Is there a lack of CVD benefit with hormone therapy? Plus The Endocrine Society's Expo

March 18, 2015

A Cochrane meta-analysis examines if there is any cardiovascular disease prevention benefit from postmenopausal hormone therapy. Plus from The Endocrine Society's 97th Annual Expo, the benefits of abaloparatide in treating osteoporosis and the impact of smoking while pregnant on the diabetes risk of female children.

A meta-analysis of 19 trials involving more than 40,000 women found strong evidence that postmenopausal hormone therapy (HT) has little if any benefit in primary or secondary prevention of cardiovascular disease (CVD). The authors of the report, published by the Cochrane Heart Group, caution that the findings “need to be carefully considered” and that “the same treatment offers benefits in some women, but harms in others.”

The goal of the meta-analysis was to assess whether HT afforded prevention of CVD in postmenopausal women and whether those affects differed for primary versus secondary prevention. Included in the analysis were randomized controlled comparisons of oral HT versus placebo or a no-treatment control with administration for a minimum of 6 months (range 7 months to 10.1 years). Most of the studies were performed in the United States and the mean age of participants was 60 years.

The authors noted that study quality overall was good, with low risk of bias and that findings from the three largest trials dominated. Evidence was high quality indicating that HT had no protective effects for either primary or secondary prevention of all-cause mortality, cardiovascular death, non-fatal myocardial infarction, angina, or revascularization. In the HT arm, however, risk of stroke was increased for combined primary and secondary prevention (RR 1.24, 95% CI 1.10-1.41). In comparison with placebo, HT also increased risk of risk of venous thromboembolism (VTE) (RR 1.92, 95% CI 1.36-2.69) and pulmonary emboli (RR 1.81, 95% CI 1.32-2.48).

Using a subgroup analysis, the authors also looked at the impact of when treatment was started in relation to menopause. Rates of mortality (RR 0.70, 95% CI 0.52-0.95) and coronary heart disease (CH) (RR 0.52, 95% CI 0.29-0.96) were lower in the women who started HT less than 10 years after menopause. However, they remained at increased risk of VTE (RR 1.75, 95% CI 1.11-2.73). Starting HT more than 10 years after menopause had little effect on death or CHD but risks of stroke (RR 1.21, 95% CI 1.06-1.38) and VTE (RR 1.96, 95% CI 1.37-2.80) were increased.  

NEXT: Prenatal tobacco exposure and diabetes risk in offspring

 

Prenatal tobacco exposure linked to diabetes risk in female offspring

Women whose mothers smoked during pregnancy may be at increased risk of developing diabetes in adulthood, according to a poster presented at The Endocrine Society’s 97th Annual Meeting & Expo. While additional studies are required to confirm the results, the research suggests caution in smoking by or near pregnant women.

The prospective study looked at 1801 women aged 44 to 54 years who had been born in the Child Health and Development Studies pregnancy cohort between 1959 and 1967. Their mothers reported parental smoking in an early pregnancy interview, were members of the Kaiser Foundation Health Plan, and resided in the Oakland, California area. Diagnoses of diabetes mellitus were self-reported to physicians and the women provided blood for hemoglobin A1C measurement.

The researchers found that prenatal maternal smoking had a stronger effect on the daughters’ risk of diabetes than prenatal paternal smoking. This effect persisted after adjusting for parental race, diabetes, and employment (adjusted rate ratio [aRR] = 2.4 [95% confidence 1.4 - 4.1] P< 0.01 and aRR = 1.7 [95% confidence 1.0 – 3.0] p = 0.05, respectively]). Even after additional adjustment for the birth weight of the women and their current body mass index, the estimate of the effect of parental smoking remained unchanged.

Reported maternal smoking was found to be a significant predictor of a self-reported type 2 diabetes diagnosis (2.3 [95% confidence 1.0 - 5.0] P< 0.05). The women with parents who smoked had an increased risk of diabetes mellitus, independent of known risk factors.

Investigators concluded that exposure to smoking can contribute to the risk of diabetes mellitus, even in the absence of risk factors. 

NEXT: Efficacy of abaloparatide in treating osteoporosis

 

Multinational trial shows potential of abaloparatide in postmenopausal osteoporosis

Abaloparatide, an investigational osteoanabolic PTHrP analog, may be an effective treatment for postmenopausal osteoporosis, according to results of a Phase III trial presented at The Endocrine Society’s 97th Annual Meeting & Expo.

In the multinational ACTIVE double-blind, placebo-controlled fracture prevention trial, 1901 women received either 80 mcg of subcutaneous (SQ) abaloparatide, 20 mcg of SQ teriparatide, or placebo daily for 18 months. All of the women also took calcium and vitamin D supplements.

The groups were well-matched according to baseline demographics: the mean age was 68.8 years old and the mean body mass index was 25.1. Among the women, 16.3% had a history of 1 vertebral fracture, 28.2% had a history of 2 or more vertebral fractures, and 46.8% had at least one previous non-vertebral fracture. The mean baseline T-scores for the spine, femoral neck, and hip were -2.90, -2.14, and -1.90, respectively.

Among the 2118 women originally randomized who had baseline and post-therapy x-rays, the fracture rate (FR) associated with abaloparatide was 0.58% (n=690), representing a reduction in new incident vertebral FR of 86%, compared to the placebo group (n=711, FR 4.22%; [P<0.0001]). In the teriparatide group (n = 717), the FR of 0.84% was reduced by 80% (P<0.0001 vs placebo). Abaloparatide reduced non-vertebral fracture (Kaplan-Meier estimated [KM FR=2.7%, hazard ratio=0.57, P=0.0489) and clinical fracture (KM FR=3.9%, hazard ratio=0.55, P=0.0112) in comparison to placebo (KM non-vertebral FR=4.7%, KM clinical FR=8.3%). No statistically significant difference was seen between teriparatide and placebo for non-vertebral fracture (KM FR=3.3%, hazard ratio=0.72, P=0.2157) or clinical fracture (KM FR=4.8%, hazard ratio=0.71, P=0.1127).

Neither abaloparatide (n=824, KM FR 0.5%) nor teriparatide (n=818, KM FR 2.0%) significantly reduced wrist fractures when compared with placebo (n=821, KM FR 1.5%). However, the wrist FR was significantly lower in the abaloparatide group than in the teriparatide group (P = 0.0149). When compared with the placebo group, both abaloparatide and teriparatide were associated with increased bone mineral density (BMD) at the spine, femoral neck, and hip at 6, 12, and 18 months (P<0.0001 for all comparisons). Abaloparatide was better at increasing BMD.

Abaloparatide was considered well-tolerated in the study group and the most common reported adverse events were back pain, arthralgia, upper respiratory tract infection, hypercalciuria, and dizziness.

Given the reduction in incidence and risk of vertebral, non-vertebral, and clinical fractures in those who received abaloparatide, the researchers concluded that the drug may be a safe and effective treatment for osteoporosis in postmenopausal women.