ORLANDO, Fla. — An investigational combination of 17beta-estradiol and progesterone appears to be safe and effective for reducing hot flash frequency and severity in menopausal women, according to results of the REPLENISH trial reported here.
Researchers observed “good efficacy of a combined ‘natural,’ ‘native’ or ‘bioidentical’ estrogen and progesterone combination pill at several doses for the treatment of hot flushes,” presenter Rogerio Lobo, MD, professor of obstetrics and gynecology at Columbia University, told Endocrine Today.
Use of compounded bioidentical hormone therapy is extremely prevalent in the United States, and the softgel capsule identified as TX-001HR (TherapeuticsMD) could be the first bioidentical hormone product to be FDA approved, Lobo said.
“Depending on the audience, I think most people assume that ‘bioidentical’ compounded formulations are approved for use and have been studied extensively,” Lobo said. “This is not the case.”
In the phase 3 randomized, double blind, placebo-controlled REPLENISH trial (NCT01942668), researchers evaluated the safety and efficacy of four doses of estradiol/progesterone against placebo in 1,835 postmenopausal women aged 40 to 65 years with an intact uterus and vasomotor symptoms: 1 mg/100 mg (n = 415), 0.5 mg/100 mg (n = 424), 0.5 mg/50 mg (n = 421), 0.25 mg/50 mg (n = 424), placebo (n = 151). The safety study evaluated women who received at least one treatment dose with an acceptable endometrial biopsy at baseline and at day 326 with no major protocol violations.
No cases of endometrial hyperplasia or endometrial cancer were observed among any of the groups. Consensus reads of active and disordered hyperplasia at 12 months were identified in 2.9% of the 1 mg/100 mg group, 1.7% of the 0.5 mg/100 mg group, 0.3% of the 5 mg/50 mg group, 1.1% of the 0.25 mg/50 mg group, and none of the placebo group.
In an effectiveness substudy, researchers evaluated self-reported hot flash frequency and severity in 599 of the women (mean age 54.6 years; mean BMI 26.6 kg/m2; 67% white). All women kept hot flash diaries leading up to baseline and reported at least 7 events per day or at least 50 events per week.
Compared with the placebo group, women in the 1 mg/100 mg and 0.5 mg/100 mg groups reported statistically significant reductions from baseline in hot flash frequency and severity at weeks 4 (all, P< 0.05) and 12 (all, P < .001); those in the 0.5 mg/50 mg group reported reductions in frequency and severity at week 12 (P < .05), and those in the 0.25 mg/50 mg reported reduced frequency at weeks 4 and 12 (P .001).
Archer DF, et al. LB SUN 07.
Lobo R, et al. OR16-4. Presented at: The Endocrine Society Annual Meeting; April 1-4, 2017; Orlando, Fla.
Disclosures: Archer and Lobo reports various financial ties with various pharmaceutical companies.