To HRT or not to HRT, a personal story

Some women sail through perimenopause (the transition from normal periods to none at all) to menopause (complete cessation of periods). Others, on the other hand, do not. For my part I suffered flames of cauldron-like heat lapping up my body, sleepless nights and moods swings more dangerous than a dubious American president next to the nuclear button. The most devastating aspect, however, was the stark choice I faced. I had watched my poor blessed mother, an England VET cycling champion, crumble into a wizen old lady with nerve root impingement at six different levels, after being taken off her HRT. It took years for the pain to subside and for her to come to terms with the fact that until Jesus comes back with the new Heavens and new Earth, she would never ride her bike again. This is osteoporosis, a disorder in which bones are weakened by excessive bone reabsorption and changes in collagen. Oestrogen is key to bone health. Not only does it rebalance the osteoclastic-osteoblastic (bone out-bone in) remodelling process it maintains collagen production (Khastgir et al, 2001). Collagen is the bouncy, water loving substance that makes our skin look youthful. In bones it supports the cancellous and cortical matrix creating a flexible framework for calcium deposition. Without it, bones are brittle, weak and liable to fracture (Studd, 2009). While there are other medications: bisphosphonates; denosumab; and teriparatide, there is evidence that the continuing supplementation of oestrogen via hormone replacement therapy (HRT) is more effective in the prevention of osteoporotic fractures (Trémollieres, 2019, Studd et al, 2009, 1994). BUT HRT carries risk, the most well known being breast cancer. So, the stark choice before me, as I saw it at the time, was this: osteoporosis or cancer, a future like my mum’s or a shortened life. I took to research. Here are my thoughts.

Not being one for pills, my first port of call was the alternatives. I tried them all. Clove had some effect, sage none at all, black cohosh made the symptoms worse and soya gave me migraines. What’s more, when I looked for evidence of efficacy, I found very little. Most articles appeared to be based on opinion and the limited number of studies were, unfortunately, of poor quality, having small cohorts and shaky analysis. Recently, I came across Dr Nitu Bajekal, gynaecologist and lifestyle medical physician. She entirely disagrees. She says they is plenty of peer-reviewed evidence and, if this is your road, her website is well worth a visit. Unfortunately, I hadn’t come across Dr Bajekal at the time so, reluctantly, I began to look into HRT.

James Bertram-Collip, a Canadian researcher, was the chap who discovered HRT. In 1933 he figured out how to extract oestrogen from the urine of pregnant women. Initially it was only used to treat hot flushes and vaginal dryness but by the 1960’s it was seen as the menopausal cure-all. Women, like my mum, were jumping up and down for joy. They would not have to suffer the “change” as their mothers had. Menopause-related ills, such as osteoporosis, were a thing of the past. So, what went wrong?

In 1993 a long-term study was set up by The Women’s Health Initiative (WHI). Its aim was to investigate the health benefits of HRT. Over 161 thousand women were recruited. Their ages ranged age from 50-79 years. The type of HRT tested was Prempro. Prempro consists of Premarin (conjugated equine oestrogen) and Provera (medroxyprogesterone acetate). Some women with medical menopause, those for whom menopause was a result of a hysterectomy, were given just the Premarin, Provera being a guard against uterine cancer. This was a control trail so there were also groups that received a placebo. Results appeared to be devastating. Women taking Prempro seem to demonstrate an increased risk in breast cancer (26%), heart attack (29%), stroke (41%) and blood clots (50%). The study was terminated and, once the results were out, so was the medical and public trust in HRT. Women, like my mum, who had been taking HRT for more than five to ten years were encouraged to stop. But was this the right course of action?

First of all, while the risks listed above appear catastrophic when viewed as percentages, because they relate to a specific population the actual increase, to an individual, is far less. For example, the increased risk of breast cancer to an individual on Prempro works out to be only 0.1% per year (earlymenopause.com). Similar, more digestible, figures are given in the table. Second, re-analyses of the WHI data, showed that the risk of adverse events is more likely to occur in women over sixty or those for whom HRT was initiated ten or more years after their last period (Trémollieres, 2019; Langer, 2017; De Villers, 2016). Later research demonstrated the importance of the mode of drug administration. The WHI study used an oral route, but we now know that venous thromboembolism, stroke and coronary heart disease are less likely to occur if a transdermal form of HRT is used (Renoux et al, 2010; Canonico et al, 2001, 2007; West et al, 2001). There was further good news with respect to breast cancer. Re-consideration of the WHI findings showed that women with no history of HRT usage before the study were no more likely to develop breast cancer than those in the placebo group. In addition, follow up studies demonstrated that women given Premarin on its own exhibited reduced incidence of breast cancer (Anderson et al, 2012). Later studies suggest a similar outcome for women taking HRT in the form of micronized progesterone in association with estradiol (Cordina-Duverger, 2013; Lyytinen ar al, 2009; Fournier et al, 2008) and statistics now demonstrate that these forms of HRT carry the same or less breast cancer risk than alcohol and obesity (British Menopausal Society, 2020). Finally, analysis of the WHI research by Manson et al in 2017 concluded that overall mortality, from any cause, of women aged 50-59 initiating HRT within 10 years of menstruation cessation, was reduced and that this reduction was retained.

So overall, although the WHI study, along with other similar research such as the Million Women Study, appeared to damn the use of HRT, subsequent re-analysis of the same data and further investigation seem to have come out in its favour. Key factors in healthy usage appear to be: age; age of initiation; type and mode of administration; dose; duration; and individual risk profile (Trémollieres, 2019; Horner et al, 2006).

Having digested the evidence and looked at the work of Trémollieres (2019) and Studd (2009, 1994) who extol the physiological benefits of HRT on bone health (Please see my blog: Menopause and osteoporosis), I came to the conclusion that, for me, HRT was the way to go. I did not want to go down the same route as my lovely mum. But HRT is not my only weapon. I also run, lift weights three-four times a week, eat a predominantly plant-based diet with a healthy side order of sardines and tofu and ingest a plethora of bone enhancing vitamins. But I have to tell you, out of all the things I do or take, including the alternatives I have tried, HRT is the one thing that has made my bones feel like living organs again. HRT may not be your choice and that’s fine, we are all different and we all have different risk-benefit profiles. Furthermore, with the growing understanding of the intricacies of hormonal communication during the menopause (Sowers et al, 2007), HRT may be using a sledge hammer to crack a nut. Whatever your thinking, however, I would urge you, along-side medical guidance, to take time to review the evidence. Your future self may well thank you.

For more information about how the osteopathy can help at this time of change please contact Julieann, registered osteopath, at the Osteopath Clapham. Email [email protected] or call 07929595685. You can also book online.

References

Anderson GL, Chlebowski RT, Aragaki AK, et al. (2012) Conjugated equine oestrogen and breast cancer incidence and mortality in postmenopausal women with hysterectomy: extended follow-up of the Women’s Health Initiative randomised trial. Lancet Oncol 2012;13: 476–486

British Menopausal Society (2020) Factsheet. Accessed at https://thebms.org.uk/publications/tools-for-clinicians/. Last accessed 9/6/2020

Cacciatore B, Paakkari I, Hasselblatt R, et al. (2001) Randomized comparison between orally and transdermally administered hormone replacement therapy regimens of long-term effects on 24-hour ambulatory blood pressure in postmenopausal women. Am J Obstet Gynecol 2001;184:904–909

Canonico M, Oger E, Plu-Bureau G, et al. (2007) Oestrogen and Thromboembolism Risk (ESTHER) Study Group. Hormone therapy and venous thromboembolism among postmenopausal women: impact of the route of oestrogen administration and progestogens: the ESTHER study. Circulation 2007; 115:840–845

Cordina-Duverger E, Truong T, Anger A, et al. (2013) Risk of breast cancer by type of menopausal hormone therapy: a case-control study among post-menopausal women in France. PLoS One 2013; 8: e78016

de Villiers TJ, Hall JE, Pinkerton JV, et al. (2016) Revised global consensus statement on menopausal hormone therapy. Climacteric 2016;19: 313–5

Dr Nitu Bajekal https://nitubajekal.com/lifestyle-medicine/ Internet. Accessed 3/6/2020

Early Menopause. https://www.earlymenopause.com/information/hrt-study/ Accessed 2/6/2020 but NO date given for article update. This is important because research and ideas have greatly moved on from the time of WHI and although this article is clear and informative it may be outdated.

Early Menopause. https://www.earlymenopause.com/information/hrt-study/ Internet. Accessed 3/6/2020

Fournier A, Berrino F, Clavel-Chapelon F. (2008) Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study. Breast Cancer Res Treat 2008; 107:103–111.

Horner E, Fleming J, Studd J. (2006) A study of women on long-term hormone replacement therapy and their attitude to suggested cessation. Climacteric 2006;9:459–63

Khastgir G, Studd JWW, Holland N, et al. (2001) Anabolic effect of oestrogen replacement on bone in postmenopausal women with osteoporosis: histomorphometric evidence in a longitudinal study. J Clin Endocrinol Metab 2001;86:289–95

Langer. R (2017) The evidence base for HRT: what can we believe? Pages 91-96 | Received 11 Nov 2016, Accepted 05 Dec 2016, Published online: 10 Mar 2017

Lyytinen H, Pukkala E, Ylikorkala O. (2009) Breast cancer risk in postmenopausal women using estradiol-progestogen therapy. Obstet Gynecol 2009;113:65–73

Manson JE, Aragaki AK, Rossouw JE, et al. (2017) Menopausal hormone therapy and long-term all-cause and cause-specific mortality: the Women’s Health Initiative randomized trials. JAMA 2017;318: 927–938

Renoux C, Dell, aniello S, Garbe E, et al. (2010) Transdermal and oral hormone replacement therapy and the risk of stroke: a nested casecontrol study. BMJ 2010;340:c2519 

Sowers, M., Eyvazzadeh, A., McConnell, D., Yosef, M., Jannausch, M., Zhang, D., Harlow, S., and Randolph, Jr. J., (2007). Anti-Mullerian Hormone and Inhibin B in the Definition of Ovarian Aging and the Menopause Transition. Published online 2008 Jul 1. doi: 10.1210/jc.2008-0567

Studd J, Holland EF, Leather AT, Smith RN. (1994) The dose-response of percutaneous oestradiol implants on the skeletons of postmenopausal women. Br J Obstet Gynaecol 1994;101:787–91

Studd, J. (2009) Oestrogens as first-choice therapy for osteoporosis prevention and treatment in women under 60 CLIMACTERIC 2009;12:206–209

Trémollieres, F. (2019) Assessment and hormonal management of osteoporosis 2019 ISSN: 1369-7137 (Print) 1473-0804 (Online) Journal homepage: https://www.tandfonline.com/loi/icmt20

West SG, Hinderliter AL, Wells EC, et al. (2001) Transdermal estrogen reduces vascular resistance and serum cholesterol in postmenopausal women. Am J Obstet Gynecol 2001;184:926–933

WHI https://www.whi.org/SitePages/WHI%20Home.aspx Internet. Accessed 2/6/2020