Menopause Flashcards
What is menopause
WHO defines natural menopause as at least 12 consecutive months of amenorrhea not due to physiological/pathological causes. It’s a natural event reached upon exhaustion of primordial follicles
The global age at menopause is on average 51 years (range 40-60 years) suggesting a distinct genetic control; with a strong correlation exists between mothers and daughters
Menopausal health aspects include bone density, breast, the cardiovascular system, mood/cognitive function and sexual well being
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
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
Effective health care support should be individually tailored to all aspects of the menopause when women feel particularly vulnerable
Ageing on follicles
At birth the ovary contains about 500,000-1million primordial follicles
Estimated that for 95% of women by 30yrs only 12% of max. pre-birth NGF population is present and by 40yrs only 3% remains.
The ovarian reserve will determine the rate of decline of NGF & age of the menopause
The initial ovarian pool of NGFs will determine how quickly they become
The ovarian reserve will determine the onset of subfertility to sterility and to complete loss of menstrual cycles – the menopause
List the factors affecting ovarian reserve
Genetics Autoimmunity Ethnicity Nutrition Androgens/PCOS In utero environment
Describe the relationship between AMH and the ovarian reserve
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
After this, the graph is n shaped, with age and AMH, with the peak at around 20 years
Declining levels of AMH with age
AMH secretion from growing follicles
What happens to levels of Inhibin B and FSH as approach peri-menopause?
Link between AFC, AMH, Inhibin B and FSH
Can AMH predict ovarian reserve?
Relation between age-specific anti-Müllerian hormone (AMH) concentrations and the distribution of age at menopause. The left nomogram depicts the baseline AMH levels of 185 normo-ovulatory women and percentile declines. The right nomogram depicts the variation of age at menopause during approximately 11 years of follow up for different AMH percentiles
Are AMH levels a good standard for estimating ovarian reserve
Measurements of AMH and AFC are used to diagnosed premature ovarian failure/insufficiency – but NICE recommendations NOT to use single blood test of AMH for diagnosis of POI
Primary and secondary follicles produce AMH
small antral and antral follicles produce Inhibin B
FSH stimulates secondary, small antral follicles and antral follicles
LH stimulates antral and ovulatory follicles
Antral follicles produce oestrogen
Describe the hormonal changes during menopause
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
List some menopausal symptoms
Hot flashes and night sweats Vaginal dryness Sleep disturbance Mood symptoms Urinary symptoms
Incidence increases from pre-menopause to peri menopause and decreases post menopause
Hot flushes and night sweats
Experienced by approximately 80% menopausal women, can last up to 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 also be caused by several drugs, the carcinoid syndrome, phaeochromocytomas (rare tumour of adrenals) and mastocytosis (accumulation of mast cells in tissues including the skin) – differential diagnosis
Osteoporosis in menopause
Women can lose up to 20% of their bone density in the 5 to 7 years after the menopause (www.nhs.uk).
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
Genitourinary syndrome of menopause (GSM)
GSM → relatively new term for the condition previously known as vulvovaginal atrophy, atrophic vaginitis, or urogenital atrophy
Chronic, progressive, vulvovaginal, sexual, and lower urinary tract condition characterized by a broad spectrum of signs and symptoms
Most of these symptoms attributed to the lack of oestrogen.
These can have a great impact on the quality of life & treatment aimed at symptomatic relief
Describe premature ovarian failure/insufficiency
Defined as cessation of ovarian function before 40 years
Affects 1:100 women before 40 years of age and 1:1000 women before 30 years of age
Reasons include: Genetic Gonadal dysgenesis autoimmune idiopathic viral infections vaccinations congenital enzymatic deficiencies
Features of POF
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
Symptoms and treatment of POF
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
Treatment:
Treatment:
HRT
Combined oral contraceptive pill (but contain higher doses of steroids)
Long term effects of menopause:
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
Treatment of menopausal symptoms
Menopausal hormone replacement therapy (MRT)
Tablets, skin patches, gels and implants to replace oestrogen
Vaginal oestrogen creams/lubricants/moisturisers
New non-oestrogen treatment for GSM
CBT
To help with low mood and anxiety
Regular exercise and good diet
To maintain bone strength and reduce weight and hence risk of various pathologies
Natural/alternative therapies
Bisphosphonates for bone density
Neurokinin B (NKB) antagonists in Phase 2 clinical trials
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
Describe 3 menopausal studies
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 years.
http://www.millionwomenstudy.org/introduction/
Increased risk of breast cancer with HRT – but risk was very dependent on which type of HRT used and when it was started making it complex to dissect out the true impact
