Metabolic and Menopause Flashcards
What stimulates releaase of FSH and LH from the pituitary?
GnRH from hypothalamus
effect of FSH/LH on uterus and ovary
release estrogen and progesterone
Progesterone has ____ effect on GnRH release
negative
is a syndrome of ovarian dysfunction affecting 6-8% of reproductive age women worldwide. The most common endocrine abnormality of women of reproductive age.
• Its clinical manifestations include: chronic anovulation (oligo/amenorrhea, infertility) and hyperandrogenism (hirsutism, acne, alopecia).
PCOS
Define PCOS
what risks are associated with it?
The syndrome is defined by a clustering of signs and features, where no single test is diagnostic.
• PCOS is associated with an increased risk of diabetes and other metabolic abnormalities which may potentially increase the risk of coronary artery disease
Clinical Manifestations of PCOS Hyperandrogenism
Hirsutism, acne, alopecia, deepening voice, more muscle, clitoromegaly often peripubetal onset
Pathophysciology of PCOS?
Complex disorder and partially understood
Gonadotropin secretion disturbance
Steroidogenesis disorder
Insulin resistance
Explain pathphys of PCOS in relationship to high androgens effect on:
skin:
insulin:
adipose tissue:
Skin: hirsutism, acne, acnothosis nigrans
INuslin: insuiln resistance
Adipose: increase estrone production causing endometiral hyperplasia as well as follicular atresian = anovulation/amneorrhea
We get tons of androgen production in PCOS becse the ____ is stimulated by a high LH:FSH ratio from abnormal androgen and estrone feedback
ovary or theca
LH stimulstes the ____ cell to make testosterone and androstendione from cholesterol
Theca cell
FSH stimulates the ___ cell to make estradiol and DHT from androstendione and testosterone it gets from the Thecal cell
Granulosa cell
High levels of ___ and ___ INCREASE thecal cell production of more androstendion and testesterone
IFG and INhibin
also insulin increases prodcution!!!
we see ____ in lean and obese women with PCOS compared to otehr women
insulin resistance (thus encourages Thecal cell to make androgens)
Dx criteria for PCOS
at least 2 of the 3:
- Oligo- or anovulation
- Clinical and/or biochemical signs of hyperandrogenism
• Polycystic ovaries on imaging
And
• Absence of secondary causes (CAH, androgen-secreting tumors, Cushing’s syndrome)
Similarities of PCOS and Metabolic Syndrome Related to Insulin Resistance
- Central obesity
- Hyperinsulinemia
- Low SHBG
- Abnormal lipids (elevated TG, low HDL)
- Higher prevalence of IGT and diabetes.
- Increased risk of non alcoholic steatohepatitis (fatty liver).
Dx of PCOS
- Diagnosis of PCOS made based on history, clinical suspicion
- Biochemical evaluation is for excluding less common causes of hirsutism and menstrual irregularities (androgen secreting tumors, CAH, thyroid disease)
- Biochemical testing will often result in “normal” results
- Tests for insulin resistance are not required to make a diagnosis of PCOS
Mangement of PCOS; tx complaint and think about long term issues:
• Treatment of symptoms of anovulation :
- regulate menses
- induce ovulation
- endometrial cancer risk reduction
• Treatment of obesity and metabolic disorders in women with PCOS includes:
- Obesity management
- Sleep apnea screening
- Diabetes prevention
-Lipid management and cardiovascular disease risk reduction
Treat symptoms of hyperandrogenism and screen for anxiety and depresssion
in women with PCOS
HOw do OCPS help tx PCOS?
Suppress ovarian androgen secretion by suppression of gonadotropins
Increases SHBG
Decreases free testosterone and free androgen index
Improves hirsutism
Regulates menses and provides adequate progestin to protect endometrial lining (lowers risk for endometrial hyperplasia)
• Competitive inhibitor of androgen receptor
- Improves hirsutism, acne and alopecia
- Does not inhibit androgen secretion
- Requires reliable contraception
used to tx PCOS
spironolactone
the final menstrual period and is usually confirmed when a woman has missed her period for 12 consecutive months (in the absence of other obvious causes).
• It reflects complete or near complete depletion of ovarian follicles and absence of ovarian estrogen secretion. It marks the permanent end of fertility.
• Menopause
Age of menopause and what is it influenced by?
- Average age is 51, but age ranges from 40 to early 60s. (occurs after 55 in 5% and between 40-45 in 5%.
- Age of menopause influenced by genetics, ethnicity, smoking, and reproductive history.
It can last 6 years or more and ends 1 year after the final menstrual
period.
Perimenopause/Menopause Transition
Interval of amenorrhea >60 days with elevated FSH during cycle, and start to see VMS
late transition to menopause
Pt has amenorrhea, highly variable FSH with VMS
EArly post menopause
pt has amnenhorrea, stable FHS, increaseing UG atrophy
Late post menopause
Vasomotor symptoms, sleep disturbance and depression are ___ signs of meonopause
GOOD evidence
FAir evidence of menopause
cognitive dysnfx, urinary incontinence,sexual dysfunx
Consequences of Estrogen Deficiency in the Postmenopausal Years
- Increased risk of osteoporosis
- Increased risk of diabetes
- Increased risk of CHD and CVD
- Changes in body composition-_increased fat mass_
• Skin changes
early tests where they gave women E+P for postmenopause discontinued bc?
What about Estrogen only?
average follow up 5.2 years due to increased breast cancer, CHD, stroke, VTE
Estrogen only: increased risk of stroke
Observational studies had different results then the WHI:
VMS
Age at HT initiaion
time since menopause
BMI:
Yes had VMS
initiated at 52 yrs
2 yrs since menopause
BMI 24-25
- relieves VMS and relieves vaginal atrophy
- blocks bone resorption (approved for prevention of osteoporosis)
• provides endometrial protection and an alternative to progestogen therapy for women with a uterus who are averse to vaginal bleeding, breast tenderness, or altered mood.
The combination of CEE with the SERM bazedoxifene (BZA)
provides endometrial protection and an alternative to progestogen therapy for women with a uterus who are averse to vaginal bleeding, breast tenderness, or altered mood.
Bazedoxifene
Current Indications for
Menopausal Hormone Therapy (MHT)
Younger symptomatic postmenopausal women less than a decade from final menstrual period and without increased risk for CHD and breast cancer with LOWEST possible dose
must be prescribed with systemic ET for uterine protection in women who have a uterus
Progestin or the SERM bazedoxifene
MHT is not indicated for
prevention of chronic disease (CHD, breast cancer, dementia, etc)
For isolated vaginal symptoms, both systemic and vaginal estrogens are effective
VAGINAL ESTROGEN
V is preferred for isolated vaginal symptoms– vaginal dryness, dyspareunia—given its potent local effect and minimal degree of systemic absorption.
vaginal estrogen
***dont need progestin even if they have uterus if given at LOW does
SERM taken orally for atrophic vaginitis and dyspareunia
OSPEMIFENE
NOn hormone alternatives for vasomotor symptoms
SSRI/SNRI- paroxetine, venlafaxine, etc Gabapentin
Clonidine
• has important systemic effects affecting the risk of cardiovascular disease, osteoporosis, and endometrial and breast cancer
Estrogen
• is the most effective treatment for vasomotor symptoms
Estrogen
is safe for the majority of symptomatic, younger, healthy postmenopausal women for short term use for treatment of vasomotor symptoms and osteoporosis prevention and treatment
Estrogen therapy
Unopposed estrogen is contraindicated in women
with a uterus
