The primary symptoms of menopause are genitourinary (genitourinary syndrome of menopause; GSM) and vasomotor (VMS). Vulvovaginal atrophy can cause vaginal burning, irritation and dryness, dyspareunia, and dysuria, and increase the risk of urinary tract infections. Vasomotor symptoms ("hot flashes") cause daytime discomfort and night sweats that may disrupt sleep. Hormone therapy is the most effective treatment for both genitourinary and vasomotor symptoms.

The FDA has approved an estradiol softgel vaginal insert (Imvexxy – TherapeuticsMD) for treatment of postmenopausal women with moderate to severe dyspareunia due to vulvovaginal atrophy (VVA). Imvexxy is the second estradiol vaginal insert to be approved in the US; Vagifem, an intravaginal tablet formulation, was the first. Vagifem and Imvexxy are both available in inserts containing 10 mcg of estradiol; Imvexxy is also available in a 4-mcg strength.

The FDA has approved the steroid prasterone (Intrarosa – Endoceutics) for intravaginal treatment of postmenopausal women with moderate-to-severe dyspareunia due to vulvovaginal atrophy (VVA). Also called dehydroepiandrosterone (DHEA), prasterone is produced in the adrenal glands, gonads, and brain and converted intracellularly into active metabolites of estrogens and androgens. DHEA has been available over the counter for years as an oral dietary supplement claimed to benefit sexual, cardiovascular, and neuropsychiatric dysfunction.

Some readers have objected to our recommendation (Med Lett Drugs Ther 2013; 55:55) that postmenopausal women with an intact uterus who take the oral estrogen agonist/antagonist ospemifene (Osphena) to reduce the severity of dyspareunia should also take a progestin.1 Ospemifene has agonistic effects on the endometrium, and the Osphena package insert says: "Generally, when a product with estrogen agonistic effects on the endometrium is prescribed for a postmenopausal woman with a uterus, a progestin should be considered to reduce the risk of endometrial cancer."

Endometrial hyperplasia has been reported in more than 20% of women taking unopposed systemic estrogen for more than one year; the risk is closely related to the dose and duration of treatment. Adding a progestin to estrogen therapy in women with a uterus reduces the risk of endometrial hyperplasia and cancer, but has been associated with an increased risk of invasive breast cancer and thromboembolic events.2

In ospemifene clinical trials, the drug was taken without a progestin and at 1 year there were no cases of endometrial hyperplasia or carcinoma, but only a small number of women took the drug for more than 12 weeks. These studies excluded women with an endometrial thickness of ≥4 mm detected by transvaginal ultrasound, pathological findings on endometrial biopsy or Pap test, or any other clinically significant gynecological abnormality. They also excluded women who were obese or had hypertension, among many other exclusions.

It is possible that the estrogenic effects of ospemifene on the endometrium will prove to be similar to those of the estrogen agonist/antagonist raloxifene (Evista), which has not increased the incidence of endometrial cancer.3 For now, it would not be unreasonable for postmenopausal women with an intact uterus who can be followed closely for vaginal bleeding or spotting and do not have risk factors for endometrial cancer (obesity, hypertension, diabetes, nulliparity) to take ospemifene without a progestin. For all others, a progestin should be considered.

1. Ospemifene (Osphena) for dyspareunia. Med Lett Drugs Ther 2013; 55:55.

2. JE Manson et al. Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women's Health Initiative randomized trials. JAMA 2013; 310:1353.

3. SR Goldstein. Postmenopausal dyspareunia: has the Food and Drug Administration really helped? Menopause 2013; 20:596.

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The FDA has approved ospemifene (os pem’ i feen; Osphena – Shionogi), an estrogen agonist/antagonist, for oral treatment of moderate to severe dyspareunia in postmenopausal women. Ospemifene is the fourth estrogen agonist/antagonist to be marketed in the US, but it is the only one that has an estrogen-like effect on vaginal epithelium. The other three, tamoxifen (Nolvadex, and generics), toremifene (Fareston), and raloxifene (Evista), are used for treatment and prevention of breast cancer and osteoporosis.

Sexual complaints related to desire, arousal, orgasm and painful intercourse are common in women. Since the last Medical Letter article on this subject, some new information has become available.

An old conjugated estrogens vaginal cream (Premarin Vaginal Cream - Wyeth) has been newly approved by the FDA specifically for treatment of moderate to severe dyspareunia due to vulvar and vaginal atrophy associated with menopause. Synthetic conjugated estrogens A vaginal cream (Barr) has also been approved for this indication, but has not yet been marketed.