Does ospemifene increase vasomotor symptoms?

August 17, 2016

A study examines if ospemifene is linked to increased hot flashes. Plus: Do certain cerclage sutures increase the risk of preterm birth? Also, do pregnancy delays actually decrease the risk of microcephaly as a result of congenital Zika infection?

Postmenopausal women who use ospemifene, a selective estrogen receptor modulator, may experience an increase in vasomotor symptoms during their first 4 weeks on the drug, according to results of a pooled analysis of Phase II and Phase III randomized trials published in Menopause.

The researchers compiled the incidence of vasomotor symptoms treatment-emergent adverse events (TEAEs) from 5 randomized, placebo-controlled clinical studies and baseline parameters associated with vasomotor symptom incidence. Data from a previously unpublished, 6-week placebo-controlled study evaluating ospemifene’s effects on the frequency and severity of vasomotor syndromes were used as well.

An analysis of pooled vasomotor symptom TEAE data for 2166 women showed an 8.5% incidence of vasomotor symptoms for ospemifene and 3.2% for placebo (P < 0.0001). The first 4 weeks of ospemifene treatment saw the highest frequency of vasomotor symptoms and the frequency decreased thereafter. An increased incidence of hot flashes was more likely in women who had taken hormone therapy within 6 months before study start (P = 0.0234), had more vasomotor symptom days per month at baseline (P = 0.0313), and took the study treatment for a longer period of time (P = 0.0234), according to results of logistic regression analysis. In the unpublished study of 198 postmenopausal women who experienced moderate to severe vasomotor symptoms, ospemifene 60 mg/d did not worsen the severity and frequency of existing vasomotor symptoms.

The researchers concluded that vasomotor symptom TEAEs were more frequent with ospemifene 60 mg/d than with placebo, especially in women who had previously used hormone therapy. The vasomotor symptoms lessened at 4 weeks and ospemifene did not worsen existing vasomotor symptoms in women who were experiencing moderate to severe hot flashes.

NEXT: Cerclage suture linked with preterm birth

 

Cerclage suture linked with preterm birth

A study by British researchers suggests that cerclages done with braided sutures are more likely to end in preterm birth (PTB) or a nonviable pregnancy than are those done with monofilament sutures. The braided material, say the authors, appears to promote vaginal bacterial dysbiosis, which in turn results in local tissue inflammation and premature cervical remodeling.

Published in Science Translation Medicine, the findings are from a retrospective analysis and the researchers see an urgent need for clinical trials, powered for the outcomes of PTB, neonatal morbidity, and mortality, to assess the impact of cerclage suture material.

The authors assessed birth outcomes in a cohort of 678 women who received cervical cerclages at five UK university hospitals over a 10-year period. Half of the procedures were done with braided suture material and half with monofilament suture. The women in whom the braided suture was used had higher rates of nonviable births (delivery <24 weeks or intrauterine death) compared to those in whom the monofilament suture was used (15% versus 5%; P<0.0001). The braided suture also was associated with an increased rate of PTB at 24 to 37 weeks’ gestation: 28% versus 17% for monofilament; P<0.0001.

Although a history of PTB contributed significantly to the nonviable births, the researchers said the braided suture was the “primary driver” of that observed outcome irrespective of potential confounders including maternal age, ethnicity, and parity. It was also the major variable influencing risk of PTB, independent of maternal age, ethnicity, parity, and history of previous PTB. Distribution of cervical length was similar between the braided and monofilament suture groups.

The braided material, the authors found, caused a “marked shift toward dysbiosis” 4 weeks after cerclage and that change persisted until 16 weeks after the procedure. The material was also associated with an increasing proportion of women with reduced levels of Lactobacillus spp and increased diversity of anaerobic bacteria. In contrast, the women who had cerclages with monofilament suture maintained high levels of Lactobacillus spp, which remained stable. The researchers also noted that the braided material was associated with increased release of inflammatory cytokines-including interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor-α-into cervicovaginal fluid.

“We estimate that a global shift to monofilament suture use for cervical cerclage would prevent 170,000 PTBs [number needed to treat (NNT), 9.4; 95% confidence interval (CI), 5.9 to 22.6] and 172,000 fetal losses [NNT, 9.3; 95% CI, 6.6 t 16.0) per annum worldwide,” said the authors. 

NEXT: How delaying pregnancy can decrease risk of microcephaly from Zika virus

 

How delaying pregnancy can decrease risk of microcephaly from Zika virus

Strategic delays when planning pregnancy may help mitigate birth defects caused by the Zika virus, according to results of an epidemiologic study published in Annals of Internal Medicine.

Researchers used a vector-borne Zika virus transmission model fitted to the epidemiologic data derived from 2015 to 2016 in Colombia. The intervention was recommendations to delay pregnancy by 3, 6, 9, 12, or 24 months, at different levels of adherence. Weekly and cumulative incidence of prenatal infections and microcephaly cases were measured.

The authors found that with 50% adherence to the recommendations to delay pregnancy by 9 to 24 months, the cumulative incidence of prenatal Zika virus infection was likely to decrease by 17% to 44%, whereas recommendations to delay pregnancy by 6 months or less were likely to increase prenatal infections by 2% to 7%. Researchers noted that delaying pregnancy could lead to women becoming pregnant during the peak of a Zika virus outbreak.

It was noted that sexual transmission of Zika virus was not explicitly accounted for in the model due to limited data, but it would be implicit in the overall transmission rate.

The investigators concluded that delaying pregnancy can have a substantial effect on reducing cases of microencephaly but it can exacerbate Zika outbreaks if the duration of the delay is insufficient. Several factors need to be carefully considered when promoting strategic delays, including the timing of initiation of the intervention, duration of the delay, and population adherence. “In the absence of a vaccine or therapeutic drugs for Zika virus infection,” the authors said, “a combination of mass and individual pregnancy-delay strategies with effective vector-control measures is needed to curtail the spread and burden of the ongoing outbreak in the Americas.”