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The effects of postmenopausal hormone therapy on serum estrogen, progesterone, and sex hormone-binding globulin levels in healthy postmenopausal women

Edlefsen, Kerstin L. MD1; Jackson, Rebecca D. MD2; Prentice, Ross L. PhD3; Janssen, Imke PhD4; Rajkovic, Aleksandar MD, PhD5; O'Sullivan, Mary Jo MD6; Anderson, Garnet PhD3

doi: 10.1097/gme.0b013e3181cb49e9

Objective: Differences in disease outcomes between users and nonusers of hormone therapy (HT) and between users of estrogen therapy (ET) and users of estrogen + progesterone therapy (EPT) may relate to differences in serum hormone concentrations between these populations. In this study, we examined the response of serum hormone levels in healthy postmenopausal women after 1 year of HT.

Methods: A representative subsample of 200 healthy adherent participants from the active and placebo groups of the Women's Health Initiative randomized controlled clinical trials of ET (conjugated equine estrogens 0.625 mg daily) or EPT (ET plus medroxyprogesterone acetate 2.5 mg daily) were selected for the determination of selected sex hormone levels at baseline and 1 year after randomization.

Results: In participants receiving active ET intervention compared with placebo, estrogenic hormone levels increased from baseline to year 1 by 3.6-fold for total estrone, 2.7-fold for total estradiol, and 1.8-fold for bioavailable and free estradiol concentrations. Serum sex hormone-binding globulin concentrations also increased 2.5-fold. In contrast, progesterone levels decreased slightly in women taking exogenous EPT. The response of serum estrogens and sex hormone-binding globulin did not differ substantially with the addition of progesterone. In subgroup analyses, hormone response varied by age, ethnicity, body mass index, smoking status, vasomotor symptoms, and baseline hormone levels.

Conclusions: These data provide a reference point for the serum hormone response to HT and demonstrate that the response of serum estrogens is similar for ET and EPT. The implications of the slight decrease in serum progesterone levels with EPT therapy are uncertain. Potential treatment interactions for estrogenic hormones were identified, which suggest a larger response to HT in women with low endogenous levels.

Conjugated equine estrogens and combined hormone therapy significantly increased circulating levels of total, free, and bioavailable estradiol; estrone; and sex hormone-binding globulin by twofold to fourfold over placebo after 1 year.

From the 1Department of Laboratory Medicine, University of Washington Medical Center, Seattle, WA; 2Division of Endocrinology, Diabetes and Metabolism, The Ohio State University, Columbus, OH; 3Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA; 4Department of Preventive Medicine, Rush University Medical Center, Chicago, IL; 5Magee Women's Research Institute, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA; and 6Department of Obstetrics and Gynecology, University of Miami Miller School of Medicine, Miami, FL.

Received September 10, 2009; revised and accepted November 16, 2009.

Funding/support: The Women's Health Initiative program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, and US Department of Health and Human Services, through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221.

Financial disclosure/conflicts of interest: None reported.

Address correspondence to: Kerstin L. Edlefsen, MD, Department of Laboratory Medicine, University of Washington, Seattle Cancer Care Alliance Mail Stop G7-800, 825 Eastlake Ave. E., Seattle, WA 98109. E-mail:

©2010The North American Menopause Society