15.10 — Menopause and Male Ageing

Menopause is not a hormone deficiency that develops. It is the ovaries running out of the material they work on (Chapter 15.4), and it happens at roughly the same age in every population studied — around 51 — with remarkably little variation.

Male reproductive ageing is a different process entirely: gradual, incomplete, and never reaching an end point. Men in their eighties can father children.

Chapter 12.6 covered the endocrinology. This chapter covers the experience, the management and what is worth acting on.

Menopause: the stages

Premenopause — normal cycles.

Perimenopause — the transition, typically 4 to 8 years, beginning on average in the mid-forties.

And this is where most symptoms occur, which surprises people who expect them to start after periods stop.

The reason is that perimenopausal hormone levels are not low — they are erratic. Follicles become less responsive, so FSH rises to compensate; the follicles that do respond may produce a surge of oestrogen far above normal.

So the levels swing unpredictably, and it is the fluctuation rather than the deficiency that produces the symptoms.

Which has a direct practical consequence: blood tests are largely unhelpful in diagnosing perimenopause, because a level taken on any given day reflects that day. The diagnosis is clinical, from the symptoms and the age, and requesting hormone tests in a woman over 45 with typical symptoms is explicitly not recommended.

Menopause — defined retrospectively, after 12 consecutive months without a period.

Postmenopause — everything after.

Symptoms

Around 75 percent experience hot flushes, and the mechanism is in Chapter 12.6: oestrogen withdrawal narrows the hypothalamic thermoneutral zone, so a small rise in core temperature triggers a full heat-loss response.

Typical duration is 7 to 10 years — considerably longer than the "couple of years" people are often told — and around 10 percent have them for more than a decade.

Night sweats disrupt sleep, and much of the fatigue, irritability and difficulty concentrating attributed directly to hormones is substantially downstream of broken sleep.

Sleep disturbance, from night sweats and independently.

Mood changes — and the relationship is genuine rather than incidental. Perimenopause carries an increased risk of depression, particularly in women with a history of it or of premenstrual dysphoric disorder — the pattern suggests sensitivity to hormonal change rather than to any particular level.

Cognitive symptoms — "brain fog", word-finding difficulty, poorer verbal memory. Measurable in studies, generally modest, and largely recovering after the transition. It is not early dementia, and saying so relieves a common and specific fear.

Joint aches — extremely common and rarely mentioned in the standard list, which means women frequently do not connect them.

Palpitations, headaches, skin and hair changes.

And the genitourinary syndrome of menopause, which behaves differently from all of the above.

Vaginal dryness, discomfort, pain with sex, urinary frequency, urgency and recurrent urinary infection (Chapter 15.3).

These do not resolve with time. They progress. Which is the single most important asymmetry in this chapter: hot flushes eventually stop, and urogenital symptoms get worse without treatment.

And they are substantially under-reported — surveys consistently find that a minority of affected women raise them, and a minority of clinicians ask.

Treatment

Chapter 12.6 gave the evidence on hormone replacement therapy and the history of the 2002 reversal. The practical points:

For most women under 60, or within 10 years of menopause, with troublesome symptoms, the benefits outweigh the risks.

Transdermal oestrogen — patch, gel or spray — avoids the increased clot risk of oral preparations, because it bypasses the liver's first pass (Chapter 7.5). It is preferred in women with clot risk factors, migraine, obesity or gallbladder disease.

Progestogen is required in any woman with a uterus, because unopposed oestrogen causes endometrial hyperplasia and cancer. Micronised progesterone appears to carry a lower breast cancer risk than older synthetic progestogens, and the hormonal intrauterine system can provide it while also managing heavy bleeding.

Vaginal oestrogen is a separate decision from systemic HRT. Very low dose, minimally absorbed, effective for urogenital symptoms, and safe for essentially everyone — including most women who cannot take systemic hormones, and, with specialist input, many breast cancer survivors.

It is one of the most under-prescribed effective treatments in medicine, and the reason is that the symptoms are not raised.

Testosterone has good evidence for low sexual desire in postmenopausal women that is causing distress, once other causes are addressed. It is not licensed for women in many countries, which is a regulatory rather than an evidential position.

Non-hormonal options for those who cannot or prefer not to take HRT: SSRIs and SNRIs reduce hot flushes; gabapentin; clonidine; and the new NK3 receptor antagonists, which target the specific hypothalamic neurons involved and are the first genuinely new class in decades (Chapter 12.6).

Cognitive behavioural therapy has good evidence for hot flushes, which surprises people — it does not reduce the physiological event but substantially reduces the distress and interference.

What has poor evidence: most herbal preparations, including black cohosh and evening primrose oil; and "bioidentical" compounded hormones, which are marketed as safer and are unregulated, not tested, and inconsistently dosed. Regulated body-identical preparations — micronised progesterone and oestradiol — are a different thing and are what is meant clinically.

The long-term consequences

And these matter more than the symptoms, because they are silent.

Bone. Loss accelerates to 2 to 3 percent a year for the first 5 to 10 years (Chapter 5.9). This single effect is why osteoporosis is so much commoner in women, and it is why menopause is the point at which bone health should be considered rather than at the first fracture.

Cardiovascular. Risk rises after menopause and the gap with men narrows. HRT started early appears to be neutral or beneficial for cardiovascular risk; started more than 10 years after menopause it is not — the "timing hypothesis", and it is the main reason the trial results were so misleading when applied to younger women.

Urogenital, as above.

Metabolic — body fat redistributes toward the abdomen, and insulin sensitivity falls modestly.

Premature ovarian insufficiency

Menopause before 40, affecting around 1 percent of women.

Causes: genetic — including Turner syndrome and fragile X premutation carriers, autoimmune, chemotherapy or radiotherapy, surgery, and frequently unknown.

And the management differs from natural menopause in one important respect. HRT is not optional but recommended until at least the average age of menopause, because decades of oestrogen deficiency carry substantial bone and cardiovascular consequences.

The doses used are typically higher than for menopausal symptom control, because the aim is to replace what would physiologically be present.

And fertility is not always zero. Around 5 to 10 percent of women with premature ovarian insufficiency conceive spontaneously, which is worth knowing in both directions — for hope and for contraception.

Surgical menopause

Removal of both ovaries produces immediate menopause, with an abrupt rather than gradual hormone fall.

Symptoms are typically more severe and more sudden, and the long-term consequences of losing oestrogen years earlier than natural are substantial.

Which is why ovarian conservation is preferred at hysterectomy where there is no reason to remove them, and why HRT is strongly recommended after surgical menopause in younger women.

Male reproductive ageing

Testosterone falls by around 1 percent a year after about 30 to 40 (Chapter 12.6).

And "male menopause" is a misleading term, because there is no equivalent cessation. Sperm production continues; testosterone declines gradually and never stops; and many men in their eighties have levels within the young adult range.

What does change:

Erectile function — slower to develop, less firm, longer refractory period (Chapter 15.5).

Libido declines modestly on average, with enormous individual variation.

Semen parameters decline slowly, and fertility persists.

Muscle mass and bone density decline, partly from testosterone and partly from reduced activity.

Prostate enlarges (Chapter 10.5).

And paternal age has effects worth stating. The rate of new mutations rises with paternal age (Chapter 2.5) — roughly 25 new mutations from a 20-year-old father and 65 from a 40-year-old. This translates into modestly increased risks of achondroplasia, some other dominant conditions, and — with much weaker and more contested evidence — autism and schizophrenia.

The absolute risks remain small, and the point is that the traditional framing of maternal age as the only concern is incomplete.

Late-onset hypogonadism

Genuine testosterone deficiency with symptoms, and it is worth diagnosing properly because it is both over- and under-treated.

Diagnosis requires both consistent symptoms and consistently low measured testosterone, on at least two morning samples — because levels follow a daily rhythm and an afternoon sample is uninterpretable.

And a large proportion of low testosterone is secondary to something else that is more worth treating. Obesity — fat converts testosterone to oestrogen, and weight loss raises it measurably. Sleep apnoea. Depression. Alcohol. Opioids. Chronic illness.

Treating those raises testosterone without any hormone at all, and it treats the actual problem.

Where replacement is genuinely indicated it works well — improving libido, mood, muscle mass and bone density.

The risks are real: raised red cell count with thrombosis risk, worsening sleep apnoea, prostate stimulation, and suppression of the axis, which shrinks the testes and stops sperm production (Chapter 15.2).

And that last point is the one most often not explained. A man taking testosterone for symptoms while hoping to father a child is working against himself, and the recovery after stopping takes 6 to 18 months.

Testosterone clinics selling treatment on the basis of vague symptoms and a single low-normal reading are a genuine problem, and the distinction between treating a deficiency and selling a hormone is worth insisting on.

What ends well

A short closing note, because this chapter otherwise reads as a list of declines.

Sexual activity in later life is far commoner than younger people assume, and satisfaction frequently rises rather than falls — surveys consistently find that older adults report better sexual satisfaction despite reduced frequency and more physical difficulty.

Most of the physical changes are manageable, and the barriers are more often lack of information and reluctance to ask than any physiological limit.

And the health interventions that matter in this period are the same ones that matter for everything else: physical activity, which preserves bone, muscle, vascular and sexual function simultaneously; not smoking; managing blood pressure; and sleep.

The reproductive system stops being a reproductive system and continues being an endocrine one, and looking after it is largely looking after everything else.

What the next page fixes

Chapter 15.11 covers contraception — every method, how each works, how well each works in practice rather than in theory, and how to choose between them.