Pharmacokinetics and safety profile of single-dose administration of an estrogen receptor β-selective phytoestrogenic (phytoSERM) formulation in perimenopausal and postmenopausal women

Menopause. 2018 Feb;25(2):191-196. doi: 10.1097/GME.0000000000000984.


Objective: Selected estrogen receptor β-selective phytoestrogen (phytoSERM), a preparation of genistein, daidzein, and S-equol, has an 83-fold selective affinity for estrogen receptor (ER) β, and may promote neuronal survival and estrogenic mechanisms in the brain without exerting feminizing activity in the periphery. The aim of this study was to assess the safety, tolerability, and single-dose pharmacokinetics of the phytoSERM formulation in perimenopausal and postmenopausal women.

Methods: Eighteen women aged 45 to 60 years from a 12-week clinical trial evaluating cognitive performance and vasomotor symptoms were randomly assigned to placebo, 50 mg, or 100 mg phytoSERM treatment groups. Plasma levels of the three parent phytoestrogens and their metabolites were measured before and at 2, 4, 6, 8, and 24 hours after ingestion by isotope dilution high-performance liquid chromatography (HPLC) electrospray ionization tandem mass spectrometry.

Results: Plasma concentrations of genistein, daidzein, and S-equol peaked at 9, 6, and 4 hours, respectively, for the 50-mg dose, and at 6, 6, and 5 hours, respectively, for the 100-mg dose. The maximum concentration (Cmax) and area under the curve (AUC) for the three parent compounds were greater in the 100-mg dose group, indicating a dose-dependent change in concentration with the phytoSERM treatment. No adverse events were elicited.

Conclusions: A single-dose oral administration of the phytoSERM formulation was well-tolerated and did not elicit any adverse events. It was rapidly absorbed, reached high plasma concentrations, and showed a linear dose-concentration response in its pharmacokinetics. These findings are consistent with previously reported parameters for each parent compound ( NCT01723917).

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Area Under Curve
  • Drug Combinations
  • Equol / blood
  • Equol / pharmacology*
  • Estrogen Receptor beta / agonists
  • Female
  • Genistein / blood
  • Genistein / pharmacology*
  • Humans
  • Isoflavones / blood
  • Isoflavones / pharmacology*
  • Middle Aged
  • Phytoestrogens / blood
  • Phytoestrogens / pharmacology*
  • Selective Estrogen Receptor Modulators / blood
  • Selective Estrogen Receptor Modulators / pharmacology*


  • Drug Combinations
  • Estrogen Receptor beta
  • Isoflavones
  • Phytoestrogens
  • Selective Estrogen Receptor Modulators
  • Equol
  • daidzein
  • Genistein

Associated data