✓ 31- Menopause and Premature Ovarian Failure Flashcards
What is the average of menopause in Kuwait?
51
What is the landmark for menopause?
Final menstrual period
Define Perimenopause
Menopause transition + 1 year after FMP
Define Early and Late Postmenopause
Early: 5-8 years following FMP
Late: rest of life
What are the stages of menopausal transition?
Early and Late menopausal transition
Define Early and Late Menopausal transition
Early: variable duration
Late: 1-3 before FMP
What is the clinical definition of menopause?
menopause recognized after 12 years months of secondary amenorrhea
Epidemiology of Menopause [Age]
Average age = 51
5% after 55 and 5% between 40 and 45
What is the definition of POF/I?
Menopause before age of 40
What genetic factors affect early menopause?
Family history
Genes that regulate immune function and DNA repair Genetic variation in the estrogen receptor gene
FMR1 permutation (fragile X mental
retardation)
How does (fragile X mental retardation) affect menopause?
Associated with POF/I
Earlier menopause by up to 7 years
What factors affect early menopause?
Genetics Ethnicity Smoking Hysterectomy with ovarian consideration Other T1DM In-utero exposure to DES
How does smoking affect menopause?
Earlier menopause up to 2 years
Ethnicity and Menopause
Hispanic < Caucasian < Japanese-American women
How does a Hysterectomy with ovarian consideration cause menopause?
blood supply in the ovaries decreases, which accelerates the atresia that occurs in the follicles.
What are the three main steps in ovarian development?
Germ cell differentiation
Continuous follicular growth
Continuous follicular atresia
When does Germ cell differentiation occur?
At week 4-8 of development
Compare the antral follicles in adults and children/fetuses
Antral follicles is larger in children/fetuses, these are formed in response to low levels of pulsatile FSH and LH, unlike after puberty
What causes atresia?
apoptosis
What reduces the number of oocytes before birth?
Atresia
At which age does accelerated atresia occur?
> 37 years
How many oocytes are found at menopause?
1000 oocytes, but most atresic
At which age do females have the highest numbers of oocytes?
Female fetus at 20 weeks
How many oocytes are found at puberty?
200,000
What is the reproductive age?
15-45 years [first couple of cycles after puberty and last couple of cycle prior to menopause are anovulatory]
At which age do we see a rapid decline in number of follicles?
at 37
What is the first hormonal changes seen in early menopause and what does that correlate with?
Fall in Inhibit B, correlates with decrease in developing follicles
What hormonal changes are seen in early menopause?
↓ Inhibit B ↓ AMH ↑ FSH ↑LH ↑ Estrone ↓ Progesterone
What are the late symptoms of menopause?
Bone loss Cardiovascular disease (CVD) Degenerative arthritis Body composition Skin changes Balance Pelvic organ prolapse Urinary incontinence
What are the early symptoms of menopause?
Hot Flashes Sleep disturbances Depression Vaginal dryness & dyspareunia Painful intercourse Sexual dysfunction Cognitive impairment (memory & concentration) Joint pain Breast pain Migraines
What are three mechanisms in which estrogen deficiency may cause bone loss?
Increases bone remodeling rate
Increases osteoclasts and osteoblasts numbers [more osteoclasts]
Increases resorption and formation [more resorption]
How can estrogen effect bone?
↓ birth rate of osteoclasts
↑ osteoblasts progenitors in bone marrow
↑ pro-apoptotic effects on osteoclasts
↓ anti-apoptotic effects on mature osteoblasts & osteocytes
What is the t-score of osteopenia, osteoporosis and severe osteoporosis?
Osteopenia → between -1 and -2.5
Osteoporosis → -2.5 and below
Severe Osteoporosis → -2.5 and below + fragility fracture
What changes in lipid profiles is seen in post-menopausal women?
Small increase in LDL
No change in HDL, but decreased protective effects
Define POF/I
The development of primary hypogonadism
in females before the age of 40 years
Epidemiology of POF/I
1 in 250 by age 35 years
1 in 100 by age 40 years
What is the pathophysiology of POI/F?
Unknown etiology [>75%]
Accelerated follicle depletion
Abnormal follicular stimulation
What genetic defects cause accelerated follicular atresia?
Turner’s Syndrome
Fragile X Syndrome
X chromosome deletions and translocation
Galactosemia
What ovarian toxins cause accelerated follicular atresia?
Radiation
Mumps/CMV
Chemotherapeutic drugs [Alkylating agents]
What intraovarian modulators cause abnormal follicular stimulation?
BMP 15 [Polymorphism of Inhibit alpha subunit]
What steroidogenic enzyme defects cause abnormal follicular stimulation?
CYP17 deficiency [StAR mutation]
Aromatas gene mutations
What gonadotropin receptor function cause abnormal follicular stimulation?
FSH receptor mutations
Gs Alpha subunit gene mutations
Management of Autoimmune Oophoritis
HRT til 50 years [normal age of menopause]
Fertility
IVF with oocyte donation
Glucocorticoids
Investigations of Autoimmune Oophoritis
21-hydroxylase or anti-adrenals antibodies
Ovarian biopsy is unnecessary
What other condition has the same antibodies seen in autoimmune oophoritis?
Asymptomatic adrenal sufficiency
What antibodies are found in autoimmune oophoritis?
21-hydroxylase or anti-adrenals antibodies
Describe hot flashes
A sudden sensation of heat centered on the upper chest & face that rapidly becomes generalized, lasting 2-4 minutes.
What is the frequency of hot flashes attacks?
Occur 1/2 per day OR 1 per hour
Continues > 1 year [80%]
Resolves spontaneously within 4-5 years if left untreated
What do low serum AMH concentration indicates?
predictive of a poor ovarian response to exogenous
gonadotropin stimulation
marks a critical juncture in the timing of the menopausal transition
What hormonal changes indicate a decline in follicular numbers?
Inhibit B and AMH
What changes are seen in the Hypothalamic-Pituitary axis during the perimenopausal years?
Decreased sensitivity to estrogen
Failure of positive feedback of E on LH
normal preovulatory levels of estrogen, but no LH surge
Failure of negative feedback of E on LH
normal follicular phase estrogen levels do not suppress LH secretion
What is the cause of follicular atresia in fetus and adults?
Fetus:
apoptosis of oocyte
Adult:
Granulosa cell apoptosis
Describe follicular atresia in young girls
most follicles that reach the pre-antral (1 mm) stage are
already atretic, with the rate of atresia is increased in larger follicle
