1.3 Menopause Flashcards
What does date of menopause mean?
Corresponds to the woman’s final menstrual period (only known with certainty after 12 consecutive months of amenorrhoea)
• Normally occurs between 45 – 55 years of age
What does post menopause mean?
Phase of a woman’s reproductive life beginning at the date of the final menstrual period:
• Associated with long-term loss of protective oestrogen effect on urogenital & cardiovascular systems, and bone
What does menopausal transition mean?
Phase extending from the onset of menopausal symptoms to the final menstrual period (highly variable; average 3 years)
What does peri menopause mean?
Phase extending from the onset of menopausal symptoms to 1 year after the final menstrual period:
• Associated with symptoms of variable severity (vasomotor, menstrual, psychological, sexual) → usually self-limiting but may persist in some women
What is premature ovarian failure?
Menopause occurring before 40 years of age (premature ovarian insufficiency) → different management from patients with later physiological menopause
What is early menopause?
Menopause occurring between 40 – 45 years of age → managed in a similar way to patients with POF
what are the hormonal changes associated with menopause?
In the post-menopausal phase, the gonadotrophins are high (FSH > 30 IU/dL), with low oestradiol (< 40 pg/mL) and undetectable progesterone, AMH, inhibin
why does inhibin decrease in menopause?
Normally produced by the ovarian granulosa cells → decline in number of ovarian follicles in early menopause transition → reduced inhibin B
why does anti mullerian hormone (AMH) decrease in menopause?
Glycoprotein produced by antral (secondary) follicles → not directly involved in feedback mechanisms:
• Levels are high at menarche then decline thereafter as the number of ovarian follicles declines with age
Why does FSH increase in menopause?
Normally inhibited by inhibin B (negative feedback) → low inhibin B fails to suppress FSH → higher FSH in the early follicular phase of the menstrual cycle in the 2 years leading up to final menstrual period
• Persistently elevated during the post-menopause
Why does oestrodial decrease in menopause?
Normally produced by ovarian granulosa cells (in response to FSH) → levels fall in the 2 years leading up to final menstrual period (with some fluctuation):
• Persistently declining during the post-menopause
Why does progesterone decrease in menopause?
Falls steadily throughout menopause transition (due to reduced progesterone production by the corpus luteum and increased frequency of anovulation)
What oestrogens dominate pre- menopause?
Mainly 17β-oestradiol (E2) → 95% derived from the ovaries (from CYP450 metabolism of oestrone and testosterone)
• Levels vary with the menstrual cycle
What oestrogens dominate post - menopause?
Mainly oestrone (E1) → derived from hepatic E2 metabolism and adipose peripheral conversion of androstenedione • ~1/3 biological potency of E2
where is testosterone produced in the body?
Pre-menopausal: 50% produced via peripheral conversion of androstenedione (25% in the ovaries; 25% in adrenal cortex):
• Testosterone aromatised to oestradiol intracellularly
Why does testosterone decrease during menopause?
oss of ovarian follicular function knocks out 25% of peripherally produced testosterone (which is quite difficult for the body to compensate using the adrenal cortex) → levels decline (but not as much as oestradiol → 95% from ovaries)
how is androstenedione affected during menopause?
post-menopausal ovary still contributes 20% to the circulating androstenedione levels → loss of ovarian function is also compensated by increased adrenal synthesis (even in POF) → levels remain largely unchanged
how is Dehydroepiandro-sterone sulfate (DHEAS) affected during menopause?
Pre-menopausal: produced almost exclusively by the adrenal cortex → levels tend to decline with age (both sexes; women > men due to relative oestrogen deprivation)
Menopause: ovaries do not contribute much to DHEAS synthesis in the first place → levels remain largely unchanged from before menopause (only age-related decline)
What is the criteria for diagnosis of menopause in woman > 45 years old
Clinical diagnosis: history of menopausal symptoms (see below) + secondary amenorrhoea for ≥ 12 consecutive months
• Menopause transition: based on menopausal symptoms + menstrual irregularity
What is the criteria for diagnosis of menopause in woman < 45 years old
Lab testing (if suspected primary ovarian failure or early menopause) → 2 FSH samples taken 4 – 6 weeks apart (raised > 40 pmol/L)
Hot flushes are the earliest and most characteristic symptom of oestrogen deficiency:
• Relative (not absolute) decline in oestradiol → dysfunction of _______________ (maintains core temperature)
• Frequency: affects ~75% of women (may be less frequent in Asian women) → generally resolves in < 5 years (persists in 25% of women)
• Risk factors: ______, __________
• Clinical features: subjective sensation of intense warmth of the upper body (lasting 3 – 10 minutes) of variable frequency and intensity (occasional/daily/hourly)
brainstem thermoregulatory nucleus;
cigarette smoking, obesity
Urogenital symptoms are correlated with _____________ :
• Oestrogen receptors in the urogenital system and pelvic region (vagina, vulva, pelvic floor, endopelvic fascia, urethra, bladder trigone) decline with menopause transition → may become restored with oestrogen treatment
• Symptoms are often chronic (rarely resolve spontaneously) → progress if untreated
What are the symptoms?
low oestrogen levels;
Genital: Vaginal dryness, burning, irritation
Pain during intercourse (dyspareunia) → due to vaginal thinning, decreased distensibility, reduced secretions
Urinary: Urgency, dysuria
Recurrent UTIs → due to thinning of vaginal epithelium, change in vaginal pH, reduced secretions
What are the short term effects of menopause
- Hot flushes
- Urinary urgency & frequency, Vaginal dryness, Dyspareunia
- Menstrual irregularity (due to anovulatory cycles)
- Low mood, Memory loss, Insomnia
- Decreased libido, Dyspareunia
What are the effects of menopause o \n bone?
menopause causes bone disorders like osteoporosis:
• Bone density peaks in the __________ and remains constant until perimenopause → rapid decline in late perimenopause and early post-menopause (due to accelerated bone resorption) → loss of 2% (in the spine) and 1% (in the hip)
• Mechanism is unclear → bone cells express oestrogen receptors → oestrogen deficiency appears to stimulate osteoclast formation and activity → resorption
Osteoporosis: important long term consequence of menopause, 1/3 of women have it by 50 years of age –> age adjusted rates of hip fracture ↑ 5 fold since 1960s)
- Decreased bone density –> increased risk of osteoporotic fractures
- Risk factors: low _____________________
- Generally asymptomatic until a fracture occurs (‘silent’)
20s – 30s;
BMI , lifestyle (smoking, alcohol), diet , genetics , co existing diseases
what is the benefit of weight management?
Target is to maintain a normal BMI (not too high/low):
• High BMI: more severe hot flushes, increased CVD risk
• Low BMI: increased osteoporosis risk
what is the benefit of exercise?
Relieves hot flushes, reduces CVD & osteoporosis risk
what is the benefit of smoking cessation?
Relieves hot flushes, reduces CVD & osteoporosis risk
what is the benefit of avoidance of alcohol & caffeine?
Relieves hot flushes
what is the benefit of adequate calcium & vitamin d intake?
Reduces risk of osteoporosis
what is the benefit of phytoestrogens?
Relieves hot flushes (some evidence → plant-based oestrogens)
• Isoflavones: soya beans, chickpeas, clover
• Lignans: flax seeds, bran
what is the indication of combined (oestrogen + progesterone) therapy?
All women > 45 years of age considering HRT as treatment (due to risk of endometrial hyperplasia and cancer in oestrogen-only preparations) → combined HRT not associated with adverse endometrial effects
• Progesterone is mandatory for > 10 days/month
what ist he indication of only oestrogen therapy?
Women who have had a hysterectomy (no risk of endometrial cancer)
what are the benefits of HRT?
- Short-term relief of symptoms of oestrogen deficiency (e.g. vasomotor, low mood, low libido, vaginal dryness) → prolongs euhormonal state of mid-life phase to maintain the endocrine autonomous equilibrium
- Long-term benefit on bone density (if oestrogen deficiency is the only cause of bone complications) → helps to prevent osteoporosis
- Improves the quality of life (psychological + physical) in the long run
*HRT prescribed to women < 60 years of age has favourable benefit/risk profile → older women often also have age-related co-morbidities of the CVS and bone, so they may not necessarily respond well to HRT (+ additional risks of HRT like cancer, increased CVS risk)
What are the risks of HRT?
In all women: increased risk of breast cancer and ATEs/VTEs
• In older women > 60 years of age: increased risk of CVD
