This is one area in medicine where the treatment is quite simple and the effects are truly transformative.
“We argue for a new approach that goes beyond the treatment of specific symptoms, to encompass a broad model to support women transitioning this life stage, using the model of empowerment,” write the authors of the first of four Lancet papers about menopause.
The series is timed for International Women’s Day, whose theme this year is “Count Her In: Invest in Women. Accelerate. Progress.”
“WHO defines empowerment as an active process of gaining knowledge, confidence, and self-determination to self-manage health and make informed decisions … in which the patient is an expert in their own condition and the health-care worker supports the patient to become an equal and active partner in managing their own care,” the writers continue.
I applaud the authors of this opening statement. As a GP who specialises in women’s hormonal health this is exactly my wish list.
But after this strong start, the authors suggest that “a medicalised view of menopause disempowers women”. The paper cited (Steptoe et al., Lancet, 14 Feb. 2015) neither supports nor discusses this opinion, but instead reports the lowest levels of wellbeing in ages 45-54 years in high-income countries – the typical years of menopausal transition in these populations.
I’ll discuss these papers in some detail, but first I want to share a case study, with the patient’s permission.
A 38-year-old married mum of two came to see me as a new patient in 2015. She complained of anxiety, low mood, insomnia, mental and physical fatigue, severe generalised pain and electric shock feelings zapping all over her body. She could not think clearly and had very little energy.
She had already been seen by several specialities: endocrinology, cardiology, psychiatry and neurology, including a voluntary inpatient psychiatric stay. Extensive bloods, MRIs of brain and spine, CTs and an EEG were all normal. She had no prior mental health issues.
She had reacted badly to a trial of thyroxine for a borderline TSH, developing severe insomnia, anorexia and weight loss that required benzodiazepines, which she struggled to come off. She had an even worse reaction to a general anaesthetic for a complication post-pregnancy. But she muddled on.
A new psychiatrist and neurologist suggested low-dose amitriptyline, which allowed her to function at an acceptable level, albeit with extreme fatigue. In 2018 she attended with menorrhagia and mentioned she was divorcing, but amicably. She didn’t want to risk the hormones in a Mirena nor the anaesthetic required for an ablation. So, she muddled on with iron infusions and tranexamic acid.
In September 2022, aged 44, she attended with night sweats and the diagnosis was easy.
It turned out there was a strong history of premature ovarian insufficiency in her close family. She decided to risk the anaesthetic for an ablation and two weeks later we started cyclical body-identical oestradiol and progesterone.
In three weeks, she said she felt like a new person. Testosterone was added after four months for her persistent fatigue, poor concentration and loss of libido and 12 months later she said she was back to her old self.
The patient has graciously allowed me to share her story so that other women do not lose precious years of their lives.
In answer to the Lancet papers
When a woman stops ovulating, her oestradiol and progesterone fall to an undetectable level, and she is now deficient in these hormones compared to when they did produce them.
This is a mathematical fact. How it is described is personal choice.
I attended a lecture on updates in antenatal care last week and learned that the maternal mortality rate in Nigeria is currently 1% while in Australia it is 0.006%. Pregnancy and childbirth are a natural part of life but we offer women medical support.
The Lancet authors, led by Professor Martha Hickey from the Royal Women’s Hospital in Melbourne, suggest that the most women can “navigate menopause without treatment” (no supporting evidence). I agree women are incredibly resilient, often tolerating significant symptoms such as heavy menstrual bleeding. Many women do “navigate” menopause alone, but I do not think that the majority would call it plain sailing.
The authors of the third paper challenge menopause transition causing depression despite extensive literature linking sex hormones to mood. My professional experience is that many patients experience anxiety, insomnia, low mood, anhedonia, irritability and rage, often starting many years before the end of menstruation. Some of these women will have a history of other reproductive mood disorders, such as PMDD, perinatal depression or mood disorders secondary to contraception. Other women often notice a worsening of depression and anxiety.
I agree that women in menopause transition are often managing significant psychosocial stress, with many juggling work and intergenerational family care. But MHT alone has improved mood symptoms for many of my patients, for some completely alleviating them. For others incorporating psychological modalities such as CBT and EMDR has been key and some have required antidepressants.
MHT also seems to enable women to make better health behaviour decisions including improving nutrition, exercise, social connection, and reducing or ceasing alcohol.
Yet current rates of MHT prescribing are very low, globally averaging 5% and only 14% in Australia, while 20% of women in Australia aged 45-64 are prescribed antidepressants.
The authors suggest that this medicalisation of menopause has provided a “glittering prize” for the pharmaceutical industry. It is surprising therefore that none of the big pharmaceutical companies currently make body-identical hormone therapy.
I believe that pharmaceutical companies stand to make much greater profit from the average woman who is not on hormone therapy as she is at higher risk of both suffering many symptoms and future chronic disease, requiring many more medications than MHT.
The gold standard drug treatment for menopause is MHT, which should be body-identical.
To quote studies that used synthetic progestins, such as the Women’s Health Initiative, as being synonymous with progesterone is misleading, and this frequently occurs in the medical literature as it has in this series. The authors accept that oestradiol alone reduces the lifetime risk of breast cancer but neglect the evidence showing oestradiol combined with micronised progesterone also does not increase breast cancer risk.
Related
Women now spend a significant part of their lives after or in menopause. Oestrogen confers a health advantage to women until menopause and it is likely this that means a greater life expectancy. But what most people want is health span, the ability to live as well as you can for as long as you can. While women live longer than men on average, they do so with four times the rate of debilitating disease than their male contemporaries by the age of 65, according to the ABS.
The role of reducing chronic disease when women experience an early menopause or POI is accepted, but its role in disease prevention when used in normal menopause is challenged. Body-identical MHT has been shown in women of all ages to reduce osteoporosis, cardiovascular disease, dementia and colorectal cancer.
The final article discussing menopause after cancer provides excellent reassurance about vaginal oestrogen safety even for breast cancer survivors. There is now overwhelming evidence that this is a safe and effective treatment for genitourinary syndrome of the menopause, treating symptoms and reducing urinary tract infections and the associated morbidity and mortality thereof. There is a mention of the new drug for vasomotor symptoms, fezolinetant, which readers most note has not been trialled in survivors of breast cancer.
Shared decision making should include women with a history of hormone receptor-positive breast cancer. The WHI is repeatedly cited and there is no mention of new information such as oestradiol being used to improve outcomes in triple negative breast cancer (ClinicalTrials.gov ID NCT03941730), or that the dominant oestrogen in menopause, oestrone, could be the tumorigenic oestrogen in breast cancer.
How we can provide better care
While there can be many areas in medicine that are difficult to treat, this is one area where the treatment is actually quite simple, and the effects are truly transformative. Women on MHT often find they no longer need to reduce their work demands nor change their job.
As doctors we can literally raise the glass ceiling for women in the workplace, improving both their financial independence and the economy as a whole – that’s what I call “investing in women”.
Early perimenopause symptoms are often a result of changing levels of neurotransmitters in the brain including, fatigue, irritability, loss of joy, anxiety, depressed mood, intrusive thoughts and insomnia.
Heavy periods are often the first thing a woman comes to see us about, and we can be distracted by the resulting iron deficiency as the sole cause for her tiredness. Palpitations, recurrent UTIs, itchy skin, pins and needles, dry eyes, joint pain – every speciality can be involved in a perimenopausal woman’s care. Hot flushes and night sweats are often a later symptom, and 25% of women never have any.
A significant number of women will be perimenopausal by their late 30s, because although the average age of menopause is 51, many women will go through menopause earlier.
There is no diagnostic test for perimenopause. FSH LH estradiol and progesterone are usually normal in perimenopause. FSH will only rise once there has been persistent failure of ovulation.
For some women, just understanding why they are having these symptoms is enough. But for the majority, having the option to try hormone therapy, which not only treats their symptoms but reduces their future risk of disease.
This affects our workforce too
It is not just our female patients that we must consider in this discussion. Over 50% of Australian GPs are women and half of those are aged 45-64. Those doctors experiencing severe menopause symptoms will be affected at work. Some 73% GPs report feelings of burnout in the last 12 months (RACGP Health of the Nation 2022). Burnout in doctors is linked to clinical errors – and there is significant overlap between “burnout” and menopause transition.
The ABS reports that many women reduce their hours or leave their jobs in midlife, earlier than they had intended, and often due to ill health. The average age of retirement is 52, one year after the average age of menopause. This is unlikely to be coincidental.
Doctors are no different. But we can even be worse at seeking help for mental health problems than the general population and occupational health doctors can also be poor at recognising menopause as a cause.
Given that all doctors will encounter women in perimenopause or menopause and all female doctors will experience it if they live long enough, we must educate ourselves on perimenopause and menopause and the simple, safe, and effective treatments that are available for our patients and ourselves.
Safe medicine with a world of benefits
Women and especially women of colour continue to be underserved by the scientific community and its focus on the caucasian male model of disease.
But there is some fascinating research into the applications of giving back sex hormones to women. I do not think I can be alone in my excitement on finding that oestriol shows promise in treating multiple sclerosis or that progesterone can treat perinatal anxiety or has promise for PTSD. These treatments have real implications for my patients.
I no longer rely on abstracts, summaries and meta-analysis by others. So many studies contain excellent data, but the conclusion is often no more than an opinion piece. My own reading of thousands of original studies on body-identical hormone therapy is that it is safe for the majority of women, it can treat a vast array of symptoms given sex hormone receptors are everywhere in the body and it can reduce the risk of many of our chronic diseases. But please fact check with the reference list below.
All people should be empowered with knowledge to make choices that are right for them. This is true shared decision making, with an educated doctor and informed patient at its centre.
As a GP I will continue to read the research myself, learn from my patients and not look to ivory towers for support.
Dr Ceri Cashell started her career in general practice in 2004 in Edinburgh but since 2012 she has been working in Avalon, Sydney, where she is a practice principal and owner. She is a passionate advocate for increased awareness of the effects of hormones on physical and mental health.
References
Steptoe A, Deaton A, Stone AA. Subjective wellbeing, health, and ageing. Lancet. 2015 Feb 14;385(9968):640-648. doi: 10.1016/S0140-6736(13)61489-0. Epub 2014 Nov 6. PMID: 25468152; PMCID: PMC4339610.
Kiran A, Geary RS, Gurol-Urganci I, et al Sociodemographic differences in symptom severity and duration among women referred to secondary care for menorrhagia in England and Wales: a cohort study from the National Heavy Menstrual Bleeding Audit BMJ Open 2018;8:e018444. doi: 10.1136/bmjopen-2017-018444
Andreano JM, Touroutoglou A, Dickerson B, Barrett LF. Hormonal Cycles, Brain Network Connectivity, and Windows of Vulnerability to Affective Disorder. Trends Neurosci. 2018 Oct;41(10):660-676. doi: 10.1016/j.tins.2018.08.007. Epub 2018 Sep 25. PMID: 30274602; PMCID: PMC6481680.
Stefaniak M, Dmoch-Gajzlerska E, Jankowska K, Rogowski A, Kajdy A, Maksym RB. Progesterone and Its Metabolites Play a Beneficial Role in Affect Regulation in the Female Brain. Pharmaceuticals (Basel). 2023 Mar 31;16(4):520. doi: 10.3390/ph16040520. PMID: 37111278; PMCID: PMC10143192.
de Oliveira Costa J, Gillies MB, Schaffer AL, Peiris D, Zoega H, Pearson S-A. Changes in antidepressant use in Australia: A nationwide analysis (2015–2021). Australian & New Zealand Journal of Psychiatry. 2023;57(1):49-57. doi:10.1177/00048674221079740
Abenhaim HA, Suissa S, Azoulay L, Spence AR, Czuzoj-Shulman N, Tulandi T. Menopausal Hormone Therapy Formulation and Breast Cancer Risk. Obstet Gynecol. 2022 Jun 1;139(6):1103-1110. doi: 10.1097/AOG.0000000000004723. Epub 2022 May 3. PMID: 35675607.
Yang XP, Reckelhoff JF. Estrogen, hormonal replacement therapy and cardiovascular disease. Curr Opin Nephrol Hypertens. 2011 Mar;20(2):133-8. doi: 10.1097/MNH.0b013e3283431921. PMID: 21178615; PMCID: PMC3123884
Gosset A, Pouillès JM, Trémollieres F. Menopausal hormone therapy for the management of osteoporosis. Best Pract Res Clin Endocrinol Metab. 2021 Dec;35(6):101551. doi: 10.1016/j.beem.2021.101551. Epub 2021 Jun 2. PMID: 34119418.
Hodis HN, Mack WJ. Menopausal Hormone Replacement Therapy and Reduction of All-Cause Mortality and Cardiovascular Disease: It Is About Time and Timing. Cancer J. 2022 May-Jun 01;28(3):208-223. doi: 10.1097/PPO.0000000000000591. PMID: 35594469; PMCID: PMC9178928.
Kim YJ, Soto M, Branigan GL, Rodgers K, Brinton RD. Association between menopausal hormone therapy and risk of neurodegenerative diseases: Implications for precision hormone therapy. Alzheimers Dement (N Y). 2021 May 13;7(1):e12174. doi: 10.1002/trc2.12174. PMID: 34027024; PMCID: PMC8118114
Mørch LS, Lidegaard Ø, Keiding N, Løkkegaard E, Kjær SK. The influence of hormone therapies on colon and rectal cancer. Eur J Epidemiol. 2016 May;31(5):481-9. doi: 10.1007/s10654-016-0116-z. Epub 2016 Jan 12. PMID: 26758900.
McVicker L, Labeit AM, Coupland CAC, Hicks B, Hughes C, McMenamin Ú, McIntosh SA, Murchie P, Cardwell CR. Vaginal Estrogen Therapy Use and Survival in Females With Breast Cancer. JAMA Oncol. 2024 Jan 1;10(1):103-108. doi: 10.1001/jamaoncol.2023.4508. PMID: 37917089; PMCID: PMC10623297.
Tan-Kim J, Shah NM, Do D, Menefee SA. Efficacy of vaginal estrogen for recurrent urinary tract infection prevention in hypoestrogenic women. Am J Obstet Gynecol. 2023 Aug;229(2):143.e1-143.e9. doi: 10.1016/j.ajog.2023.05.002. Epub 2023 May 11. PMID: 37178856.
Qureshi R, Picon-Ruiz M, Aurrekoetxea-Rodriguez I, Nunes de Paiva V, D’Amico M, Yoon H, Radhakrishnan R, Morata-Tarifa C, Ince T, Lippman ME, Thaller SR, Rodgers SE, Kesmodel S, Vivanco MDM, Slingerland JM. The Major Pre- and Postmenopausal Estrogens Play Opposing Roles in Obesity-Driven Mammary Inflammation and Breast Cancer Development. Cell Metab. 2020 Jun 2;31(6):1154-1172.e9. doi: 10.1016/j.cmet.2020.05.008. PMID: 32492394.
Voskuhl RR, Wang H, Wu TC, Sicotte NL, Nakamura K, Kurth F, Itoh N, Bardens J, Bernard JT, Corboy JR, Cross AH, Dhib-Jalbut S, Ford CC, Frohman EM, Giesser B, Jacobs D, Kasper LH, Lynch S, Parry G, Racke MK, Reder AT, Rose J, Wingerchuk DM, MacKenzie-Graham AJ, Arnold DL, Tseng CH, Elashoff R. Estriol combined with glatiramer acetate for women with relapsing-remitting multiple sclerosis: a randomised, placebo-controlled, phase 2 trial. Lancet Neurol. 2016 Jan;15(1):35-46. doi: 10.1016/S1474-4422(15)00322-1. Epub 2015 Nov 29. PMID: 26621682.
Tapilskaya N.I., Nekrasov M.S., Krikheli I.O., Ob’edkova K.V., Gzgzyan A.M., Kogan I.Y., Glushakov R.I. Stress-protective effects of micronized progesterone in treatment of anxiety disorders in pregnant women after in vitro fertilisation // Gynecology. – 2021. – Vol. 23. – N. 4. – P. 346-353. doi: 10.26442/20795696.2021.4.201091
Ralevski E, Newcomb J, Pisani E, DeNegre D, Peltier M, Jane JS, Yoon G, Petrakis I. Progesterone Attenuates the Stress Response in Individuals with Alcohol Dependence and Post-Traumatic Stress Disorder – A Pilot Study. J Dual Diagn. 2024 Jan-Mar;20(1):39-51. doi: 10.1080/15504263.2023.2294989. Epub 2024 Feb 1. PMID: 38147491.
Hodis HN, Mack WJ. Menopausal Hormone Replacement Therapy and Reduction of All-Cause Mortality and Cardiovascular Disease: It Is About Time and Timing. Cancer J. 2022 May-Jun 01;28(3):208-223. doi: 10.1097/PPO.0000000000000591. PMID: 35594469; PMCID: PMC9178928.
Gosset A, Pouillès JM, Trémollieres F. Menopausal hormone therapy for the management of osteoporosis. Best Pract Res Clin Endocrinol Metab. 2021 Dec;35(6):101551. doi: 10.1016/j.beem.2021.101551. Epub 2021 Jun 2. PMID: 34119418.
Kim YJ, Soto M, Branigan GL, Rodgers K, Brinton RD. Association between menopausal hormone therapy and risk of neurodegenerative diseases: Implications for precision hormone therapy. Alzheimers Dement (N Y). 2021 May 13;7(1):e12174. doi: 10.1002/trc2.12174. PMID: 34027024; PMCID: PMC8118114.
Fernandez E, La Vecchia C, Braga C, Talamini R, Negri E, Parazzini F, Franceschi S. Hormone replacement therapy and risk of colon and rectal cancer. Cancer Epidemiol Biomarkers Prev. 1998 Apr;7(4):329-33. PMID: 9568789.
Abenhaim HA, Suissa S, Azoulay L, Spence AR, Czuzoj-Shulman N, Tulandi T. Menopausal Hormone Therapy Formulation and Breast Cancer Risk. Obstet Gynecol. 2022 Jun 1;139(6):1103-1110. doi: 10.1097/AOG.0000000000004723. Epub 2022 May 3. PMID: 35675607.
Geukes M, van Aalst MP, Robroek SJ, Laven JS, Oosterhof H. The impact of menopause on work ability in women with severe menopausal symptoms. Maturitas. 2016 Aug;90:3-8. doi: 10.1016/j.maturitas.2016.05.001. Epub 2016 May 4. PMID: 27282787.
Li CJ, Shah YB, Harness ED, Goldberg ZN, Nash DB. Physician Burnout and Medical Errors: Exploring the Relationship, Cost, and Solutions. Am J Med Qual. 2023 Jul-Aug 01;38(4):196-202. doi: 10.1097/JMQ.0000000000000131. Epub 2023 Jun 29. PMID: 37382306.
Converso D, Viotti S, Sottimano I, Loera B, Molinengo G, Guidetti G. The relationship between menopausal symptoms and burnout. A cross-sectional study among nurses. BMC Womens Health. 2019 Nov 27;19(1):148. doi: 10.1186/s12905-019-0847-6. PMID: 31775724; PMCID: PMC6882317.
Wijeratne C, Johnco C, Draper B, Earl J. Doctors’ reporting of mental health stigma and barriers to help-seeking. Occup Med (Lond). 2021 Nov 6;71(8):366-374. doi: 10.1093/occmed/kqab119. PMID: 34534344.
Geukes M, Oosterhof H, van Aalst MP, Anema JR. Attitude, confidence and social norm of Dutch occupational physicians regarding menopause in a work context. Maturitas. 2020 Sep;139:27-32. doi: 10.1016/j.maturitas.2020.05.015. Epub 2020 May 28. PMID: 32747037.
