Reduced-calorie dietary weight loss, exercise, and sex hormones in postmenopausal women: randomized controlled trial

Abstract

Purpose: Estrogens and androgens are elevated in obesity and associated with increased postmenopausal breast cancer risk, but the effect of weight loss on these biomarkers is unknown. We evaluated the individual and combined effects of a reduced-calorie weight loss diet and exercise on serum sex hormones in overweight and obese postmenopausal women.

Patients and methods: We conducted a single-blind, 12-month, randomized controlled trial from 2005 to 2009. Participants (age 50 to 75 years; body mass index > 25.0 kg/m(2), exercising < 100 minutes/wk) were randomly assigned using a computer-generated sequence to (1) reduced-calorie weight loss diet ("diet"; n = 118), (2) moderate- to vigorous-intensity aerobic exercise ("exercise"; n = 117), (3) combined reduced-calorie weight loss diet and moderate- to vigorous-intensity aerobic exercise ("diet + exercise"; n = 117), or (4) control (n = 87). Outcomes were estrone concentration (primary) and estradiol, free estradiol, total testosterone, free testosterone, androstenedione, and sex hormone-binding globulin (SHBG) concentrations (secondary).

Results: Mean age and body mass index were 58 years and 30.9 kg/m(2), respectively. Compared with controls, estrone decreased 9.6% (P = .001) with diet, 5.5% (P = .01) with exercise, and 11.1% (P < .001) with diet + exercise. Estradiol decreased 16.2% (P < .001) with diet, 4.9% (P = .10) with exercise, and 20.3% (P < .001) with diet + exercise. SHBG increased 22.4% (P < .001) with diet and 25.8% (P < .001) with diet + exercise. Free estradiol decreased 21.4% (P < .001) with diet and 26.0% (P < .001) with diet + exercise. Free testosterone decreased 10.0% (P < .001) with diet and 15.6% (P < .001) with diet + exercise. Greater weight loss produced stronger effects on estrogens and SHBG.

Conclusion: Weight loss significantly lowered serum estrogens and free testosterone, supporting weight loss for risk reduction through lowering exposure to breast cancer biomarkers.

Fig 1.

CONSORT diagram: Flow of participants through the Nutrition and Exercise for Women Trial. DEXA, dual x-ray absorptiometry; FSH, follicle-stimulating hormone; HRT, hormone-replacement therapy; SHBG, sex hormone–binding globulin.

Fig 2.

Change in hormone levels by weight loss category. (A) Estrone; (B) estradiol; (C) total testosterone; (D) sex hormone–binding globulin; (E) free estradiol; (F) free testosterone. (*) Testing for a trend in change from baseline to 12 months in hormones from controls through weight loss < 5% and ≥ 5% (for exercise only). For exercise: n = 80 for control, n = 72 for weight loss < 5%, n = 27 for weight loss ≥ 5%. (†) Testing for a trend in change from baseline to 12 months in hormones from controls through weight loss ≥ 10%. For diet: n = 80 for control, n = 28 for weight loss < 5%, n = 27 for weight loss 5% to 10%, n = 46 for weight loss ≥ 10%. For diet + exercise: n = 80 for control, n = 18 for weight loss < 5%; n = 21 for weight loss 5% to 10%; n = 69 for weight loss ≥ 10%. Statistical significance P value < .05.