Role of Pharmacotherapy

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Treatment of Sexual Dysfunction in Women

When education, lifestyle, communication, and behavioral changes do not achieve the desired level of success, pharmacological therapy can be utilized to treat sexual dysfunction in women.

Estrogen

Estrogen replacement therapy (ERT) may positively affect sexual function in a number of ways. Estrogens rapidly restore the superficial cell layer of the vaginal epithelium, reestablish elasticity, restore the balance in vaginal pH, improve mood, and increase blood flow to enhance lubrication. Short-term studies of estrogen replacement therapy have confirmed a benefit in some postmenopausal women with sexual dysfunction. However, not all studies have demonstrated positive results, possibly because women most likely to respond are those with symptoms of hypoestrogenism. Any short-term positive effect of oral estrogen may diminish in long-term use because of increasing sex hormone binding globulin (SHBG) levels, which lead to reduced estrogen and androgen bioavail-ability, and consequent decreased desire and activity. The increase in SHBG appears to be less significant in women who use non-oral delivery system for ERT. Vaginal estrogen is highly effective for treating genitourinary atrophy symptoms, in particular, the vaginal dryness and dyspar-eunia. Water-soluble lubricants are also helpful for continued sexual activity.

Progestin

Progestin agents downregulate the estrogen receptor, a desired result in the endometrium, but potentially undesirable in the brain, heart, bone, and genitalia. Progestins generally have an overall negative effect in the central nervous system (CNS) with respect to depression and mood, and have been shown to decrease sexual desire and diminish vaginal blood flow. Available options include micronized progesterone (MP) and 19-nortestosterone derivatives, norethindrone acetate (NA), and norgestimate (NGM). When estrogen is given with progestin, the effect on SHBG depends upon the type of progestin used. 19-nortestosterone-derived progestins decrease the SHBG levels. Newer studies in progress with more modern combinations of progestin with estrogen and androgens will provide better insight into the progestational effects on sexuality.

Androgens

Androgens play an important role in physiologic aspects of the female sexual response. However, the effect of androgen therapy on sexual function in women is controversial. Some studies have reported improvements in libido, sexual arousal, and the frequency of sexual fantasies with testosterone therapy in a variety of forms. The observation that testosterone therapy may result in improvement in mood and well-being is felt by some researchers to be most important. The central sex ster-oid's effect on mood may be what underlies sexual function in both women and men. Potential side effects of androgens include a decline in serum high-density lipoprotein (HDL) cholesterol with oral preparations and mild cosmetic side effect such as hirsutism and acne. Testosterone preparations include creams, gels, and tablets that can be taken orally or used sublingually. They are not approved in the US FDA, but one product approved in Europe for postmenopausal women is a transdermal testosterone patch. Many clinicians have tried creams that are used for vulvar dystrophies made up with 2% testosterone propionate. Others have tapered down the potency using micronized testosterone 0.5% up to 1%, and rarely 2%. Creams were applied first on the inside of the forearms or thighs, while later para-clitoral use became common. The creams seemed to work better paraclitorally in patients with sexual arousal disorder than in those with hypoactive sexual desire disorder. Studies on the use of dehydroepiandosterone (DHEA) have shown an increase in energy level, well-being, sexual satisfaction, and sexual function only in women with primary and secondary adrenal insufficiency. There are no receptors for DHEA and side effects occur due to conversion to testosterone and then to estrogen. Combination therapy with oral estrogen and methyltestosterone also improved sexual interest/desire in postmenopausal women who were experiencing hypoactive sexual desire. The data that androgen therapy significantly improves sexual functioning are suggestive, but not conclusive. No guidelines for androgen therapy for female sexual dysfunction are available. Women most likely to benefit from androgen therapy are probably

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