Efficacy and safety of low-dose regimens of conjugated estrogens cream administered vaginally.

OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of low-dose conjugated estrogens (CE) cream for treatment of atrophic vaginitis. METHODS: Postmenopausal women (N = 423) with moderate-to-severe vaginal atrophy were randomized to CE cream 0.3 mg or placebo once daily (21 days on/7 days off) or twice weekly for 12 weeks, followed by open-label treatment with CE cream for 40 weeks consistent with their prior regimen. Primary endpoints were changes in vaginal maturation index (VMI; percentage of superficial cells), vaginal pH, and severity of participant-reported most bothersome symptom (vaginal dryness, itching, burning, or dyspareunia) at week 12. Endometrial safety was assessed by transvaginal ultrasound and endometrial biopsy for 52 weeks. RESULTS: At week 12, improvements in VMI with daily and twice-weekly use of low-dose CE cream (27.9% and 25.8%, respectively) were significantly greater compared with placebo (3.0% and 1.0%, respectively; P < 0.001). Improvements in vaginal pH with daily and twice-weekly CE cream (-1.6 for both) were also significantly greater relative to placebo (-0.4 and -0.3, respectively; P < 0.001). VMI and vaginal pH responses were sustained through 52 weeks. Both CE cream regimens significantly reduced most bothersome symptom scores compared with placebo (P < or = 0.001), including those for dyspareunia (P < or = 0.01). There was no report of endometrial hyperplasia or carcinoma. Adverse events occurred with similar frequency among the active and placebo groups during the double-blind phase. CONCLUSIONS: Daily and twice-weekly use of low-dose CE cream was equally effective in relieving symptoms of vulvovaginal atrophy. Both regimens showed endometrial safety and sustained efficacy during 1 year of therapy.

A randomized study of low-dose conjugated estrogens on sexual function and quality of life in postmenopausal women.

OBJECTIVE: To evaluate the effects of combined vaginal and oral low-dose estrogen plus progestogen therapy (EPT) on the frequency and severity of dyspareunia, sexual function, and quality of life in recently postmenopausal women. METHODS: This outpatient, double-blind, randomized, placebo-controlled trial enrolled 285 healthy, sexually active postmenopausal women aged 45 to 65 years. Women received either one daily oral low-dose conjugated estrogens (0.45 mg)/medroxyprogesterone (1.5 mg) tablet for six 28-day cycles along with 1 g conjugated estrogens vaginal cream (0.625 mg), intravaginally for the first 6 weeks of the trial or a placebo cream and placebo tablet. Efficacy was evaluated using the McCoy Female Sexuality Questionnaire, self-reported daily diary cards, the Brief Index of Sexual Functioning-Women (BISF-W), and the Women's Health Questionnaire. RESULTS: The EPT group had a significant decrease in the frequency of dyspareunia compared with baseline and placebo in an analysis of responses to the McCoy Female Sexuality Questionnaire. Also, EPT was associated with a significant improvement in a woman's level of sexual interest, frequency of orgasm, and pleasure of orgasm. There was no effect of EPT use on coital frequency. The EPT group had significant improvement in receptivity/initiation and relationship satisfaction, although not in other BISF-W domains, versus placebo (BISF-W analysis) and significant improvement versus placebo on most Women's Health Questionnaire responses. CONCLUSIONS: EPT provided a statistically significant improvement compared with placebo in dyspareunia, sexual experience, and quality of life as measured in this study. In general, EPT also improved self-reported sexual perception and enjoyment significantly compared with placebo.