Are vaginal estradiol tablets better for VVS than OTC moisturizer or placebo?

March 27, 2018

Results of a randomized clinical trial (RCT) suggest that over-the-counter moisturizer may be just as effective as vaginal estrogen tablets for treatment of vulvovaginal symptoms (VVS) in postmenopausal women. Plus: Does a Mediterranean diet help protect bones in postmenopausal women? Also: Metformin, an oral diabetes medication, seems to reduce the likelihood of late miscarriage and premature birth in women with polycystic ovary syndrome (PCOS), according to results of a multicenter study.

Results of a randomized clinical trial (RCT) suggest that over-the-counter moisturizer may be just as effective as vaginal estrogen tablets for treatment of vulvovaginal symptoms (VVS) in postmenopausal women. Published in JAMA Internal Medicine, the findings are from a study supported by the National Institutes of Health/National Institute on Aging that focused on moderate-to-severe VVS and a 10-µg dosage of vaginal estrogen.

For the research, 302 sexually active women with a median age of 61 were randomized to vaginal estradiol in tablet form daily for 2 weeks then twice weekly plus placebo gel 3 times a week, a placebo tablet plus vaginal moisturizer (Replens), or dual placebos on the same schedule. The primary outcome was severity of most bothersome symptom (MBS), defined by each woman at trial enrollment as vulvovaginal itching, pain, dryness, irritation, or pain with penetration. The women rated MBS on a scale of 0 (none) to 3 (severe).

During the 12-week study, the participants were contacted by telephone 3 times for assessment of adherence to the protocol and adverse events. At weeks 4 and 12, follow-up visits were conducted, at which the women completed questionnaires and vaginal samples were taken and assessed on wet mount and for pH and vaginal maturation index (baseline and week 12). Rates of adherence-94% for tablets and 90% for gel-were determined by counting remaining pills and weighing gel tubes.

Pain with penetration was the MBS most commonly reported by the participants (60%), followed by vulvovaginal dryness (21%). Mean baseline MBS severity was similar between all three treatment groups (2.4 estradiol, 2.5 moisturizer, 2.5 placebo). At the end of the trial, MBS severity reductions also were similar (-1.4, 95% CI, -1.6 to -1.2 estradiol; -1.2, 95% CI -1.4 to -1.0 moisturizer; -1.3, 95% CI -1.5 to -1.1 placebo).  No significant differences were seen between estradiol (P = .25) or moisturizer (P = .31) compared with placebo. Response to estradiol was not modified by either age or years since menopause, although greater improvement in MBS was seen with placebo than with moisturizer in women aged < 60.

The authors said their results “suggest that most women can achieve greater than 50% reduction in symptom severity with regular, consistent use of a vaginal gel with lubricant properties and do not see added symptom improvement with vaginal estradiol.” Their study, they believe, is the first RCT of efficacy of nonhormonal and hormonal vaginal therapies for postmenopausal VVS and the only one with a dual-placebo arm. Generalizability of the results is limited in that the population was relatively homogenous. However, because all postmenopausal women with moderate to severe VVS were included and not just those with high vaginal pH n ad/or 5% less superficial cells, the authors believe the population is more representative of women who present in primary care settings. 

NEXT: Does a Mediterranean diet help protect bones in postmenopausal women?

 

Does a Mediterranean diet help protect bones in postmenopausal women?

According to research presented at ENDO 2018: The Endocrine Society Annual Meeting, following a Mediterranean diet may be beneficial to postmenopausal women in promoting muscle mass and higher bone mineral density (BMD). A Mediterranean diet is one that consists of a high intake of fruits and vegetables, grains, olive oil, seeds, and potatoes; moderately high fish intake; low saturated fat, dairy, and red meat consumption; and regular drinking of red wine in moderation.

The study included 103 healthy women from Brazil who had an average age of 55 years and had gone through menopause, on average, 5.5 years earlier. Participants currently taking hormone replacement therapy (HRT) were excluded. The participants underwent bone scans to measure their BMD, total body fat, and appendicular lean mass index (ALMI), which was used to estimate skeletal mass. A pedometer was used to measure habitual physical activity. Resting metabolic rate was calculated by indirect calorimetry. In addition, the participants completed a questionnaire about the food they ate during the past month. Scoring of the Mediterranean diet was based on the consumption of vegetables and legumes, fruits, olive oils, cereals, dairy products, alcohol, fish, and meat.

The researchers found that a higher Mediterranean dietary intake score had a positive association with better muscle mass vs a lower score (ALMI, 6.6 vs 6.3 kg/m2; P = .039) and greater lumbar spine BMD (1.076 vs 0.997; P = .07). Femoral neck and total femoral BMD were similar between the groups. Adjustment for potential confounders such as previous histories of smoking, HRT (prior to the study), and physical activity levels did not alter the findings.

While the researchers note that the findings are interesting, they caution that this was only an observational study and it did not compare the Mediterranean diet with other diets. More studies are needed to further clarify the effect that the Mediterranean diet has on body composition during menopause, but early evidence suggests that such a diet may be a useful nonpharmacological therapy for preventing osteoporosis and bone fractures. 

NEXT - Study: Diabetes drug may prevent PCOS complications

 

Study: Diabetes drug may prevent PCOS complications

Metformin, an oral diabetes medication, seems to reduce the likelihood of late miscarriage and premature birth in women with polycystic ovary syndrome (PCOS), according to results of a multicenter study presented at ENDO 2018, the Endocrine Society’s 100th annual meeting. However, the drug does not affect the rate at which these patients develop gestational diabetes. 

In the randomized, double-blinded, multicenter study (14 centers in Norway, Sweden, and Iceland) 487 women with PCOS were randomly assigned to receive either daily metformin (2000 mg) or an inactive placebo from their first trimester to delivery. However, six participants were not included in the final results (4 lost to follow-up and 2 violated protocol). The average age of the participants was 29 years. The primary endpoint of the study was the combined prevalence of late miscarriage and preterm birth (PTB). Secondary endpoints were prevalence of the gestational diabetes, preeclampsia and pregnancy induced hypertension, neonatal intensive care unit (NICU) admission and maternal hospitalization. Tertiary endpoints were maternal weight gain in pregnancy and newborn weight, length, and head circumference.

The researchers considered adherence “good” if at least 90% of the medication was taken, “acceptable” if it was between 70% and 90%, and “poor” if it was below 70%. During the study, 81% of the participants took 70% or more of the medication.

After excluding women who dropped out of the study, the researchers found that the combined incidence of late miscarriage and PTB was almost halved in the women receiving metformin versus placebo.  Only 9 (5%) of the 211 women who completed the study in the metformin group experienced late miscarriage or PTB. In the placebo group, 23 (10%) of 223 participants experienced late miscarriage or PTB.

Both groups had similar rates of gestational diabetes (25% in the metformin group vs 24% in the placebo group), preeclampsia and hypertension. Women randomized to metformin did gain less weight during pregnancy (8.7 vs 11.5 kg, P < 0.0001, CI: -4.1 to -1.5). The authors noted that this was significant as the study participants had an average body mass index of 29 kg/m2, which would be considered overweight. There was no significant difference in birth weight or length either. However, offspring exposed to metformin had larger head circumference compared to placebo (35.4 vs 34.7 cm, P = 0.03, CI: 0.07 to 1.2).

While the results from the study illustrate that there are benefits to taking metformin for women with PCOS, the researchers note that more data are needed. They expressed surprise and concern that metformin did not have a significant effect on the rate of gestational diabetes. More research is needed to explore why the glucose-lowering effect of metformin was not seen among those patients.