A capsule containing a combination of 17-beta-estradiol and progesterone significantly improved vasomotor symptoms in menopausal women without causing a single case of endometrial hyperplasia.
The results of the 12-week REPLENISH study suggested that this preparation effectively treats vasomotor symptoms and could be a safe alternative to the popular, but unstudied, compounded bioidentical hormones that millions of women turned to after thecast doubt on the safety of hormone therapy, , and his colleagues in Obstetrics and Gynecology.
“17-beta-estradiol–progesterone may represent a new option, using natural hormones, for postmenopausal women, including the estimated millions currently using inadequately studied, non–FDA approved, compounded [hormone therapy],” wrote Dr. Lobo of Columbia University, New York.
randomized 1,845 postmenopausal women (mean age 55 years) to placebo or one of four active, daily, oral estradiol-progesterone doses (1 mg/100 mg, 0.5 mg/100 mg, 0.5 mg/50 mg, or 0.25 mg/50 mg). The primary safety outcome was endometrial hyperplasia. There were two primary efficacy endpoints: mean changes in frequency and severity of moderate to severe vasomotor symptoms from baseline at weeks 4 and 12.
There were no cases of endometrial hyperplasia with any estradiol-progesterone dose, nor were there any endometrial cancers. The rates of endometrial proliferation and endometrial polyps were low (about 3% each).
The frequency of vasomotor symptoms decreased significantly, compared with placebo, in all active groups. The severity of vasomotor symptoms also decreased significantly and in a dose-dependent manner. Onset of action was similarly dose-dependent, with the 1 mg/100 mg group experiencing a clinically meaningful benefit by week 3 and the 0.5 mg/50 mg group by week 6.
Adverse events were mild-moderate and included breast tenderness, headache, nausea, pelvic pain, vaginal bleeding, and vaginal discharge. Serious adverse events included acute pancreatitis, deep vein thrombosis (in a woman with prior left femoral popliteal bypass surgery and a family history of deep vein thrombosis), chronic obstructive pulmonary disease, infective cholecystitis, and breast cancer.
TherapeuticsMD sponsored the study; Dr. Lobo has received research grants from TherapeuticsMD and has served as a consultant for the company and several others. Some coauthors report additional research support from and consulting with TherapeuticsMD and other companies, and three coauthors are stock-holding employees of TherapeuticsMD.
SOURCE: Lobo RA et al. .