Menopausal Options for Hormone Replacement Todd A. Hoover, MD, DHt Menopause is often thought of as an abnormal state.

In the past this disease was treated with hormone replacement therapy to keep you as normal as possible. But consider a womans life cycle. For the first decade or so, you produce very little hormones. Then puberty comes and brings fertility and the possibility of pregnancy. Then menopause comes and you return again to a state without hormones. The production of estrogen and progesterone at very high levels are linked to this special period of child-bearing years, while the majority of your life you have relatively low levels of these hormones. Instead of trying to maintain the normal state of fertility, late into life, perhaps the focus should be upon easing the transition back to a natural, non-fertile state. The common symptoms of menopause are clearly linked to the changes in estrogen and progesterone, but there are a series of reactions that occur throughout the body during these years. Control of hormone release is linked to the Hypothalamus section of the brain and the pituitary gland which releases hormones to stimulate the release of an egg from the ovary. This release, called ovulation, leads to the rise of progesterone in addition to the estrogen that is already being generated in the ovary. During menopause, release of eggs stops. The hormones produced in the pituitary rise dramatically in response. And the production of progesterone and estrogen begin to fluctuate and eventually fall off. Even though the ovaries stop producing high levels of estrogen, this hormone is still produced by fat tissue in the body. Likewise, progesterone is produced from the adrenal glands, but in a smaller amount than during the fertile period of life. Many physicians feel that there are several mechanisms at play during the transition of menopause that may be linked to symptoms. 1. Fluctuation of hormones from the pituitary gland (Follicle Stimulating Hormone FSH, and Luteinizing Hormone LH) 2. Rapid changes in estrogen and progesterone levels 3. Unbalanced relative amounts of estrogen and progesterone (typically lower amounts of progesterone) The main symptoms associated with menopause include: Hot flashes Memory Loss Insomnia Sweats Vaginal Dryness Changes in sex drive Irregular menstrual periods Heavy bleeding Concentration problems Hair loss Weight gain Mood changes

While replacing estrogen and progesterone in levels that approximate those that occur during the fertile period of life, there are some risks involved. The Womens Health Initiative study from 2002 looked at over 16,000 post-menopausal women for more than 5 years.i This large study showed clear evidence linking hormone replacement therapy was linked to more breast cancers and more severe types of cancer in the women who took both estrogen in the form of Premarin and a form of progesterone called Medroxyprogesterone. A similar study with more than 1 million women in Great Britain confirmed these findings and created even more concern.ii These reports led to a dramatic change in the use of hormone replacement therapy from being generally recommended to now being rarely used in most countries. Interestingly, further analysis of these studies showed that there may be some differences between those women who took both progesterone and estrogen compared to those women who took only estrogen. Typically, estrogen only use would only occur in women who have had a hysterectomy because of the risk to develop a cancer of the inside of the uterus with estrogen only treatment. The researches doing this analysis suggested that women who were taking only estrogen might actually be a lower risk for breast cancer.iii If you are considering hormone replacement therapy, you should consult your health care provider. Bio-identical hormones are sometimes recommended. Estrone (E1), Estradiol (E2), and Estriol (E3) are the three different types of estrogen that occur in the body. During your life these hormones are found in different amounts. During fertile years E2 predominates, while in menopause E1 which is produced in your belly fat is the major estrogen being made. E1 has been associated with a higher risk of certain types of estrogen sensitive breast cancers.iv Older research has shown that E3 may be associated with some protective effect against breast cancer.v Additional considerations for hormone replacement therapy include both the positive benefits and other negative risks associated with treatment. Known risks of treatment include higher frequency of blood clots, heart attacks and strokes. On the benefit side, this treatment may lower your risk for osteoporosis, and perhaps dementia. The final story on hormone replacement therapy has not been written. At the present time, the practice of using hormones in post-menopausal women is discouraged as a general rule. The newer research on estrogen only treatment will likely change some of the thinking on this subject. And additional research on bio-identical hormone replacement may change things yet again. The best advice given the contradictory information currently available is to have a frank discussion with your health care provider. Your treatment should be individualized based upon your risks and the potential benefits of any treatment. While studies can show trends and potential relationships, the exact mechanisms and outcomes will be different from person to person. Your health care provider can use the general guidance from research combined with direct knowledge of your particular case to help dial in the best treatment advice for you.

J.E. Rossouw, G.L. Anderson, R.L. Prentice, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. Journal of the American Medical Association.2002;288(3):321-33. ii Valerie Beral, Gillian Reeves, Diana Bull, Jane Green and for the Million Women Study Collaborators. Breast Cancer Risk in Relation to the Interval Between Menopause and Starting Hormone Therapy. Journal of the National Cancer Institute (2011) 103 (4): 296-305. iii Samuel Shapiro, Richard D T Farmer, Helen Seaman, John C Stevenson and Alfred O Mueck. Does hormone replacement therapy cause breast cancer? An application of causal principles to three studies. Part 1. The Collaborative Reanalysis. Journal of Family Planning and Reproductive Health Care 2011;37:103-109. iv Yasuo Miyoshi, Yoshio Tanji, Tetsuya Taguchi, Yasuhiro Tamaki, and Shinzaburo Noguchi. Association of Serum Estrone Levels with Estrogen Receptor-positive Breast Cancer Risk in Postmenopausal Japanese Women. Clinical Cancer Research June 2003 9; 2229. v Pentii K. Siiteri, Robert I. Sholtz, Piera M. Cirillo, Richard D. Cohen, Roberta E. Christianson, Barbara J. van den Berg, William R. Hopper, and Barbara A. Cohn. Prospective Study of Estrogens During Pregnancy and Risk of Breast Cancer. Public Health Institute. 1967.
i