Case 1

A 42-year-old G1 P1 is taking conjugated equine estrogens, 1.25 mg/day, for relief of hypoestrogenic symptoms. At age 35, she underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy for pelvic endometriosis. She now presents complaining of a 23-lb weight gain over the last 3 years. Her close friends tell her that “it’s the hormones” that have caused her to gain weight. The woman is employed as an administrative assistant and her exercise regimen consists of 30 minutes of brisk walking around her neighborhood three times per week. She eats out about six times per week. There is no family history for thyroid disorder, obesity, or adult-onset diabetes.

On physical examination, this woman is 5’4” tall and weighs 195 lb. Her blood pressure is 126/86 mm Hg, and her pulse is 78 per minute. General examination including pelvic examination is completely normal. Her deep tendon reflexes are 2/4. Laboratory values show a thyroid-stimulating hormone (TSH) of 4 µIU/mL (0.5–6 µIU/mL), hematocrit of 38, and a normal urinalysis.

Has estrogen therapy contributed to obesity in this woman?

Discussion
The incidence of obesity is increasing in the United States, due primarily to lifestyle changes related to a decrease in exercise, increase in sedentary activities, and higher caloric intake. Among adults in the US, if a body mass index > 27 kg/m² is considered obese, then over 50% of all adults in the US fit this criterion. It is clear that the basal metabolic rate decreases with increasing age, such that women as they approach the menopause experience gradual weight gain with aging.

In the evaluation of patients presenting with obesity, daily dietary intake, exercise, and other activities should be reviewed. The clinician should exclude a family history of metabolic disorders such as thyroid dysfunction, diabetes, and obesity.

Is there evidence that estrogen replacement therapy (ERT) plays a role in contributing to obesity in the menopausal woman? Evidence from the PEPI study, a randomized, controlled trial, shows no link between estrogen or estrogen-progestin use and weight gain. As shown in Figure 1, mean body weight increased in all women during the 3-year study.¹ More importantly, women receiving placebo experienced the greatest weight gain. In the absence of metabolic dysfunction, management of obesity should include a program of regular exercise, reduction in caloric intake with meal portion control, and peer support in a group or clinic setting. The use of crash or fad diets should be discouraged.

Figure 1 PEPI study: Post-treatment Measures Changes in body weight, waist/ hip ratio, and fibrinogen during 3 years of treatment with either placebo CEE 0.625 mg/day, CEE 0.625 mg/day with MPA 5 mg/day for 14 days, CEE 0.625 mg/day with MPA 2.5 mg/day, or CEE 0.625 mg/day with micronized progesterone (P4) 200 mg for 14 days. Source: The Writing Group for the PEPI Trial.1