Safety and feasibility of estrogen receptor-β targeted phytoSERM formulation for menopausal symptoms: phase 1b/2a randomized clinical trial

Abstract

Objective: PhytoSERM is a formulation of genistein, daidzein, and S-equol that has an 83-fold selective affinity for estrogen receptor-β (ERβ); and may enhance neuron function and estrogenic mechanisms in the brain without having peripheral estrogenic activity.

Methods: We conducted an overarching, two-stage, dose-ranging, double-blinded, randomized, placebo-controlled trial of 12 weeks duration comparing 50 and 100 mg/d of phytoSERM with placebo for noncognitively impaired, perimenopausal women aged 45 to 60, with intact uteri and ovaries, with at least one cognitive complaint, and one vasomotor-related symptom. Primary objectives were to assess safety and tolerability of a 50 and 100 mg daily dose; and, secondly, to evaluate potential indicators of efficacy on cognition and vasomotor symptoms over 4 and 12 weeks, and using an embedded, 4-week, 2-period, placebo-controlled crossover trial for a subset of participants.

Results: Seventy-one women were randomized to treatment; 70 were evaluated at 4 weeks; 12 were entered into the crossover study; 5 did not complete 12 weeks. Reasons for discontinuation were withdrawal of consent (n = 1) and lost to follow-up (n = 4). Adverse events occurred in 16.7% (n = 4) placebo, 39.1% (n = 9) 50 mg/d, and 29.2% (n = 7) 100 mg/d treated participants; 85% were mild and none was severe. Vaginal bleeding occurred in 0, placebo; 1, 50 mg; and 3, 100 mg/d participants.

Conclusions: The phytoSERM formulation was well tolerated at 50 and 100 mg daily doses. Based on safety outcomes, vaginal bleeding at the 100 mg dose, and vasomotor symptoms and cognitive outcomes at 12 weeks, a daily dose of 50 mg was considered preferable for a phase 2 efficacy trial.

Trial registration: ClinicalTrials.gov NCT01723917.

Conflict of interest statement

Conflicts of interest/ financial disclosures: LSS, GH, AAF, Y-LC, SP, and WJM have no disclosures relevant to this work. RDB and LZ hold US Patents 8552057 and 8680140 on phytoSERM formulation.

Figures

Figure 1.

CONSORT flow diagram

Figure 2.

Parallel-group treatment comparisons: Change from baseline on vasomotor and neuropsychological composites, at 4 weeks (A) and 12 weeks (B)

Figure 2.

Parallel-group treatment comparisons: Change from baseline on vasomotor and neuropsychological composites, at 4 weeks (A) and 12 weeks (B)