Are serum estrogen concentrations associated with menopausal symptom bother among postmenopausal women? Baseline results from two MsFLASH clinical trials

Carolyn J. Crandall, Joseph C. Larson, Kristine E. Ensrud, Andrea Z. LaCroix, Katherine A. Guthrie, Susan D. Reed, Shalender Bhasin, Susan Diem

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Objectives: To evaluate whether single measurements of serum estradiol (E2), estrone (E1) and sex hormone-binding globulin (SHBG) concentration distinguishes between women with and without menopausal symptom bother. Study design: We analyzed baseline data from two clinical trials conducted in 2012–2017: MsFLASH 03 (178 peri-/post-menopausal women aged 40–62 years with bothersome vasomotor symptoms, mean age 54) and MsFLASH 05 (181 post-menopausal women aged 45–70 years with moderate-to-severe vulvovaginal symptoms, mean age 61). Main outcome measures: Symptom bother (hot flushes or flashes, night sweats, sweating, aching in muscles and joints, change in sexual desire, vaginal dryness during intercourse, and avoiding intimacy) in the past month was assessed using the Menopause-Specific Quality of Life questionnaire. Using logistic regression, we calculated the area under the receiver operating characteristic curve (AUC) values for E1, E2, and SHBG concentration in relation to being at least somewhat bothered (symptom bother score ≥3) by each symptom within each trial study population. Results: AUC values (95% confidence interval) ranged between 0.51 (0.41–0.60) and 0.62 (0.53, 0.72) for MsFLASH 03 and between 0.51 (0.42, 0.59) and 0.64 (0.53, 0.75) for MsFLASH 05. There was little evidence of associations between serum hormone levels and bother by a given menopausal symptom. Conclusion: These findings do not support the clinical utility of a single measurement of serum of E1, E2, or SHBG concentrations in differentiating between women who are bothered by a given menopausal symptom and those who are not.

Original languageEnglish (US)
Pages (from-to)23-30
Number of pages8
StatePublished - Aug 2022

Bibliographical note

Funding Information:
MsFLASH 03 was supported by a cooperative agreement issued by the National Institute on Aging (NIA), in collaboration with the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Center for Complementary and Alternative Medicine (NCCAM) and the Office of Research on Women's Health (ORWH), and NIA grants U01AG032659 , U01AG032669 , U01AG032682 , U01AG032699 , and U01AG032700 . MsFLASH 05 was supported by National Institutes of Health National Institute on Aging : 5R01AG048209 . The sponsor had no input into, or control over, the analysis of data, the writing of the manuscript, or the decision to submit the article for publication.

Publisher Copyright:
© 2022 The Author(s)


  • Dyspareunia
  • Estradiol
  • Estrone
  • Hot flashes
  • Hot flushes
  • Joint aches
  • Menopause
  • Vaginal dryness
  • Vasomotor symptoms


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