LM 17.1: Menopause

Question 1

what is STRAW?

Answer 1

states of reproductive aging workshop

this classification incorporates what the female experiences as it relates to symptoms of changes in the mesntrual cycle, vasomotor symptoms and urogenital atrophy as well as the endocrinology changes

previously this system was not recommended for smokers, BMI > 30, heavy aerobic activity, chronic menstrual irregularity, uterine/ovarian abnormalities or significant illness like cancer

Question 2

what is the definition of menopause?

Answer 2

no menses for 12 months in the absence of hormonal treatment

indicates the depletion of ovarian follicles

it’s diagnosis based on historical information

Question 3

what happens in perimenopausal?

Answer 3

reduced ability of aging follicles to secrete inhibin from granulosa cells of the follicles

decreased inhibin decreases negative feedback to anterior pituitary so there’s increased FSH and estrogen levels rise

Question 4

what happens during menopause?

Answer 4

once all the follicles die, there’s decreased estrogen too which results in really high levels of GnRH, LH, and FSH

Question 5

what causes hot flashes? how does estrogen play a role?

Answer 5

disfunction of the thermoregulatory nucleus of the hypothalamus which regulates sweating and vasodilation normally

it is thought that women with hot flashes have a narrow thermoregulatory zone because the withdrawal or rapid fluctuations in estrogen levels lead toa decrease in norepinephrine and serotonin which lowers the thermoregulatory set point –> this which means that minimal changes in temperature can cause a hot flash that results in sweating to try and cool off the body because the thermoregulatory zone has been narrowed causing a lower threshold to trigger the physiologic response of “I’m too hot”

also it is hypothesized that a drop in estrogen increases neurotransmitter concentrations in the hypothalamus which creates a narrower thermoregulatory zone; NE and serotonin may also decrease the thermoregulatory set point

Question 6

why does osteoporosis happen during menopause?

Answer 6

in normal bone remodeling there’s osteoclasts and osteoblasts that breakdown and build bones

osteoblasts make RANK-L and OPG –> RANK-L binds to RANK on the osteoclast progenitor cells which promotes osteoclast formation and bone resorption –> OPG binds to RANK-L which prevents it from binding to RANK and activating osteoclasts

in menopause there’s lower estrogen and RANK-L production outnumbers OPG so bone resorption is favored without OPG there to inhibit osteoclast formation

Question 7

what is the best treatment for hot flashes?

Answer 7

menopausal hormone therapy can help with hot flashes and bone fractures!

however you want to use the minimal dose and for the shortest amount of time

Question 8

why do women taking hormone therapy with a uterus need progestin too?

Answer 8

for women with an intact uterus, progestin therapy must be added to prevent endometrial hyperplasia and cancer

Question 9

what are the risks associated with combined estrogen/progesterone hormone therapy?

Answer 9

1. breast cancer
2. stroke
3. CVD
4. venous thromboembolism

Question 10

what are the risks associated with estrogen hormone therapy?

Answer 10

1. stroke
2. venous thromboembolism

this is only given to women without a uterus

Question 11

what is the alternate treatment for hot flashes other than hormone replacement?

Answer 11

1. gabapentine
2. clonidine
3. SSRIs/SNRIs

Question 12

how does clonidine help with hot flashes?

Answer 12

clonidine is an alpha2 adrenergic agonist so it inhibits release of NE

without NE, the thermodynamic set point results to normal

Question 13

how many oocytes does a woman have?

Answer 13

6-7 million at 20 weeks in utero

1 million at birth

400,000 at puberty

200-300 at menopause

Question 14

what are the symptoms of perimenopause?

Answer 14

1. shortening or lengthening of cycles
2. variable follicular phase
3. hot flashes

Question 15

how is the uritogenital system effected during menopause?

Answer 15

vaginal atrophy and dryness

pelvic organ prolapse and atrophic urethritis can happen too when the tissues supporting them atrophy which can lead to dyspareunia and incontinence

lack of estrogen can lead to:
1. urethritis with dysuria not due to UTI

2. increased risk of UTI due to decreased vaginal pH
3. increased incidence of urethral caruncle
4. incontinence
5. frequency
6. not a cause of pelvic prolapse

Question 16

how do you know if irregular uterine bleeding is due to menopause?

Answer 16

irregular bleeding due to the menopause transition is a diagnosis of exclusion

Question 17

what hormones do granulosa cells produce? what do they do?

Answer 17

estrogen and inhibin

inhibin B is negative feedback to FSH

estrogen also provides negative feedback but inhibin is the bigger contributor as estrogen replacement in postmenopausal women does not change the FSH

Question 18

what happens to the dominant follicle with age?

Answer 18

with increased age, the FSH rescue of the dominant follicle from atresia occurs with less frequency and requires higher levels of FSH as the ovarian reserve declines

decline in ovarian follicles results in decline in estrogen and inhibin production which first leads to shorter menstrual cycles due to a shorter follicular phase

sometimes there’s skipped menses when no dominant follicle is rescued and ovulation doesn’t even occur

Question 19

what is the genitourinary syndrome of menopause?

Answer 19

vulvar and vaginal tissues are estrogen sensitive so with the absence of estrogen:

1. vagina decreases in collage and adipose as well as water retention, vaginal walls shrink and rug flatter or disappear, decreased ratio of superficial squamous cells:basal cells, decrease in pH with loss of lactobacilli, dyspareunia due to loss of elasticity and moisture
2. vulva decreased activity of sebaceous glands, decreased adipose deposition, decrease in size of labor

Question 20

how is cardiac health effected by menopause?

Answer 20

the decrease in estrogen negatively effects the lipid profile leading to increase in LDL and subsequent increase in CVD