1.3 Menopause

Question 1

What does date of menopause mean?

Answer 1

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

Question 2

What does post menopause mean?

Answer 2

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

Question 3

What does menopausal transition mean?

Answer 3

Phase extending from the onset of menopausal symptoms to the final menstrual period (highly variable; average 3 years)

Question 4

What does peri menopause mean?

Answer 4

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

Question 5

What is premature ovarian failure?

Answer 5

Menopause occurring before 40 years of age (premature ovarian insufficiency) → different management from patients with later physiological menopause

Question 6

What is early menopause?

Answer 6

Menopause occurring between 40 – 45 years of age → managed in a similar way to patients with POF

Question 7

what are the hormonal changes associated with menopause?

Answer 7

In the post-menopausal phase, the gonadotrophins are high (FSH > 30 IU/dL), with low oestradiol (< 40 pg/mL) and undetectable progesterone, AMH, inhibin

Question 8

why does inhibin decrease in menopause?

Answer 8

Normally produced by the ovarian granulosa cells → decline in number of ovarian follicles in early menopause transition → reduced inhibin B

Question 9

why does anti mullerian hormone (AMH) decrease in menopause?

Answer 9

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

Question 10

Why does FSH increase in menopause?

Answer 10

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

Question 11

Why does oestrodial decrease in menopause?

Answer 11

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

Question 12

Why does progesterone decrease in menopause?

Answer 12

Falls steadily throughout menopause transition (due to reduced progesterone production by the corpus luteum and increased frequency of anovulation)

Question 13

What oestrogens dominate pre- menopause?

Answer 13

Mainly 17β-oestradiol (E2) → 95% derived from the ovaries (from CYP450 metabolism of oestrone and testosterone)
• Levels vary with the menstrual cycle

Question 14

What oestrogens dominate post - menopause?

Answer 14

Mainly oestrone (E1) → derived from hepatic E2 metabolism and adipose peripheral conversion of androstenedione
• ~1/3 biological potency of E2

Question 15

where is testosterone produced in the body?

Answer 15

Pre-menopausal: 50% produced via peripheral conversion of androstenedione (25% in the ovaries; 25% in adrenal cortex):
• Testosterone aromatised to oestradiol intracellularly

Question 16

Why does testosterone decrease during menopause?

Answer 16

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)

Question 17

how is androstenedione affected during menopause?

Answer 17

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

Question 18

how is Dehydroepiandro-sterone sulfate (DHEAS) affected during menopause?

Answer 18

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)

Question 19

What is the criteria for diagnosis of menopause in woman > 45 years old

Answer 19

Clinical diagnosis: history of menopausal symptoms (see below) + secondary amenorrhoea for ≥ 12 consecutive months
• Menopause transition: based on menopausal symptoms + menstrual irregularity

Question 20

What is the criteria for diagnosis of menopause in woman < 45 years old

Answer 20

Lab testing (if suspected primary ovarian failure or early menopause) → 2 FSH samples taken 4 – 6 weeks apart (raised > 40 pmol/L)

Question 21

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)

Answer 21

brainstem thermoregulatory nucleus;

cigarette smoking, obesity

Question 22

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?

Answer 22

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

Question 23

What are the short term effects of menopause

Answer 23

• Hot flushes
• Urinary urgency & frequency, Vaginal dryness, Dyspareunia
• Menstrual irregularity (due to anovulatory cycles)
• Low mood, Memory loss, Insomnia
• Decreased libido, Dyspareunia

Question 24

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’)

Answer 24

20s – 30s;

BMI , lifestyle (smoking, alcohol), diet , genetics , co existing diseases

Question 25

what is the benefit of weight management?

Answer 25

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

Question 26

what is the benefit of exercise?

Answer 26

Relieves hot flushes, reduces CVD & osteoporosis risk

Question 27

what is the benefit of smoking cessation?

Answer 27

Relieves hot flushes, reduces CVD & osteoporosis risk

Question 28

what is the benefit of avoidance of alcohol & caffeine?

Answer 28

Relieves hot flushes

Question 29

what is the benefit of adequate calcium & vitamin d intake?

Answer 29

Reduces risk of osteoporosis

Question 30

what is the benefit of phytoestrogens?

Answer 30

Relieves hot flushes (some evidence → plant-based oestrogens)
• Isoflavones: soya beans, chickpeas, clover
• Lignans: flax seeds, bran

Question 31

what is the indication of combined (oestrogen + progesterone) therapy?

Answer 31

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

Question 32

what ist he indication of only oestrogen therapy?

Answer 32

Women who have had a hysterectomy (no risk of endometrial cancer)

Question 33

what are the benefits of HRT?

Answer 33

• 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)

Question 34

What are the risks of HRT?

Answer 34

In all women: increased risk of breast cancer and ATEs/VTEs

• In older women > 60 years of age: increased risk of CVD