings significantly improved at 3 and 6 months compared with baseline. The average maturation index improved from 40 at baseline to 57.5 at 3 months, and 55 at 6 months. Vaginal pH also improved from an average of 6.0 at baseline to 4.5.
Self-assessment of vaginal dryness improved from an average value of 9.0 at baseline to 2.0 at 3 months, and 1.0 at 6 months. Seventeen of the 19 women were sexually active and all 17 reported improvement in vaginal lubrication during sexual activity. The average values also improved for both libido and urinary frequency, two other issues related to vulvovaginal atrophy (Chollet J, et al. Menopause. 2009;16(5):978-983).
None of the women reported mastalgia, urinary tract infections, or nausea and only one woman had episodes of vaginal spotting, which occurred during the first 2 weeks of treatment.
Endometrial biopsies at 6 months showed no evidence of hyperplasia or cancer in any of the participants. Serum estriol concentrations were similar to baseline at week 2, and again at months 3 and 6, suggesting minimal systemic absorption from intravaginal application of estriol. Serum progesterone did rise significantly during the initial 2-week period of daily application, but did not continue to increase during the maintenance period.
These findings are no surprise to those of us accustomed to successfully using vaginal estriol in postmenopausal vulvovaginal atrophy. But the study does raise questions about the role of progesterone in this context.
Most practitioners do not add progesterone to their compounded estrogen vaginal suppositories, because it is generally agreed upon that use of intravaginal estrogen (whether estriol, estradiol or conjugated equine estrogens) 2-3 times weekly, is very safe for the endometrium and does not require progesterone opposition. However, there may be cases in which adding progesterone makes sense, and in which this current study can provide guidance.
