Hormone Replacement Therapy and its Risks and Benefits for Women

Ronald S. Laura, DPhil

Professor, School of Education, Faculty of Education and Arts, The University of Newcastle, Callaghan NSW 2308, Australia; Tel. +61 2 4921 5942; Fax: +61 2 4921 7887; E-mail: ron.laura@newcastle.edu.au

INTRODUCTION

The Decline of Hormones Due to Ageing

There is no doubt that as both women and men age, the decline in the hormones which in their earlier years kept them vigorous and youthful has impacted dramatically on their health. Hormonal balance plays an integral role in maintaining the physiological integrity of the body and mind functions of both sexes. For example, hormone balance regulates a wide array of physiological and cognitive functions such as the metabolisation of proteins, carbohydrates, minerals, and body fats.¹ It is the efficacy of hormonal interactions that also govern the production of DNA and RNA, along with enzyme functionality. Research has shown that hormonal balance features prominently in the response to the body and mind to stress, blood sugar balance and the regulation of diabetes, kidney function, libido, menstruation and menopause, to name only a few facets of its capability.² Hormones also serve as catalysts which assist in the regulation of the synthesis of cellular proteins. Given that hormones influence a wide range of bodily processes, it is evident that the decline in hormonal levels impedes the efficiency of the communicative receptor exchanges within the endocrine system itself.³ This deficiency, in turn, compromises a number of integrated  systems which interconnect with each other, thereby diminishing cardiovascular and immune functions, detoxification mechanisms, and gastrointestinal efficacy.⁴

Evidence-based clinical research has established that various hormones decline significantly in many individuals, both men and women, as young as 25 years old. For example, with regard to important factors requisite for good health, the diminution of growth hormone, dehydroepiandrosterone (DHEA), and testosterone are reported to exhibit a 50% decline between the ages of 25 and 50 years old.⁵

More significantly the diminution of these hormones drops another 50% between the ages of 50 and 75 years old.⁶ From 25 to 50 years old women lose 30% of their estrogen, followed by a slow but continual decline in estrogen for the rest of their lives.⁷ The most significant hormonal decline is progesterone with a 75% decline from age 35 to 50.⁸ Within the context of menopause, it is clear that the erosion of these essential hormones represents a serious threat to the well-being of women. This being so, the reliance on hormone replacement therapy (HRT) has burgeoned exponentially.

THE RISKS AND BENEFITS OF HORMONE REPLACEMENT THERAPY (HRT)

The etymology of the word ‘ hormone’ leads us to the Greek word ‘hormao’ meaning to excite, to animate, or to enliven.⁹ Hormones are secreted predominantly from the endocrine glands and absorbed into the bloodstream. The hormones that have been most commonly utilised in HRT are progesterone, estrogen, testosterone, adrenal hormones, DHEA, thyroid hormones, pregnenolone, melatonin, and human growth hormone.¹⁰ The problem is that different combinations of the hormones which constitute HRT have in many cases displayed beneficial effects, while in other cases the health risks have outweighed the benefits. The controversy and debate about the virtues and liabilities of HRT have encouraged a much wider context of investigation and evidence-based assessment. After more than a decade of fear and uncertainty regarding HRT, the outcomes of  recent studies have afforded a degree of helpful clarity regarding the balance of risks and benefits.¹¹ It is now accepted that factors such as the age of a woman and the years since menopause commenced and ended have greatly influenced the profile for HRT virtue and liability.¹² Research has now shown that the virtues of HRT outweigh the liabilities for menopausal women who are less than 60 years of age or within 10 years of having commenced menopause. For instance, when HRT has been utilised and initiated in the early stages of menopause, there is evidence that appears to confirm that the progression of atherosclerotic disease can be significantly slowed, thereby minimising the risk of cardiovascular disease and risk of mortality.¹³ During this ‘window of opportunity’ HRT has also been shown to provide protection against cognitive decline and senility.¹⁴ In older women and women more than 10 years past menopause, the risk-benefit balance of HRT is less favorable, “particularly with regard to cardiovascular risk and cognitive impairment”.¹⁵ Despite the risk factors associated with the previous case study, the use of HRT in those cases where menopause has commenced prematurely (<40 years), HRT has succeeded in ameliorating the risk of cardiovascular disease, osteoporosis, and cognitive decline.¹⁶ There is strong evidence to demonstrate that the ‘non-oral’ administration of estrogen provides advantages. Similarly, the duration of combined HRT use is ideally limited to less than 5 years, in as much as the risk of breast cancer has been shown to ascend after 3-5 years of use.¹⁷

When all is said, it is evident that HRT represents a major breakthrough in the treatment of hormonal imbalance and hormone restoration. It is also clear that a more holistic approach is needed to ensure that the decision to introduce HTR in the context of menopause is holistically personalised to suit the individual involved, as the hormonal balance of every woman is unique and cognitively designated. Factors that cause an imbalance in women’s hormones may also be an issue of lifestyle. The following simple considerations could make a huge difference to your own control of your hormonal balance:

• Be cautious of foods that have hormones added to them such as commercially produced meat, eggs, and dairy products;
• Be wary of herbs that have an estrogenic effect on their bodies such as licorice, black cohosh, and damiana;
• Be wary of oral contraceptive pills and hormone replacement therapies which have high estrogenic components;
• Be wary of exposure to radiation which increases the levels of estrogen in their blood;
• Be wary of chronic constipation which interferes with the body’s ability to eliminate estrogen, leading to a buildup of estrogen in the colon and re-absorption by the body.

1. Lobo RA. Where are we 10 years after the Women’s Health Initiative? J Clin Endocrinol Metab. 2013; 98(5): 1771-1780. doi: 10.1210/jc.2012-4070

2. National Institute for Health and Care Excellence. Menopause: Clinical guideline – methods, evidence and recommendations, (NG23), Version 1.5. Web site. www.nice.org.uk/guidance/ng23/evidence/fullguideline-559549261. Accessed November 12, 2016.

3. Panay N, Hamoda H, Arya R, Savvas M, British Menopause Society, Women’s Health Concern The 2013 British Menopause Society and Women’s Health Concern recommendations on hormone replacement therapy. Menopause Int. 2013; 19(2): 59-68. doi: 10.1177/1754045313489645

4. Manson JE, Chlebowski RT, Stefanick ML, et al. Menopausal hormone therapy and health outcomes during the intervention and extended post stopping phases of the Women’s Health Initiative randomized trials. JAMA. 2013; 310: 1353-1368. doi: 10.1001/jama.2013.278040

5. de Villiers TJ, Pines A, Panay N, et al. Updated 2103 International Menopause Society recommendations on menopausal hormone therapy and preventive strategies for midlife health. Climacteric. 2013; 16: 316-337. doi: 10.3109/13697137.2013.795683

6. National Institute for Health and Care Excellence. Menopause: diagnosis and management of menopause. (NICE guideline 23.). Web site. www.nice.org.uk/guidance/ng23. Accessed November 12, 2016.

7. Woods NF, Mitchell ES. Sleep symptoms during the menopausal transition and early postmenopause: Observations from the Seattle Midlife Women’s Health Study. Sleep. 2010; 33(4): 539-549. doi: 10.1093/sleep/33.4.539

8. Baber RJ, Panay N; The IMS Writing Group. 2016 IMS recommendations on women’s midlife health and menopause hormone therapy. Climacteric. 2016; 19: 109-150. doi: 10.3109/13697137.2015.1129166

9. Hodis HN, Mack WJ. Hormone replacement therapy and the association with coronary heart disease and overall mortality: Clinical application of the timing hypothesis. J Steroid Biochem Mol Biol. 2013. [Epub ahead of print.] doi: 10.1016/j.jsbmb.2013.06.011

10. Compston J, Cooper A, Cooper C, et al; on behalf of the National Osteoporosis Guideline Group (NOGG). Diagnosis and management of osteoporosis in postmenopausal women and older men in the UK: National Osteoporosis Guideline Group (NOGG); March 2014. doi: 10.1016/j.maturitas.2013.05.013

11. Scientific Advisory Committee on Nutrition: Vitamin D and Health. Web site. www.gov.uk/government/groups/scientific-advisory-committee-on-nutrition. Accessed November 12, 2016.

12. Mann E, Smith MJ, Hellier J, et al. Cognitive behavioural treatment for women who have menopausal symptoms after breast cancer treatment (MENOS 1): A randomised controlled trial. Lancet Oncol. 2012; 13,: 309-318. doi: 10.1016/S1470-2045(11)70364-3

13. Kanis JA, Harvey NC, Cooper C, et al. A systematic review of intervention thresholds based on FRAX: A report Prepared for the National Osteoporosis Guideline Group and the International Osteoporosis Foundation. Advisory Board of the National Osteoporosis Guideline Group. Arch Osteoporos. 2016; 11: 25. doi: 10.1007/s11657-016-0278-z

14. Collins P, Webb CM, de Villiers TJ, et al. Cardiovascular risk assessment in women – an update. Climacteric. 2016; 19: 329-336. doi: 10.1080/13697137.2016.1198574

15. Hodis HN, Mack WJ, Henderson VW, et al. ELITE Research Group. Vascular effects of early versus late postmenopausal treatment with estradiol. N Engl J Med. 2016; 374: 1221-1231. doi: 10.1056/NEJMoa1505241

16. Gleason CE, Dowling NM, Wharton W, et al. Effects of hormone therapy on cognition and mood in recently postmenopausal women: findings from the randomized, controlled KEEPS-Cognitive and Affective Study. PLoS Med. 2015; 12: e1001833. doi: 10.1371/journal.pmed.1001833

17. Shumaker SA, Legault C, Kuller L, et al. Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women’s Health Initiative Memory Study. JAMA. 2004; 291: 2947-2958. doi: 10.1001/jama.291.24.2947