PMID- 30889096
OWN - NLM
STAT- MEDLINE
DCOM- 20200713
LR  - 20231013
IS  - 1530-0374 (Electronic)
IS  - 1072-3714 (Print)
IS  - 1072-3714 (Linking)
VI  - 26
IP  - 8
DP  - 2019 Aug
TI  - Safety and feasibility of estrogen receptor-beta targeted phytoSERM formulation for 
      menopausal symptoms: phase 1b/2a randomized clinical trial.
PG  - 874-884
LID - 10.1097/GME.0000000000001325 [doi]
AB  - OBJECTIVE: PhytoSERM is a formulation of genistein, daidzein, and S-equol that 
      has an 83-fold selective affinity for estrogen receptor-beta (ERbeta); 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.
FAU - Schneider, Lon S
AU  - Schneider LS
AD  - Keck School of Medicine of the University of Southern California, Los Angeles, 
      CA.
FAU - Hernandez, Gerson
AU  - Hernandez G
AD  - University of Arizona, Tucson, AZ.
FAU - Zhao, Liqin
AU  - Zhao L
AD  - School of Pharmacy, University of Kansas, Lawrence, KS.
FAU - Franke, Adrian A
AU  - Franke AA
AD  - University of Hawaii Cancer Center, Honolulu, HI.
FAU - Chen, Yu-Ling
AU  - Chen YL
AD  - Keck School of Medicine of the University of Southern California, Los Angeles, 
      CA.
FAU - Pawluczyk, Sonia
AU  - Pawluczyk S
AD  - Keck School of Medicine of the University of Southern California, Los Angeles, 
      CA.
FAU - Mack, Wendy J
AU  - Mack WJ
AD  - Keck School of Medicine of the University of Southern California, Los Angeles, 
      CA.
FAU - Brinton, Roberta D
AU  - Brinton RD
AD  - University of Arizona, Tucson, AZ.
LA  - eng
SI  - ClinicalTrials.gov/NCT01723917
GR  - P50 AG005142/AG/NIA NIH HHS/United States
GR  - R01 AG033288/AG/NIA NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Menopause
JT  - Menopause (New York, N.Y.)
JID - 9433353
RN  - 0 (Estrogen Receptor beta)
RN  - 0 (Isoflavones)
RN  - 531-95-3 (Equol)
RN  - 6287WC5J2L (daidzein)
RN  - DH2M523P0H (Genistein)
SB  - IM
MH  - Cognition/*drug effects
MH  - Cross-Over Studies
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Drug Therapy, Combination
MH  - Equol/*administration & dosage/pharmacokinetics
MH  - Estrogen Receptor beta/*drug effects/metabolism
MH  - Female
MH  - Genistein/*administration & dosage/pharmacokinetics
MH  - Hot Flashes/drug therapy
MH  - Humans
MH  - Isoflavones/*administration & dosage/pharmacokinetics
MH  - Middle Aged
MH  - Perimenopause/*drug effects
PMC - PMC6663614
MID - NIHMS1521413
COIS- 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.
EDAT- 2019/03/20 06:00
MHDA- 2020/07/14 06:00
PMCR- 2020/08/01
CRDT- 2019/03/20 06:00
PHST- 2019/03/20 06:00 [pubmed]
PHST- 2020/07/14 06:00 [medline]
PHST- 2019/03/20 06:00 [entrez]
PHST- 2020/08/01 00:00 [pmc-release]
AID - 10.1097/GME.0000000000001325 [doi]
PST - ppublish
SO  - Menopause. 2019 Aug;26(8):874-884. doi: 10.1097/GME.0000000000001325.