Marketing perimenopause, for fun and profit
Part 1 of The Menopause Files
I put out a call to my (very much appreciated) paid subscribers recently, for suggestions on contentious health and nutrition topics that they would like me to investigate. The following comment grabbed my attention, as I had been thinking for quite a while about doing a deep dive on the renewed push to prescribe hormone therapy to menopausal women.
In this first part of what will, no doubt, burgeon into a multi-part series, we'll explore the carefully-crafted rise to public prominence of the previously little-known term, perimenopause, investigate who and what is behind that rise, and find out which of the myriad symptoms attributed to perimenopause are truly driven by the hormonal changes that all mid-life women undergo.
To briefly recap the menopausal hormone therapy saga, so-called estrogen replacement therapy (ERT) for menopausal symptoms was launched in the late 1950s, with prescriptions skyrocketing after the publication of pharmaceutical industry-funded American gynaecologist Robert Wilson's 1966 book Feminine Forever. Far from being "a silent topic for past generations", my grandmother and her contemporaries were bombarded with messaging about the woes of menopause and the relief they (and their husbands) could obtain from taking the magical estrogen elixir. In fact, by the mid-1960s ERT was the most commonly prescribed medication in British women aged 50–64, with around one third of this demographic taking it.
Check out these completely cringe-worthy ERT ads from the 1950s and 60s:
The revelation in the mid-1970s that ERT caused a roughly eight-fold increase in endometrial cancer risk in women who still had an intact uterus (i.e. had not undergone hysterectomy) temporarily reduced its popularity, until pharmaceutical companies developed combination estrogen-progestin (synthetic progesterone) products, now rebranded as 'hormone replacement therapy' (HRT). Throughout the 1980s, HRT prescription rates soared once again, not just among women complaining of menopausal vasomotor symptoms (hot flushes and night sweats), but also in healthy, asymptomatic women who were sold on the treatment on the basis of observational studies that found reduced rates of cardiovascular disease in postmenopausal women taking HRT. And the ads were still cringey:
Then, in 2002, results from the Women’s Health Initiative hormone therapy trials were published. The arm of the trial in which women who had not undergone a hysterectomy were randomised to receive either equine (horse-derived) estrogen plus a progestin (synthetic progesterone) was halted early, because more women in the combination HRT arm developed coronary heart disease (CHD), stroke, and pulmonary embolism, than those taking placebo. So much for HRT being cardioprotective! The absolute excess risks of cardiovascular disease attributable to combination HRT were not huge; for every 10 000 woman-years on estrogen plus progestin, there were seven more coronary heart disease events, eight more strokes, and five more pulmonary embolisms (as well as six fewer colorectal cancers and five fewer hip fractures). It was the finding that combination HRT increased the risk of breast cancer, however - eight more invasive breast cancers per 10 000 woman-years on HRT - that caused the most terror among women, resulting in a precipitous decline in prescriptions for HRT.
However, in recent years, I have noticed a resurgence in the promotion of HRT - now rebranded 'menopausal hormone therapy' or MHT - by professional societies and individual doctors with close ties to the pharmaceutical industry. In conjunction with a strong push to discredit the Women's Health Initiative trial findings, and to resurrect the public image of hormone therapy for mid-life women, I've also observed a massive increase in online and offline discussion of 'the perimenopause' as a phase of women's lives that is particularly problematic.
Perimenopause is the rather vaguely-defined period before and after women go through menopause; menopause is defined as the very final menstrual period, but can only be identified in retrospect, after a women has not had a period for 12 months.
Here's a snapshot of Google search trends for 'perimenopause' in Australia, from 2004 to the present, which graphically illustrates the recent explosion of public interest in this previously obscure term:
Articles, videos and podcast episodes devoted to the travails of perimenopause have mushroomed, while entrepreneurial doctors, health coaches and personal trainers have swarmed to the rapidly-growing niche of 'perimenopause specialist' like flies to cow dung. The online content they're consuming and the other practitioners they've consulted have persuaded many of my forty-something female clients that every physical and psychological symptom they experience is attributable to perimenopause. Meanwhile, supplement companies are cashing in with pills and potions targeted at perimenopausal women.
Do you know what this all smells like to me? Disease mongering. Disease mongering, as I discussed in 5 reasons to think twice before taking an antidepressant, is
"the process by which those who sell and deliver treatments (including drug companies and doctors) widen the diagnostic boundaries of illnesses, or simply invent diseases to match the treatments they have developed, and then market awareness of these diseases to the ‘worried well’."
Osteoporosis, erectile dysfunction and social phobia are all examples of disease mongering. As explained in 'Selling sickness: the pharmaceutical industry and disease mongering', pharmaceutical companies which developed drugs for these conditions are well-documented to have engaged public relations companies to place articles in the media emphasising their prevalence and severity; set up and poured money into astroturf foundations devoted to raising public awareness of them; and funded prominent doctors to develop 'medical education' programs to persuade their fellow clinicians to diagnose and prescribe treatment for them.
Disease mongering is not confined to mainstream medicine; it's rife in 'alternative medicine' too. When I was in naturopathic college, 'candida syndrome' was a popular explanation for people suffering from general malaise which couldn't be explained by any established medical diagnosis. Books on this mysterious syndrome (yes, books - this was pre-internet, folks) contained long lists of symptoms that people suffering from it might experience. Problem was, roughly 98 per cent of people on the planet would have had most or all of those symptoms at some point in their lives, and it was hard to fathom how almost everyone could be suffering from rampant yeast overgrowth without being a helluva lot sicker than they were. A couple of years later, candida syndrome's star had waned, and most of those nebulous symptoms were now attributed to a new trendy diagnosis, 'adrenal fatigue'. Soon after I started my practice, I saw a whole series of clients who had been diagnosed by a local 'complementary' doctor with 'reactive hypoglycaemia', on the basis of symptoms that had previously been attributed to candida syndrome and adrenal fatigue. As you can imagine, I was starting to see a pattern!
So when I come across lists of 34 symptoms of perimenopause (including 'brain fog', bloating, hair loss, weight gain, mood swings and irritability) and 40 symptoms of menopause (from lack of motivation to difficulty concentrating to muscle aches and joint pains) I get that déjà vu feeling, all over again. Hey, weren't most of those symptoms previously ascribed to candida syndrome, adrenal fatigue and reactive hypoglycaemia? It sure looks to me like the disease mongers are hard at work again.
What is the evidence that the grab-bag of physical and psychological maladies ascribed to perimenopause and menopause are actually attributable to the winding-down of women's reproductive function? Here's a clue: When researchers ask men and women of various ages if they experience any of the symptoms commonly attributed to menopause, without giving any clues that the study is menopause- or hormone-related, both sexes report experiencing all of these symptoms (except the sex-specific ones like breast tenderness) at varying levels of intensity, throughout their lives. Only the vasomotor symptoms, hot flushes and night sweats, definitively cluster around the age of menopause.
For example, here are the results of questionnaires sent to British men and women aged 30-64 years:
As you can see, women report most of these symptoms more frequently than men throughout their life course, but only vasomotor symptoms and some psychological complaints are clearly temporally associated with perimenopause.
Likewise, researchers combed through health interviews with over 8000 Dutch men and women aged between 25 and 75, and found that women reported each of twelve complaints usually attributed to perimenopause more often than men throughout their lives, but only excessive sweating - clearly related to vasomotor symptoms - increased more in women than in men during the perimenopausal period.
Australian researchers sent a 47-item questionnaire derived from various menopause and 'low testosterone syndrome' symptom rating scales to 46-60 year olds, and found that while, as expected, women experienced substantially more vasomotor symptoms in perimenopause, "both men and women experience similar symptoms, although women are more distressed by them". Rather oddly, the authors interpreted women's greater distress level as "signifying support for a menopausal syndrome in women". But I wonder whether the greater distress levels are better explained by a) the fact that on average, women display higher levels of negative emotionality (called 'neuroticism' in the personality literature) than men, so that they are more likely to be disturbed by symptoms; b) the intensive marketing of the notion of perimenopause as a time of terrible travail in women's lives, so that every minor symptom is seized upon as evidence that one has begun a descent into hell; or c) both of the above.
It's noteworthy that many symptoms ascribed to perimenopause, are also held to be indicative of premenstrual dysphoric disorder, a fake condition that was essentially invented by pharma giant Eli Lilly in order to extend the patent life of its blockbuster antidepressant, Prozac, by rebranding it as 'Sarafem', a supposedly targeted treatment for this invented diagnosis.
In other words, at every stage of women's lives, an enterprising hustler will package up their maladies into a 'syndrome' and then market them a solution. As a writer who interviewed several 'experts' on perimenopause astutely observed,
"I’m noticing that a lot of the symptoms you’ve described sound like what I started experiencing the second I turned 30."
The responses of her 'experts' to this comment were revealing:
"Well, yes: Some perimenopausal symptoms echo general aging symptoms, says [neuroscientist and author of The Menopause Brain, Lisa] Mosconi; the difference is that hormonal changes in perimenopause makes those symptoms more persistent. Some of the life stressors common in one’s 30s (career changes, motherhood, etc.) can also cause hormonal fluctuations, adds [founder of the Harper Clinic and co-author of The Perimenopause Solution, Shahzadi] Harper, but at some point, our estrogen levels begin to diminish and don’t come back up again. (Unless you start hormone therapy — more on that in a minute!)
That said, Mosconi offers a few words of reassurance. 'Not all symptoms are inevitable or severe, and about 10 percent of women don’t report any symptoms other than menstrual irregularities,' she adds. Harper, too, notes that stress and lifestyle factors affect the severity of our perimenopause symptoms. So just … don’t stress."
So let me get this straight: there are symptoms that just indicate you're getting older, but if you get them while you're going through perimenopause (which is, by definition, going to coincide with getting older), then perimenopause-related hormone changes will make these symptoms "more persistent". Wouldn't they become more and more persistent as you got older anyway though, if they are symptoms of aging? And if you got those same symptoms in your 30s, before you entered perimenopause, back then they were due to life stresses, but now those exact same symptoms are caused by perimenopause... but if you are stressed then those symptoms will be worse. So why are they caused by stress which disrupts your hormones when you're in your 30s, but caused by hormonal disruption which is exacerbated by stress in your 40s? Somebody help me out here - I'm confused!
What's caused by perimenopause... and what's not?
The following symptoms and biomarkers of perimenopause have reliably been demonstrated to be linked to the decline in estrogen and progesterone levels that occur as women's ovarian function winds down, and eventually ceases:
Vasomotor symptoms. Hot flushes and night sweats are, as mentioned previously, strongly associated with the altered hormonal milieu of perimenopause, although their exact mechanism is still not fully understood. The majority of women in Western countries - roughly 75 per cent - experience vasomotor symptoms during perimenopause, but a long-term follow-up study of US women found that rates vary between ethnicities: Black women report the highest prevalence, with Hispanic and White women having roughly equal rates, and Chinese and Japanese women having the lowest reporting rates. Across the cohort, smoking, being overweight or obese, having a lower education level, a history of premenstrual symptoms, higher symptom sensitivity at the first follow-up visit, and more baseline anxiety and depressive symptoms, were all predictors of more intense vasomotor symptoms.
Changes in blood lipids and lipoproteins. Regardless of their age at the time of menopause and their ethnicity, women's levels of total cholesterol, low density lipoprotein cholesterol (LDL-C), and apolipoprotein B (which is a specific marker of atherogenesis, or propensity to form atherosclerotic plaque) all increase in the interval from one year before to one year after the final menstrual period, indicating that the rise is driven by hormonal changes, not chronological aging.
High density lipoprotein cholesterol (HDL-C) - formerly considered the 'good cholesterol' that helps to prevent atherosclerosis - also increases over the two years spanning the last menstrual period, but its function declines, making it less protective. Importantly, women with higher estradiol levels during the two years post-menopause have a higher triglyceride content in their HDL, which is linked to greater cardiovascular disease risk. Women considering menopausal hormone therapy (which raises estradiol levels) should bear this in mind.
Critically, there is a direct link between the severity of vasomotor symptoms, and cardiovascular risk factors. Women who report vasomotor symptoms have higher blood pressure and total cholesterol levels, LDL-C, apolipoprotein B and triglycerides. These associations between hot flush and night sweat severity, and an adverse cardiovascular risk profile, were particularly marked in leaner women.
Women who have adopted a low-carbohydrate, animal food-based, high saturated fat diet, take note: this way of eating may help you control your weight (simply by limiting energy intake), but it is highly likely to cause adverse changes in your lipids and lipoproteins, which put you at risk of cardiovascular disease, and it may be increasing your vasomotor symptoms. And since vasomotor symptoms are linked to future risk of hypertension, insulin resistance and diabetes, regardless of obesity, a low-carbohydrate animal-based diet may be the quintessential pyrrhic victory: weight control now, metabolic syndrome later.Vascular changes. Declining estradiol levels are associated with thickening of arterial walls (indicating plaque accumulation), increased arterial stiffness and impaired function of the endothelium - the lining of the artery wall, which helps to regulate blood pressure, blood flow and the 'stickiness' of blood.
Change in body composition. While weight gain per se cannot be attributed to perimenopause, the altered hormonal milieu does lead to an increase in total body fat (i.e. a relative loss of lean tissue), and an increase in abdominal visceral adipose tissue (deep belly fat) and cardiovascular fat (fat deposited around the heart), both of which are linked to the increased rates of coronary heart disease seen in women after menopause.
In the eight years before the final menstrual period, women lose lean (muscle) mass and gain fat mass, resulting in a gradual weight gain averaging roughly 0.5 per cent of one’s body weight per year. This weight gain stabilises about two years after menopause. Visceral adipose tissue begins to accumulate at an accelerated rate two years before the final menstrual period, and continues on the same trajectory for the next five years:
Diminished bone density and toughness. The decline in estradiol levels during the menopausal transition increases bone resorption, leading to rapid bone loss, osteoporosis, and increased risk of fragility fractures.
Vaginal dryness and pain during sex. Declining estrogen levels lead to thinning and drying of the vaginal wall, and changes to the vaginal microbiome, which cause irritation, itching, burning, and discomfort or pain during sex. The prevalence of these symptoms increases across the menopausal transition.
It's not clear whether the following symptoms are caused by perimenopause, or are due to aging, stress, social or personality factors:
Sleep difficulties. Once sleep disturbance due to night sweats is accounted for, the menopause transition in itself doesn't seem strongly related to difficulties with sleep. Women with high anxiety and stress levels are more likely to have sleep problems during perimenopause.
Depression. A review of "12 prospective studies reporting depressive symptoms, major depressive disorder, or both over the menopause transition... found no compelling evidence for a universal increased risk for either condition." Women who have already had depressive episodes are more likely to report high levels of depressive symptoms in the years immediately before their last menstrual period. Women with severe vasomotor symptoms and who experience stressful life events are also more vulnerable to perimenopausal depression. Among women with no history of depression, between 10 and 30 per cent develop severe depressive symptoms before their last menstrual period, dropping rapidly after menopause such that by the second year postmenopause, depressive symptoms were down to just zero to 15 per cent. After menopause, both women with and without a prior history of depression are less likely to have low mood.
A faster rise in FSH (a marker of menopausal status) before the final menstrual period was associated with lower risk of depressive symptoms following the last period, which suggests that a more rapid transition to menopause leads to more stable hormone levels and fewer depressive symptoms; conversely, a long drawn-out perimenopause increases vulnerability to depressive symptoms. Once again, this has implications for menopausal hormone therapy, which slows down the transition to menopause by suppressing FSH.Anxiety, irritability, loss of libido, fatigue. These symptoms commonly cluster together in individuals, but their relationship with perimenopause is unclear and they may be more related to life stage, occupational pressure, or relational issues than to hormonal fluctuations.
These signs and symptoms are not attributable, or probably not attributable to the hormonal milieu of perimenopause, but are more directly attributable to aging and/or poor health and/or psychosocial problems:
Blood pressure, insulin, glucose, Lp(a), and hemostatic and inflammatory factors
Low sexual desire, arousal and emotional satisfaction, aside from that related to vaginal dryness and pain.
Summing up
So that's the deal. Declining hormone levels are definitely responsible for the hallmark symptoms of perimenopause and the postmenopausal phase - vasomotor symptoms and dry vagina - and they also drive unfavourable changes in body composition, blood lipids and vascular function. The relationship between perimenopause and psychological symptoms such as depression, anxiety and sleep difficulties (aside from those induced by vasomotor symptoms) is more tenuous; and most of the somatic symptoms attributed to perimenopause - such as joint aches and dry skin - are caused not by hormonal changes but by aging.
'Perimenopause' bears many of the telltale signs of disease mongering, and it's abundantly clear that pharmaceutical companies and individuals with conflicts of interest see mid-life and older women as a lucrative market for their wares. Women need to protect themselves against the risks of unnecessary treatment by getting informed about this inevitable transition into their third phase of life.
In Part 2, I'll dig into the research on menopausal hormone therapy: what symptoms does it effectively treat, what doesn't it work for, and what are the risks?