The problem of weight gain

Schiff: We started by asking why women stop taking replacement hormones, despite such obviously beneficial effects as control of hot flushes and reversal of vaginal atrophy. We’ve talked about the two primary reasons for discontinuance: fear of breast cancer and breakthrough bleeding. A third reason why women refuse or discontinue HRT is their serious concern about weight gain. This is a matter that some women are reluctant to mention to their physicians. Dr. Berga, what’s your experience with this issue?

Berga: Weight gain is a very important topic. I bring it up with almost all patients considering HRT because I know how critical it is. And the thinner they are, the more critical it seems to be to them.

The best data on that subject are the data from the PEPI trial.³⁴ This was a randomized prospective study of 875 women with three combined therapy arms, an estrogen-alone arm, and a placebo arm. Nearly all the women gained weight during the 3 years of the study, but the women in the placebo arm gained the most weight. Weight gain was less—and about the same—in all three hormone arms. That’s interesting, because progestins can cause water retention and bloating, yet the women in the combined therapy groups had less weight gain than the placebo women and no more than the women receiving estrogen alone.

Nachtigall: We saw the same thing in the 10-year osteoporosis study we published in 1979.³⁵ The women were on placebo or high doses of estrogen with cyclic progestin. They had very similar diets, since they were all in a nursing home. At the end of the 10 years, with food from a city hospital, almost all the women had gained weight, but there was much less weight gain in the hormone replacement group. I was as surprised as anyone to see that result.

Schiff: It’s every clinician’s experience that if women are taking HRT, they’re going to blame any weight gain on hormones. When you ask them why they discontinued, they’ll say, “I stopped those damned pills because I put on weight.” How do you deal with that?

Berga: If the patient has a fixed belief that hormones are to blame, I don’t know that you can deal with it. But I don’t find most patients that inflexible. Typically a woman will say, “I thought I was gaining weight because I was taking hormones.” Then I’ll say, “You stopped the hormones and what happened? Did you lose weight, stay the same, or gain more weight?” Usually, they’ll have gained, so I explain that all of us are genetically programmed to gain weight as we get older and that their weight gain had nothing to do with hormones.

I believe that’s a statement you can support with data. For example, one study that compared HRT with placebo for total body fat and abdominal fat found less abdominal fat in the HRT-treated women.³⁶

Schiff: So women on HRT are more likely to maintain their premenopausal gynecoid figure as opposed to taking on an android figure after menopause?

Berga: Yes. What we’re doing with hormones is influencing where the fat goes or somewhat increasing a woman’s metabolic rate so that she acquires a little less fat. In either case, it’s a benefit.

Sarrel: We also need to remember that changes in thyroid function affect weight in postmenopausal women. Because estrogens can induce an increase in thyroid-binding globulin, I evaluate thyroid function whenever a postmenopausal woman complains of excess weight gain.