The Benefits and Discrepancy Regarding Hormone Replacement Therapy for Postmenopausal Women. By: Morgan Lynch BBH 411W: Short Paper 3

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1 The Benefits and Discrepancy Regarding Hormone Replacement Therapy for Postmenopausal Women By: Morgan Lynch BBH 411W: Short Paper 3 Abstract: Hormone Replacement Therapy (HRT) is one of the most recommended treatments for postmenopausal women in order to combat the risks associated with changes in estrogen levels. These risks include endometrial cancer, osteoporosis, immune dysfunction and cardiovascular disease. Current research has provided benefits of HRT in preventing endometrial cancer and osteoporosis. Mixed results however for cardiovascular disease, breast cancer and colorectal cancer exists. This literature review describes some of the recent research regarding HRT and some of these health conditions. The purpose of the writing of this assignment is to fulfill course requirements for BBH 411W and to stand as a personal writing sample, but the findings should not be treated as generalizable research.

2 The average woman will experience menopause in her early to mid-fifties. Postmenopausal women often experience symptoms associated with the decline in ovarian hormones: estrogen, progesterone and testosterone. These hormones serve as protective factors to keep various bodily systems working properly prior to menopause. The absence of these hormones cause symptoms associated with menopause including hot flashes, night sweats, anxiety and lack of sexual drive 1. As menopause extends into postmenopause, a time categorized by the absence of a period for at least a year, the women is at an increased risk for various health conditions such as osteoporosis, cancer, cardiovascular complications, and declined cognitive functioning 2. Hormone replacement therapy (HRT) is often prescribed in order to limit the chances of these potential health risks. Controversy exists however about the risks that hormone replacement therapy itself brings to the individual, a debate that causes many women to forgo treatment. This review hopes to outline what is currently known about the benefits and risks of hormone replacement therapy in order to better understand if HRT is both a safe and effective treatment plan for postmenopausal women. Various studies have outlined the benefits of HRT for postmenopausal women. Specifically, several studies have found protective qualities against several forms of cancer that are more likely to develop in the absence of ovarian hormones. One clinical double-blind trial examined the use of a combined estrogen and progestin therapy in 16,608 postmenopausal women between the ages of 50 and 79. The study hoped to examine the use of HRT in relation to endometrial cancer. In order to be selected for the study the women had to have intact endometrial biopsy results prior to enrollment. This restriction worked to minimize the chances of confounders with preexisting health conditions in relation to endometrial tissue. The study found significantly fewer endometrial cancers in women with the combined hormone therapy than the placebo group

3 (66 vs. 95 endometrial case patients, 95% CI, p = 0.007). The conclusion of this study suggests that HRT can protect women against the development of endometrial cancer 3. In addition to endometrial cancer, breast cancer risk also increases in postmenopausal women. HRT is often recommended as a treatment to decrease this risk. In a randomized clinical trial 27,347 postmenopausal women between 50 and 79 were assigned to either estrogenprogestin combined oral therapy or to a placebo. The study found that women on the combined HRT had initially decreased risk, (hazard ratio = 1.23, 95% CI ), but in later follow up had developed an increased risk (HR = 1.37, 95% CI ). This study did find however than women who took an estrogen-only hormone therapy had decreased breast cancer risk during the intervention as well as in the follow-up (HR 0.55, 95% CI ) 4. This study suggests that estrogen only interventions can decrease the risk of breast cancer in postmenopausal women and may suggest benefits of not combining hormones in future therapies. It is also suggested that postmenopausal changes increase risk for developing colorectal cancer. In a randomized, double blind trial 10,739 postmenopausal women were assigned to either a placebo or estrogen oral therapy. This study did not find a significant difference between the placebo and the treatment group (treatment: HR 1.13, P = 0.43) 5. Based on this study it appears that HRT is not effective in preventing colorectal cancer. Besides cancer, postmenopausal women are also at an increase risk for vascular complications including cardiovascular disease 6. Several studies have confirmed this risk through comparison analysis between aging men and women, finding that the absence of ovarian hormones puts women s cardiovascular system at increased risk for disease 7. HRT has been considered as a treatment for vascular health but there appears to be a lack of sufficient research to support this. In another longitudinal randomized clinical trial, 643 women were assigned to

4 either estrogen-progestin combined therapy or placebo. The trial measured carotid-artery intimamedia thickness (CIMT), which indicates both cholesterol levels that are related to the development of atherosclerosis. The trial found similar results for women in HRT and in placebo, 10 years post-menopause (P = 0.29) 8. Another study on CVD risk found similar results, but also suggested that hormone therapy may even further the risk for developing vascular disease. The combined estrogen-progestin group in this sample had the highest rates of risk in the 1 year follow up (HR 1.54) 9. HRT may not protect women from the increased risk of CVD and may in fact further increase the risk. Although it is fairly certain that cardiovascular disease risk increases after menopause, alternative interventions rather than HRT will need to be considered in order to effectively decrease this risk. One of the major health concerns for postmenopausal women is the risk for osteoporosis, a disease categorized by the degradation of bone mass. Prior to menopause, estrogen works to keep bones healthy by stimulating new bone cell growth. Women with reduced estrogen levels can experience loss in bone density and strength 10. Hormone therapy has also been recommended in order to maintain bone mass. The Women s Health initiative conducted a study in order to assess the effects of hormone therapy and bone density. In this double-blind study, 16,608 women were randomly assigned to a placebo or estrogen-progestin oral therapy group and assessed for any reported fractures during a 5-year period. Among the results, 8.6% of the treatment group experienced a fracture while 11.1% of the placebo group experienced a fracture (HR 0.76, 95% CI ) 11. This study concluded that HRT was beneficial in preventing fractures due to bone density loss. A similar study on HRT and postmenopausal women confirmed results for hormone therapy and bone density, finding that estrogen only supplements were more effective

5 than combination therapies 12. These findings suggest that HRT can increase bone density and therefore protect women from potential fractures. Postmenopausal women experience many unpleasant symptoms in addition to the various increased health risks due to changes in estrogen levels in the body. Current research regarding hormone replacement therapy finds that treatment can be effective in preventing endometrial cancer and loss of bone mass. There is a discrepancy regarding HRT s effect on breast and colorectal cancer, and cardiovascular health. The therapy may in fact contribute to greater chances of developing such conditions as breast cancer. It is also not clear whether estrogenprogestin therapy or estrogen alone is more effective for postmenopausal risks. Further research is needed in order to achieve a better understanding of the potential benefits of HRT as well as the potential harm for postmenopausal women.

6 References 1 Paranjape SG, Turankar, AV, Wakode SL, Dakhale, GN. Estrogen protection against coronary heart disease. Elsevier Journal Koebele, S.V., Bimonte-Nelson H. A. Modeling Menopause: The utility of rodents in translationl behavorial endocrinology. Mauritas May 2 Web MD. Menopause Health Center Chlebowski, R. T. et. al. Continuous Combined Estrogen Plus Progestin and Endometrial Cancer. Oxford University. Journal of National Cancer Institute Dec Chlebowski, R. T. et. al. Breast Cancer After Use of Estrogen Plus Progestin and Estrogen Alone. JAMA: Oncology.2015 June 1. 5 Lavasani, S. et. al. Estrogen and Colorectal Cancer incidence and mortality. American Cancer Society September Ouyang, Pamela M.D. Menopause and Cardiovascular System John s Hopkins Medicine Campesi, I. et. al. Ageing/Menopasual Status in Healthy Women and Men. International Journal of Medical Science February 2. 8 Hodis H. N. et. al. Vascular Effects of Early vs. Late Postmenopausal Treatment with Estradiol. New England Journal of Medicine March Manson, E. Joann et. al. Estrogen pluse Progesting and the Risk of Cardiovascular Heart Disease. The New England Joural of Medicine August Vaananen H. K, Harkonen P. L. Estrogen and Bone Metabolism. Maturitas 1996 May Cauley, Jane et. al. Effects of estrogen plus progestin on risk of bone fracture. The Journal of American Medical Association October Andersson, A. et al. Suppression of Experimental Arthritis and Associated Bone Loss by a Tissue Estrogen Complex Endocrine Society March 15