Menopause + HRT + Post Menopausal Osteoporosis
Definitions:
- Menopause:
o Permanent cessation of menstruation due to loss of ovarian follicular
activity. Confirmed after 12 months of cessation with no other cause.
o The state associated with physical symptoms and with metabolic and
structural changes related to declining estrogen levels
o Typically, at age 50
o Women now live approximately 33% of their lives in post menopause.
- Menopausal transition:
o is the progressive endocrinologic continuum from regular, predictable
menses to ovarian senescence and menopause
o typically begins mid-40. Lasts 4-7 years
- Premature ovarian failure:
o Persistent elevation of FSH and cessation of menses before age 40.
o Increased FSH on 2 samples taken 4-6 weeks apart.
- Factors influencing onset of menopause:
o Decrease age of onset: smoking, ovarian surgery, and pelvic radiation
all advance menopause.
o Increase Age: No major modifiable factor is known to delay
menopause
- Cut off point of serum oestrogen for diagnosis of ovarian failure is 20 pg/ml
FSH > 40 IU/L 2 samples 4-6 weeks apart.
- Average number of ovulatory cycle in a female reproductive life = 400
Age, transition, risk factors and symptoms
- Mean menopause age = 51 years in US women
- Factors that decrease age of menopause:
o Smoking, low BMI, race , can shift this range, but only by a few years.
o Menopause occurring before 45 years (is considered early
menopause) and is mainly due to X- chromosomal abnormality –
, turners’ syndrome, X chromosome changes.
o This is different from premature ovarian failure which occurs before 40
years.
- Increase Age: No major modifiable factor is known to delay menopause
Hormonal axis and endocrine changes
- GnRH is released from the arcuate nucleus of the medial basal
hypothalamus in a pulsatile fashion, stimulating FSH and LH from the
pituitary
- Ovarian function declines ↓ ovarian steroids ↑amplitude and frequency
of GnRH ↑FSH and LH.
- Loss on inhibin also contributes to increase FSH
- FSH rises more than LH (due to loss of inhibin B)
- In postmenopausal women estorgen can come from 3 sources:
o Exogenous replacement
o Extragonadal conversion (adipose tissue)
o Effects of decreased sex hormone binding globulin.
SHBG bind to oestrogen in the blood, when there is less SHBG,
any oestrogen present is more bioavailable, unopposed and can
exert its effect on cells.
Menopausal transition:
o Clinically: women in late reproductive years may have regular cycles,
but with symptoms of hot flushes
This is due to declining oestrogen high FSH.
Normal progesterone levels.
o Therefore, symptoms are due to a drop in oestrogen levels, and low-
dose estrogen supplementation can be started to alleviate symptom,
typical regimens are:
, 0.3 mg conjugated equine estrogen
O.3 mg estrone sulphate
0.5 mg micronized estradiol.
From day 5 after menstruation until the next cycle.
o Since progesterone is normal, and this is not yet true menopause,
oestrgen alone supplementation can be used without increased risk.
o Ovulation can sill occur if progesterone is normal contraception is
required until menopause is confirmed.
Histology and sonographic findings:
- Normal histology in aging ovary reveals multiple Corpora albicans
o These are old/ regressed CLs.
o CL is yellow, albicans are pale white and fibrous looking.
Corpora albicans
- Ovarian histology post menopause:
o Follicles are depleted
o Granulosa/ theca cells degenerate
o Stroma and surface epithelial cells unchanged/ persist.
- Changes in cytology – predominance of parabasal cells.
o Usually, parabasal cells are found in deeper layer of the vagina lining
but due to drop in oestrogen levels, the normal mature squamous cells
Definitions:
- Menopause:
o Permanent cessation of menstruation due to loss of ovarian follicular
activity. Confirmed after 12 months of cessation with no other cause.
o The state associated with physical symptoms and with metabolic and
structural changes related to declining estrogen levels
o Typically, at age 50
o Women now live approximately 33% of their lives in post menopause.
- Menopausal transition:
o is the progressive endocrinologic continuum from regular, predictable
menses to ovarian senescence and menopause
o typically begins mid-40. Lasts 4-7 years
- Premature ovarian failure:
o Persistent elevation of FSH and cessation of menses before age 40.
o Increased FSH on 2 samples taken 4-6 weeks apart.
- Factors influencing onset of menopause:
o Decrease age of onset: smoking, ovarian surgery, and pelvic radiation
all advance menopause.
o Increase Age: No major modifiable factor is known to delay
menopause
- Cut off point of serum oestrogen for diagnosis of ovarian failure is 20 pg/ml
FSH > 40 IU/L 2 samples 4-6 weeks apart.
- Average number of ovulatory cycle in a female reproductive life = 400
Age, transition, risk factors and symptoms
- Mean menopause age = 51 years in US women
- Factors that decrease age of menopause:
o Smoking, low BMI, race , can shift this range, but only by a few years.
o Menopause occurring before 45 years (is considered early
menopause) and is mainly due to X- chromosomal abnormality –
, turners’ syndrome, X chromosome changes.
o This is different from premature ovarian failure which occurs before 40
years.
- Increase Age: No major modifiable factor is known to delay menopause
Hormonal axis and endocrine changes
- GnRH is released from the arcuate nucleus of the medial basal
hypothalamus in a pulsatile fashion, stimulating FSH and LH from the
pituitary
- Ovarian function declines ↓ ovarian steroids ↑amplitude and frequency
of GnRH ↑FSH and LH.
- Loss on inhibin also contributes to increase FSH
- FSH rises more than LH (due to loss of inhibin B)
- In postmenopausal women estorgen can come from 3 sources:
o Exogenous replacement
o Extragonadal conversion (adipose tissue)
o Effects of decreased sex hormone binding globulin.
SHBG bind to oestrogen in the blood, when there is less SHBG,
any oestrogen present is more bioavailable, unopposed and can
exert its effect on cells.
Menopausal transition:
o Clinically: women in late reproductive years may have regular cycles,
but with symptoms of hot flushes
This is due to declining oestrogen high FSH.
Normal progesterone levels.
o Therefore, symptoms are due to a drop in oestrogen levels, and low-
dose estrogen supplementation can be started to alleviate symptom,
typical regimens are:
, 0.3 mg conjugated equine estrogen
O.3 mg estrone sulphate
0.5 mg micronized estradiol.
From day 5 after menstruation until the next cycle.
o Since progesterone is normal, and this is not yet true menopause,
oestrgen alone supplementation can be used without increased risk.
o Ovulation can sill occur if progesterone is normal contraception is
required until menopause is confirmed.
Histology and sonographic findings:
- Normal histology in aging ovary reveals multiple Corpora albicans
o These are old/ regressed CLs.
o CL is yellow, albicans are pale white and fibrous looking.
Corpora albicans
- Ovarian histology post menopause:
o Follicles are depleted
o Granulosa/ theca cells degenerate
o Stroma and surface epithelial cells unchanged/ persist.
- Changes in cytology – predominance of parabasal cells.
o Usually, parabasal cells are found in deeper layer of the vagina lining
but due to drop in oestrogen levels, the normal mature squamous cells
