UPDATE:
Once viewed as a virtual panacea for the various ills associated with aging in women, hormone replacement therapy (HRT) has surprisingly and precipitously fallen from grace, largely as a result of the findings of the Womens' Health Initiative released in July, 2002. Not only did the active treatment, Prempro, a combination of estrogen and progestin, fail to prevent heart attacks and strokes as had been expected based on decades' worth of observational studies, but it actually increased the incidence of both as well as of blood clots. There was also an increase in invasive breast cancer, though this was not as surprising since there had always been conflicting data on the role of hormones in breast cancer. Specifically for every 10,000 women there were seven more occurences of coronary disease, eight more strokes, eight more pulmonary emboli (blood clots) and eight more invasive breast cancers. Although there were also six fewer colorectal cancers and five fewer hip fractures, overall the benefits did not outweigh the risks, leading the researchers to halt the combination therapy (i.e estrogen and progestin) arm of the study early.
Further, it is important to note that the hormones used in the study, conjugated equine estrogens, are derived from the urine of pregnant mares and the above cited results may not be generalizable to other forms of estrogen.
Many physicians and experts are nevertheless suggesting that short-term use of HRT may still be safe for the treatment of hot flashes and other troublesome symptoms of menopause for which estrogen is the only proven effective remedy. However, given the fact that the earlier HERS study found an increased incidence of coronary events in women with known cardiovascular disease within the first two years of that study, a risk that appeared to level off by the fourth year, even short-term use, generally defined as less than five years, does appear to carry some risk. While the HERS study was conducted using women with documented heart disease, other studies have shown that there is a high incidence of occult heart disease, particularly in women. Thus, even short-term use of combination estrogen-progestin therapy may not necessarily be risk-free, leaving women to search for alternative treatments for hot flashes, night sweats and the other discomforts of menopause.
The estrogen alone arm of the study has also been discontinued. While no incresed risk of either breast cancer or heart disease, there was a slight increase in stroke risk in women taking estrogen
to be continued . . .
(currently researching some of the alternative treatments so please keep checking back if you're interested in additional info)
Meanwhile, here are some books available from Amazon.com:
Freakonomics : A Rogue Economist Explores the Hidden Side of Everything
Blink : The Power of Thinking Without Thinking
With apologies for the delay, I hope to update this site soon to include the new, much-publicized and somewhat surprising findings of the Women's Health Initiative Study. These findings are, however, consistent with last year's (July, 2001) guidelines from the American Heart Association that HRT no longer be prescribed to prevent heart attacks and strokes, a recommendation based on a growing body of evidence that hormone supplements may actually be harmful. Meanwhile, I will leave this up as an historical curiosity if nothing else, though the section on the HERS study remains relevant.
WELCOME TO MY DETERMINEDLY LOW-TECH WEB SITE
YESTERDAY'S NEWS
Menopause is often associated with weight gain, a side-effect unfortunately also commonly, though perhaps incorrectly, believed to be associated with the hormones, usually either some form of estrogen (estrogen replacement therapy or ERT) or an estrogen-progesterone combination (hormone replacement therapy or HRT) often prescribed to alleviate symptoms such as hot flashes, night sweats, vaginal dryness, irritability, mood changes and changes in sleeping patterns, including insomnia.
The pros and cons of hormone replacement therapy are generally well-known: decreased risk of both cardiovascular disease and osteoporosis vs. a potential increased risk of breast cancer, although this remains controversial. Other potential risks associated with HRT/ERT include an increased incidence of venous thrombosis (blood clots), an exacerbation of pre-existing liver disease, and for women with an intact uterus taking estrogen alone, an increased risk of endometrial cancer. Some users can also develop hypertension.
Preliminary evidence suggests that ERT/HRT users appear to be less susceptible to Alzheimer's Disease. Some studies have also observed a decreased incidence of colon cancer among women taking supplemental hormones. Dr. A. Paganini-Hill found a 35% lower risk of colorectal cancer in ERT users. According to the American Cancer Society, estrogen replacement for only a year resulted in less deaths from colon cancer, the third leading cause of cancer deaths among women.
In addition to these potential advantages and disadvantages associated with use of supplemental estrogen and/or progesterone, WEIGHT GAIN is also a concern. For reasons which are still unclear, WEIGHT GAIN TENDS TO OCCUR IN WOMEN DURING AND AFTER MENOPAUSE, WHETHER OR NOT THEY CHOOSE HORMONE REPLACEMENT THERAPY. According to the Postmenopausal Estrogen and Progestin Intervention (PEPI) Trial, the women on placebo experienced a much larger weight gain than those receiving supplemental hormones, who did, however, also experience 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 oral conjugated equine estrogen (CEE), 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 medroxyprogesterone acetate and 2.0 lbs. with MPA administered continuously. Those assigned to 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 (the luteal phase) if ovulation has occurred. Progesterone, often considered the most fattening of the steroid hormones, 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.
Estrogen can also stimulate the growth of fibroids, benign tumors of the uterus which are very common is peri and post-menopausal women. An increase in the size of previously undiagnosed fibroids may result in a small increase in weight or girth. Fibroids are often undiagnosed since they can be symptomless. Diagnosis can be easily, non-invasively and painlessly made via pelvic ultrasound. ERT/HRT is generally contra-indicated in women with fibroids.
The results of an earlier trial are consistent with those of the PEPI trial. According to a long-term 15 year study reported in the Journal of the American Medical Association, Kritz-Silverstein and Barret-Connor concluded that hormone replacement therapy did not result in either the weight gain or the central obesity ( fat around the middle) often seen in postmenopausal women. The hormone users had taken hormones either continuously or intermittently (JAMA, 1996; 275: 46-49) for 15 years.
While the authors of the above study, known as the Rancho Bernardo Study, conclude that HRT did not result in weight gain, this conclusion does not appear to be warranted, given the fact that the women who used hormones were leaner to begin with. Since there was no difference in the weight of the groups at the end-point of the trial, the study in fact suggests that the hormone users must have indeed gained more weight during the study period.
While admittedly not scientific, perhaps the most convincing evidence that estrogen replacement therapy does not cause weight gain is the fact that estrogen, specifically Premarin, remains among the best-selling drugs year after year, though it has recently been deposed from its top 1 or 2 spot by the arthritis drug Celebrex, the ulcer drug Prilosec, and the blockbuster Viagra. Since slenderness is rightly or wrongly considered arguably the most important element of attractiveness, women would simply NOT keep on taking a drug that causes serious weight gain, regardless of its other benefits.
The specific cause of the weight gain and central obesity ("middle-aged spread") observed in post-menopausal women who do not use hormones is not yet clear but is believed to be due to the loss of muscle mass and consequent slowing of the metabolism that occurs in both men and women during middle age. Estrogen replacement therapy has been shown to reduce the accumulation of fat around the waist, a type of obesity considered to be more dangerous than the accumulation of fat in the hips and thighs, the so-called "pear-shaped" obesity. The central "apple-shaped" obesity is more often associated with diabetes and hypertension and elevated cholesterol and blood fat levels, all risk factors for cardiovascular disease.
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 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 and more than can be explained by an increased appetite. The exact mechanism underlying this remains unclear, as does the mechanism underlying menopausal weight gain.
According to anecdotal reports, some women using a transdermal estrogen patch note an intense hunger, particularly a craving for sweets, whenever it's time for a new patch.
Unfortunately, the usual remedy for weight gain as well as for many other ills, a low-fat diet, may be somewhat counterproductive. Low fat diets often reduce cholesterol and cholesterol is the precursor for all steroid hormones, including estrogen. If it is the lack of estrogen that contributes to weight gain and the central redistribution of fat, and this is only speculation at this point with mo conclusive evidence, then a low-fat diet would not necessarily result in weight loss. In other words, do not abandon your low-fat diet.
It would be interesting to investigate the effect of a low-fat diet on hot flashes, a known symptom of estrogen deficiency. However this would be a difficult study to conduct in a free-living population as it would be difficult to control for the fact a woman would obviously be aware that she was eating a low-fat diet and this awareness could conceivably affect the number or intensity of the hot flashes she may or may not experience. It would also be interesting to study if administering cholesterol-lowering drugs such as the statins (Zocor, Pravachol, Lipitor et al) affects the frequency of hot flashes.
Although it is commonly believed that ERT/HRT causes weight gain, in general scientific studies due not support this. The PEPI trial is significant because it was a randomized, placebo-controlled trial, meaning that subjects were randomly assigned to one of several groups (placebo, estrogen alone, estrogen with a progestin added for 12 days, or estrogen with progestin continuously, ) .
Other major studies, notably the famed Nurses' Health Study, the source of much of the important information on the effects of hormone replacement therapy, were not randomized. Participants who had elected to take hormones or not were observed for changes in their health status over a period of years. However, because the women decided on their own whether or not to use HRT, it is not possible to rule out confounding factors, such as the the characteristics of the women who choose to take hormones.
For example, because leaner, better-educated, more affluent women tend to use HRT, the decrease in cardiovascular disease often attributed to estrogen cannot be conclusively attributed to estrogen but may in fact be due to the other factors. Is there less heart disease because the women were leaner to begin with, better-educated and therefore tended to eat a lower fat diet and exercise more, both of which are correlated with levels of education, or more affluent with better access to health care??
In terms of weight gain, did HRT users experience less weight gain because they tended to be leaner to begin with? The common and long-standing belief that estrogen and progesterone cause weight gain may in fact discourage overweight women from using HRT. Only more randomized studies can begin to answer these questions.
The ongoing Women's Health Initiative (WHI) sponsored by the National Institutes of Health (NIH) and scheduled to be completed in 2005, should also eventually provide some data, although initially there had been some difficulty recruiting subjects, with many women unwilling to enroll in a study where they would be randomly and blindly (i.e. neither the researchers nor the subjects would know what they were taking) assigned to either hormone therapy or to a placebo, since the issue of whether or not to use HRT/ERT has become somewhat polarized with adherents firmly convinced of the benefits and opponents equally fervently convinced of the risks.
This problem has plagued several other studies, with the New York Times reporting the difficilties encountered in a search for subjects in a study of the effect of estrogen on Alzheimer's Disease after several studies had noted a beneficial effect: women were unwilling to risk being assigned to the placebo group.
The issue has also become somewhat politicized with some people feeling that replacing hormones no longer produced may delay or stave off some of the diseases and changes associated with aging, while others feel that menopause is a natural event and should not be treated as a hormone deficiency disease and thus "medicalized," further complicating the decision.
While conceding that studies do appear to show cardiovascular benefits, many researchers neverthelesss feel that the long-term safety and efficacy of ERT/HRT has yet to be established. The cardiovascular benefits are believed to be a result of the more favorable cholesterol profile in ERT/HRT users, with a decrease in the atherogenic LDL cholesterol and an increase in HDL, the so-called "good" cholesterol, as well as of a direct effect of estrogen on blood vessels.
However, the somewhat surprising findings of the Heart and Estrogen/progestin Replacement Study (HERS) study (JAMA 1998; 280:605-613, 650-652), which found an increased risk of adverse cardiovascular events in women with heart disease on hormone replacement therapy in the first years of HRT, appear to validate this concern. It should be emphasized that these findings are preliminary and need to be replicated by additional studies.
Further, the study participants already had heart disease and the results may therefore not be generalizable to healthy women concerned with the prevention of cardiovascular disease. The initially increased risk appeared to level off and actually decreased in the final 2 years of this 4 year study. Additionally, 96% of the subjects were between 55-80 years old and years since the onset of menopause may have been a factor. It is also important to note that estrogen alone was NOT tested. Progesterone/progestins have often been believed to negate the cardioprotective effects of estrogen.
It is also possible that the increased blood volume resulting from the sodium-retaining effects of estrogen and/or progestin created an increased workload on hearts already damaged or weakened by disease, thereby worsening the disease and causing symptoms. This is consistent with the fact that the increased risk levelled of and actually decreased during the final 2 years of the study.
However, the American College of Cardiology (ACC) and the American Heart Association (AHA) now recommend against starting HRT for women who have had a heart attack, although women who have been taking HRT prior to a heart attack may continue.
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LAST UPDATED:July 29, 2004
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