Menopause Flashcards
Describe the various definitions associated with menopause
- Definition: The permanent cessation of menstruation resulting from the loss of ovarian follicular activity.
- Natural menopause is recognized after 12 consecutive months of amenorrhea, with no other obvious pathological or physiological cause.
- Median Age: ~51 years
- Menopause is a retrospective clinical diagnosis (World Health Organisation 1994)
Extra notes:
* Surgical menopause: removal of both ovaries (any age)
* Premature ovarian insufficiency (PO): cessation of ovarian function before age of 40 (↑ risk of CVD, dementia and osteoporosis)
* Permanent loss of ovarian follicular developement
* Loss of cyclical production of estradiol, progesterone and testosterone - may/may not result in symptoms
Describe the primordial follicles
- Fundamental reproductive units of the ovary.
- Pool of non-growing follicles from which all dominant preovulatory follicles are selected.
- Formed between 6-9 months of gestation.
- Only 400 will develop and undergo ovulation/corpus luteum formation; others die by atresia.
- Continued decline in number - by menopause, primordial follicles are difficult to find.
Describe the endocrinology of menopause
- Normal: pulsatile release of GnRH from hypothalamus → anterior pituitary → gonadotrophins (FSH/LH) → stimulate ovary to produce sex steroids (oestrogen, progesterone, testosterone) and peptides (inhibin A and B) →
feedback to hypothalamus
Menopause: complex feedback that fluctuates and changes
- Progressive decline in follicle numbers, inhibin B.
- Progressive rise in FSH
- Increased FSH maintains or increases estradiol and inhibin A secretion.
- Late fall in Estradiol (E2), inhibin A.
- Pre-menopausal fall in testosterone, but maintenance across menopausal transition.
- Loss of ovarian estrogen, progesterone, and testosterone production.
- After menopause: Adipose tissue produces some estrogen from adrenal steroid precursors.
Anti-Müllerian Hormone (AMH)
- AMH is the product of growing ovarian follicles and the principal regulator of early follicular recruitment.
- Concentration of AMH in blood may reflect the non-growing follicle population (ovarian reserve).
- AMH concentrations are relatively stable across the menstrual cycle but decline with age.
- Low levels indicate diminished ovarian reserve and predict approaching menopause.
List the early signs of menopausal transition
- Perimenopause/Menopausal Transition describes time from the onset of cycle irregularity through until 12 months after the LMP
- involves irregular menses, lighter menses, symptoms of estrogen insufficiency, and symptoms of estrogen excess.
- Hormone level fluctuations during the transition.
Describe how one might predict menopause
- Age between 45-55
- Average age 51.5 (10% pre-45)
- Various methods for predicting menopause include age, antral follicle count (AFC), ovarian volume, FSH, inhibin B, anti-Mullerian hormone, ovarian biopsyin extremem cases, and dynamic testing (Dynamic testing (clomiphene citrate to stimulate ovary and see if there is any activity, gonadotrophin)
- The menopause is usually a clinical diagnosis, and blood tests are usually not required.
- None of the tests alone or together will accurately predict menopause.
Describe factors determing earlier and later age of menopause
Earlier Age of Menopause:
- Familial and genetic factors (e.g., ER-α polymorphism)
- Cigarette smoking – by ~2 years
- Oophorectomy, e.g., for endometriosis, cancer; i.e. iatrogenic menopause
- Chemotherapy, radiation
- Hysterectomy (up to 4 years advancement)
Later Age of Menopause:
- Later age at menarche
- Longer menstrual cycle length
- Oral contraceptive use (insufficient evidence)
- Parity (slim margin)
Describe diffrences in onset and symptoms of menopause among ethnic group
- Same Age at Menopause: Asian + Caucasian women
-
Earlier Menopause:
- African-American / Latina women / Filipino / Malay women in developed countries
- Developing countries
- Rural women
- High altitudes
-
Symptoms:
- Higher Frequency: African-American + Hispanic – vaginal dryness
- Lower Frequency: Asian women (less flushes and more joint pain)
Describe premature ovarian insufficiency
- Cessation of ovarian function 2 standard deviations prior to the population mean age of menopause.
- i.e., 2 X SD prior to 51.5 years
- Practical definition: Before the age of 40 years
Causes of Premature Ovarian Insufficiency
- Genetic/cytogenetic
- Fragile X syndrome
- Enzymatic defects
- Immune disturbances
- Defects in gonadotropin structure or actions
- Physical insults
- Ionizing radiation/Chemotherapy
- Surgery
- Viral infection
- Cigarette smoking
- Idiopathic – most common
Describe the clinical consequences of menopause
- Attributed to the loss of ovarian estrogen production.
- Following menopause, adipose tissue continues to produce some oestrogen
- Overweight women go on producing oestrogen (more at risk of endometrial cancer
- Following menopause, adipose tissue continues to produce some oestrogen
- Debilitating symptoms do not correlate with estrogen levels.
- Tissue estrogen insufficiency contributes to the pathophysiology of:
- Central fat distribution
- Insulin resistance
- Cardiovascular disease risk
- Osteoporosis
- Cognitive dysfunction (debatablem thought to be identified post-menopause)
List the symptoms of menopause by category
Symptoms Associated with Menopause
- Central: Hot flushes, night sweats, insomnia, mood & memory changes
- Joints and muscles: Aches and pains, osteoarthritis
- Skin: Dryness, thinning, loss of elasticity, formication, acne
- Oral: Reduced saliva, increased gingivitis, changing taste
- Hair: Increased facial hair, thinning scalp and pubic hair
- Vulva and vagina: Dryness, thinning labia, dyspareunia, vulval eczema and skin conditions
- Bladder: Increased urinary urgency, frequency, incontinence, and urinary tract infections
- Long Term: Cardiovascular and skeletal
Describe hot flushes
Vasomotor Symptoms and Alterations in Thermoregulation
- Narrowing of the thermoneutral zone leading to sweating (heat dissipation) or shivering (heat generation).
- Changes in peripheral vascular reactivity.
- Loss of estrogen-mediated vasomotor regulation in CNS.
Why? Because oestrogen modulates thermoregulation in reproductive age. Nerves get ‘used’ to oestrogen, when estrogen drops, thermoregulation is disrupted because of over-firing of nerves in the thermoregulatory centre.
- Hot Flushes (UK)/Flashes (US):
- Warming sensation to intense heat
- Reddening of the skin
- Perspiration
- Palpitations and anxiety
- Not possible to predict whether an individual woman will experience hot flushes
-
Night Sweats:
- Drenching perspiration
- Usually associated with sleep disruption
Side notes:
- estrogen withdrawal exaggerates vasomotor symptoms in menopause
- but does not explain the etiology entriely:
- Vasomotor symptom severity does not correlate with plasma, urinary, or vaginal levels of estrogens.
- Plasma levels between asymptomatic and symptomatic women not different.
- Hot flushes do not occur in pre-pubertal girls, Turner’s Syndrome, >25% of menopausal women, older postmenopausal women
List some DDx for hot flushes
- Fever
- Anxiety
- Alcohol consumption
- Narcotic withdrawal
- Migraine
- Parkinson’s disease
Hormonal
- Diabetes
- Hyperthyroidism
- Pheochromocytoma
Autoimmune/allergy
- Anaphylaxis
- Rosacea
Others
- Carcinoid
- ‘Dumping’ syndrome
- Renal cell carcinoma
- Cushing Syndrome
- Thyroid carcinoma
- Alcohol dehydrogenase deficiency
- Medication side-effects
Describe some psychological symptoms and long term consequences of menopause
Psychological Symptoms
- Low Mood: Depression
- Short-term memory lapse- ‘Brain fog’: very common experience but not really detectable on cognitive function tests
- Lack of energy
- Secondary to body changes
- Body image
- Low self-confidence
- Anxiety, panic attacks ⇔ hot flushes
Long Term Consequences of Menopause
- Bone loss
- Increased bone reabsorption
- Cardiovascular risk increase
- Central abdominal weight gain
- Conversion to a more adverse lipid profile
- Urogenital
- Stress and urge incontinence
- Dyspareunia
Describe post-menopausal fractures
Osteoporosis: “A systemic disease characterized by low bone mass and micro- architectural deterioration of bone tissue, leading to enhanced bone fragility and a consequent increase in fracture risk”
- 1 in 3 women aged >50y will suffer an osteoporotic fracture
- Initially wrist and vertebral fractures, femur and vertebral fractures rise.
- Associated with
- Increased mortality
- Increased morbidity
- Increased disability and reduced quality of life
List cardiovascular risk factors
- Obesity
- Body fat distribution
- Lipids and lipoproteins
- Glucose and insulin metabolism
- Arterial function (stiffer arteries)
- Blood pressure
- Coagulation and fibrinolysis
- Homocysteine
- Inflammatory markers
- Lifestyle – Smoking
