Provera (Medroxyprogestrone) and Weight Gain

These hormones are associated with aging and aging absolutely affects one’s weight. Metabolism slows, hormone levels change, and vigorous activity becomes more difficult. However, there is evidence that behavioral changes account for a greater proportion of weight gain than physiological changes.

As we grow older, we usually grow in wealth and free time…time to eat out, relax at home, or take vacations. Menopause also plays a role. One long-term, ongoing study of women before, during, and after menopause (the Rancho Bernardo Women’s Study) has shown that women tend to gain weight more rapidly during and after menopause.

To many people’s surprise, average weight gain is more rapid in those not taking hormones than in those taking hormones. But it bears repeating…weight gain tends to occur in women during and after menopause, whether or not they choose hormone replacement therapy (HRT).

According to the Postmenopausal Estrogen and Progestin Intervention (PEPI) Trial, women on placebo experienced a much larger weight gain than those receiving supplemental hormones, but even they experienced a small weight gain during the three years of the trial (J Clin Endocrinolog Metab. 1997; 82: 1549-1556). While the women on placebo gained an average of 4.6 lbs., the women taking estrogen alone gained 1.5 lbs. The estrogen administered was the type found in Premarin and Prempro. The women taking estrogen along with a progestin, either cyclically to approximate a natural cycle or continuously also gained weight–2.9 lbs. with cyclical Provera and 2.0 lbs. with a type taken daily. Those assigned to a micronized progesterone gained 2.9 lbs.

Medroxyprogesterone acetate (Provera) is the most common progestin prescribed in HRT. It is the progestin component of HRT that is most often associated with bloating and weight gain. Progestins are various synthetic versions of progesterone, the hormone secreted by the ovaries during the second half of the menstrual cycle if ovulation has occurred.

Progesterone, often considered a fattening steroid hormone, promotes fat synthesis and storage, as this would contribute to a successful pregnancy. Pregnancy requires a tremendous expenditure of energy (i.e. calories) and progesterone, whose name suggests its function (pro=for, gest=gestation), facilitates this in several ways. It increases appetite and slows down intestinal transit time, thus allowing more of the digested nutrients to be absorbed. It can also sometimes decrease insulin sensitivity (the action of insulin at the cellular level), resulting in a degree of insulin resistance which can elevate blood sugar. This conserves glucose for the fetus for growth and development, though at the expense of the mother. Progesterone can also result in the retention of sodium and water, which also contributes to weight gain. However in a non-pregnant state, the increased glucose resulting from the increased absorption of an increased amount of food is absorbed by fat cells causing weight gain. The levels of progesterone during pregnancy are, however, much higher than the levels normally found during the luteal phase of the menstrual cycle and are also higher than the progestins supplied in HRT.

Further, women with a uterus should not take estrogen without a progestin, since this increases the risk of endometrial cancer significantly. For those women who cannot tolerate progestins, an annual endometrial biopsy (usually an office procedure) is recommended if they choose to take estrogen. Whether or not such surveillance adequately prevents cancer has yet to be determined; further study is needed.

Estrogen can also promote sodium (salt) and water retention, increasing blood volume which is important in pregnancy since it increases delivery of nutrients etc. to the fetus. But in a non-pregnant state it can result in weight gain. The weight gain is often temporary since the body eventually adjusts to shifts in fluid. Haarbo and Associates reported that abdominal fat deposition is significantly lower in HRT users. Although all women in this Finnish study gained weight, the HRT users gained less weight and fat overall than non-users. Further, removal of the ovaries in mice, resulting in a lack of estrogen and progesterone similar to the hormonal situation in post-menopausal women, results in massive weight gain due, at least partially, to a greatly increased food intake. Administration of estradiol results in a return of food intake to normal levels and a consequent weight loss.

In women administration of GnRH agonists such as Lupron and other drugs which have the effect of shutting down the ovary are also notorious for causing weight gain, often a large amount (more than can be explained by an increased appetite). The exact mechanism underlying this remains unclear, as does the mechanism underlying menopausal weight gain.

In conclusion, it’s probably not the fault of the hormone replacement medication that most women gain weight through menopause. Having said that, we often see women whose weight gain was very closely associated with starting hormone therapy. Like most things, some women likely develop much more significant side effects than others do. It’s interesting to note that women in some countries tend to lose weight during and after menopause. This is very closely related to activity and diet changes. For instance, in Southeast Asia, women raising young children have more access to food and are less active than their older counterparts who return to work in the factories or fields.