Menopause

Question 1

Define menopause (2)

Answer 1

Natural menopause as at least 12 consecutive months of amenorrhea not due to physiological/pathological causes.

Natural event reached upon exhaustion of primordial follicles

Question 2

Menopause background : (3)

Answer 2

The global age at menopause is on average 51 years (range 40- 60 years) suggesting a distinct genetic control; strong correlation exists between mothers and daughters

Menopausal health aspects include bone density, breast, the cardiovascular system, mood/cognitive function and sexual wellbeing

Effective health care support should be individually tailored to all aspects of the menopause when women feel particularly vulnerable

Question 3

Menopause symptoms (10)

Answer 3

Common symptoms include:
* Hot flushes, night sweats, vaginal dryness and discomfort during sex,
difficulty sleeping, low mood/anxiety, reduced libido
* Physical and emotional changes strongly affect women
* 1:10 women experience suicidal thoughts due to the perimenopause

Question 4

Ovarian reserve - explained (3)

Answer 4

max. no. of follicles in our lifetime -ovarian reserve will determine the onset of subfertility to sterility and to complete loss of menstrual cycles – the menopause

Estimated that for 95% of women by 30yrs only 12% of max. pre-birth NGF population is present
and
by 40yrs only 3% remains.

Question 5

Various factors affecting ovarian reserve (7)

Answer 5

genetics
autoimmunity
Ethnicity/geography
Androgens/PCOS
Nutrition
In-utero
abnormalities, medications, drugs

Question 6

AMH marker for ovarian reserve? (2)

Answer 6

The levels of AMH in the human circulation vary during the life cycle, with a sexually dimorphic pattern. Females produce virtually no AMH in utero

Declining levels of AMH with age, AMH secretion from growing follicles

Question 7

What happens to levels of Inhibin B and FSH as approach peri-menopause? (2)

Answer 7

rise in FSH: loss of -tve feedback
dec. in InhibinB: decrease in follicles

Question 8

Can only AMH predict ovarian reserve? (3)

Answer 8

no - it is a good indication of function + potential marker of ovarian reserve + menopause

but w/ Measurements of AMH, AFC, InhibinB + FSH are used to diagnosed premature ovarian failure/insufficiency, predict menopause + prediction of ovarian response in IVF

Question 9

Hormonal changes during the menopause (6)

Answer 9

Ovarian senescence begins around 35 years ends with menopause ~51 years.

Decline in ovarian oestrogen largely related to number of primordial follicles, number of recruitable follicles in each ovarian cycle and proportion of follicles that reach adequate maturity

Rise in FSH – loss of negative feed back

Decline in inhibin B and AMH

Decline in androgen synthesis in adrenal glands and ovaries

Marked decline in fertility after age of 35 although this depends on ovarian reserve

Question 10

What symptoms are related to the drop of estrogen? (7)

Answer 10

Climacteric compounds - hot flushes etc. DRAMATIC

normal lag:
vaginal wall atrophy, incontinence, Skin atrophy, Stress incontinence, oesteoporosis, athersclerosis

Question 11

How are the symptoms recorded and thus…? (2)

Answer 11

self-reported = bias

= a big spread in data of when and what is experienced

Question 12

Hot flushes and night sweats (6)

Answer 12

approximately 80% menopausal women ( 5-13 years though number of episodes decrease with time

Measuring frequency = most objective way of assessing severity of menopausal symptoms

Typically occurs on the face but can occur in other body areas such as arms and the torso

Aetiology unknown:: but oestrogen interacts with the noradrenergic system in the brain which plays a major role in thermogenesis. Other neural systems have also been implicated such as the endorphin pathways

Wet’ flushing occurs through inappropriate vasodilation and activation of sweat glands through both central and peripheral mechanisms. Hormone withdrawal and emotions are both causes

Dry’ flushing (no sweat!) can be caused by several drugs, the carcinoid syndrome, phaeochromocytomas (rare cancer of adrenal medulla) &
mastocytosis (accumulation of mast cells in tissues including the skin)

Question 13

Osteoporosis in Menopause (4)

Answer 13

Can lose up to 20% of their bone density in the 5 to 7 years after the menopause

The drop in bone density is caused by falling levels oestrogen, which impairs the normal cycle of bone remodelling
i.e. increases amount of bone resorbed (osteoclastic activity) over the amount deposited (osteoblastic activity), leading to net loss of bone

Although bone density decreases at the menopause, the risk of osteoporosis and fractures stays relatively low until women get much older, because bone density is only one of the things that affects bone strength.

Treatment option include the use of bisphosphonate compounds, maintaining calcium and Vit.D levels, weight-bearing exercises

Question 14

Genitourinary Syndrome of Menopause (GSM) (4)

Answer 14

Previously known as vulvovaginal atrophy, atrophic vaginitis or urogenital atrophy.

Chronic, progressive, vulvovaginal, sexual and lower urinary tract condition characterised by a broad spectrum of signs and symptoms

GSM more accurately describes the post-menopausal hypoestrogenic state of the genitourinary tract.

Can have a significant impact on quality of life

Treatment aimed at symptomatic relief.
 GSM for BSSM

Question 15

Premature ovarian failure (POF)/insufficiency (POI) definition

Answer 15

Defined as cessation of ovarian function before 40 years

Question 16

Various causes of premature ovarian failure/insufficiency (9)

Answer 16

Genetic
Gonadal dysgenesis
Autoimmune anti-ovarian antibodies
Congenital enzymatic deficiencies (e.g. galactosemia)
Vaccination
Anti-HPV
Oncologic treatment
Viral infections e.g. mumps
UNKNOWN(idiopathic) : Up to 50% of all cases

Question 17

Investigating POF (5)

Answer 17

will presnt w/ Hypergonadotrophic-hypogonadism:
Low estradiol (<20 IU/l)
Elevated FSH (>20 IU/l)
Low AMH levels (< 0.5 ng/ml)
Low inhibin B levels

Assessed day 3 of the menstrual cycle

Question 18

Symptoms of POF (2)

Answer 18

Symptoms are those similar to those observed at a normal menopause. - - - Loss of oestrogen

e.g. oligomenorrrhea, hot flushes, sweating, nervousness, skin
changes, mucous membrane dryness  decreased bone mineral
density (osteoporosis), metabolic changes, CVD, urogenital atrophy
and early mortality

Question 19

treatment of POF (2)

Answer 19

 HRT - to prevent CVD/ death etc.
 Combined oral contraceptive pill (but contain higher doses of steroids)

Question 20

Long term consequences and treatment of premature menopause (5)

Answer 20

 Adverse effects on health and mortality
 HRT can lessen some of these risks but not all
 Provide HRT at least until natural age of menopause
 Psychological aspects of early menopause
 Individualising treatment both in terms of HRT and the psychological impact

Question 21

Treatment of menopausal symptoms (5)

Answer 21

 Menopausal hormone therapy (MHT/HRT)
- Tablets, skin patches, gels and implants to replace oestrogen
- Vaginal oestrogen creams/lubricants/moisturisers

 Plant-based, bioidentical hormones
- unregulated & no evidence of effectiveness

 CBT plus relaxation techniques
- To help with low mood and anxiety

 For treatment of hot flushes
- NKB hypothalamic neuropeptide involved in GnRH secretion and thought to stimulate activity of the vasomotor centre, resulting in hot flushes

 Non-Hormonal prescription medications (but not as useful as MHT)
- e.g SSRI (selective serotonin reuptake inhibitors)
- Bisphosphonates for bone density
= Regular exercise and good diet
- To maintain bone strength and reduce weight and hence risk of various pathologies

Question 22

Why should HRT always be monitored + tweaked? (2)

Answer 22

Unopposed oestrogens cause proliferation of the endometrium – endometrial cancer

Different preparations of oestrogen and progesterone used for HRT and different routes of administration

Question 23

Bad press HRT - 3 large studies – 1990’s to early 2000’s (3)

Answer 23

Heart and Estrogen/Progestin Replacement Study (HERS)
(CCEPT in postmenopausal women with CHD)
- HERS ended after 4.1 years due to risks
- Women’s Health Initiative (WHI) (healthy postmenopausal women)

 Prospective, randomised, double-blind, placebo-controlled studies of continuous- combined estrogen progestin therapy (CCEPT) or CEE only
- Evaluated only one hormone combination; no perimenopausal women
- WHI was stopped at 5.2 years –increased risk of breast cancer

 Million women study – started recruiting participants in 1996 to investigate effect of use of HRT amongst other things.
- Study includes 1 in 4 women in UK born between 1935 and 1950
- Participants sent postal resurvey questionnaires every 3-5 year

Question 24

The tides began to change again when data from the studies were re-evaluated and analysed (3)

Answer 24

Subsequent re-examination of the data from the WHI and Million Women study showed certain flaws in interpretation and study designs and that risks of the WHI study were not statistically significant apart from
venous thrombosis and ischaemic stroke

The follow up from the WHI trials showed benefits for the use of MHT in younger women (50-59 years) have decreased coronary disease and all causes of mortality

The tides began to change again when data from the studies were re-evaluated and analysed NICE recommends its use for menopausal symptoms!

Question 25

Menopause and Society (3)

Answer 25

Ageing is often associated by women with a loss of status – feeling of becoming invisible

Closely associated with psychosocial events in midlife and ageing i.e. health issues, family and marital relations, sociocultural back ground and attitudes toward a sex life determine women’s experience of the menopause

Campaigning by women resulted in recent publication (Oct.2022) of all-party parliamentary group on menopause report. Five key recommendations:
1. Funding research into benefits of HRT
2. Ensuring doctors are trained
3. Scrapping prescription charges for HRT in England
4. National drug formulary for HRT
5. Summoning all women aged 45 to GP to discuss menopause