Menopause Flashcards
___ is the permanent cessation of menstruation, caused by failure of ovarian follicular development in the presence of adequate gonadotropin stimulation
Menopause
____ is the physiologic period in a women’s life during which there is regression of ovarian function
Climacteric
_____ is cessation of menstruation due to depletion of ovarian follicles < 40 y/o
Premature Ovarian Failure
What is the average age for menopause to occur?
Median –> 51.4 y/o
range of 48-55 yrs
What is the average age for the start of Climacteric to occur
47.5 years
What is the average length of time for the transition from Climacteric–> menopause to occur
Median length of 4 years
____ is caused by genetic abnormalities on the long and short arm of X chromosome
Premature menopause
~___% of women who go through early menopause is due to surgery
30%
What is associated w/ earlier menopause?
FHx of early menopause Smoking Blindness Abnormal chromosome karyotype Precocious puberty Left-handedness
What contributes to a later onset of menopause?
Obesity
Higher socioeconomic class
What are the 2 types of menopause?
Physiologic
Iatrogenic (surgery, radiation, chemotherapy)
Autoimmune ovarian tissue destruction
Infection/tumor ovary killers
Most follicular loss is due to ____, not ovulation
atresia
Ovarian atresia accelerates at around age ___
37 y/o
T/F: Loss of viable ovaries is the prime causative agent for the decrease in fertility for women
F: Age-related UTERINE changes also contribute to decreased fertility
Fill in the Blank!
During perimenopause…
The ovaries begin decreasing in __1__.
__2__ is still the dominant estrogen but the amount secreted decreases.
Number of follicles __3__ substantially.
Production of __4__ decreases.
Remaining follicles respond poorly to elevated __5a_ and _5b__
Erratic ovulation results in menstrual cycle __6__
- size
- Estradiol
- decreases
- inhibin
5a. FSH 5b. LH - irregularity
Do perimenopausal women need contraception?
YES!
*natural pregnancy is possible until menopause if reached
___is produced in the gonads, pituitary gland, placenta, corpus luteum and other organs.
Inhibin
What stimulates the secretion ofinhibinfrom the granulosa cells of the ovarian follicles in the ovaries?
FSH
What suppresses the production of FSH?
Inhibin!
yep, they control each other…
As follicles age, they become less capable of making ____
Inhibin
** this is a sign that follicles are more difficult to stimulate
What is the job of inhibin?
It inhibits (haha) secretion of FSH and LH
What will happen in each cycle if inhibin gets lower and lower?
FSH and LH remain high
What are elevations of FSH predictive of, particularly at the beginning of a cycle? What does it therefore impact?
Perimenopause
Fertility of remaining ova
When does fertility begin to wane?
35-37 y/o
By age 45, risk of spontaneous miscarriage increases to __%
50%
When during the cycle do you perform the FSH test?
Day 3 of cyle
What does it mean if the FSH is elevated on day 3 of the cycle?
Ovarian reserve is reduced
- few eggs remain
- egg quality is also reduced
**FSH increases w/ age!
Normal Day 3 FSH < __
Diminished reserve when FSH >__
<9
<11
- *Normal FSH does NOT guarantee good egg quality and ovarian reserve
- *Abnormal day 3 FSH is highly predictive of poor reserve/quality
Perimenopause is characterized by the shortening of _____, and/or the presence of _____ cycles.
Shortening of the ____ phase with a lower number of follicles recruited per cycle
Menstrual cycle length
anovulatory/ prolonged
follicular
Subtle hormonal changes occur during the ___ (decade)
Sx noticeable during the ___ (decade)
30s
40s
Most women menstruate ~___ (#) times between menarche and menopause
400 #Gross #ThatsALotOfTampons
With menopause, the ovary is no longer capable of responding to pituitary gonadotropins → so there is a ↓ production of ___ and ___
estrogen and progesterone
What happens to the following serum hormone levels at menopause (↑/↓/=)
___Circulating estrogens
___Ratio of estrogen to androgen
___Sex hormone-binding globulin secretion
___Peripheral aromatization of DHEA to estrone
___E2:E1 ratio
___Circulating bioavailable testosterone
↓ Circulating estrogens
↓ Ratio of estrogen to androgen
↓ Sex hormone-binding globulin secretion
↑ Peripheral aromatization of DHEA to estrone
↓ E2:E1 ratio
= Circulating bioavailable testosterone
What cells make estrogen?
Granulosa
Theca
Explain the pathophysiology in a stepwise manner to describe the decrease of estrogen and increase of FSH + LH
- Degeneration of granulosa and theca cells
- Failure to respond to endogenous gonadotropins
- ↓ Estrogen
- ↑ FSH and LH
T/F: Estrogen levels are a good indication of ovulation, fertility and the start of menopause?
F!
Estrogen levels fluctuate wildly
It is impossible to predict ovulation, the date of the cycle, fertility, or how soon menopause will arrive based on estrogen levels
What test is used to determine the start of perimenopause/menopause?
FSH
What are normal lab values for serum estrogen during the mid-follicular/periovulatory/mid-luteal phase?
What are normal estrogen values for post menopausal women?
30-450 ish (see all the details in the study guide)
0-40
What endocrine things contribute to the androgen effects of menopause?
testosterone (overall levels are decreased but less is converted to estrogen)
5-DTH - more circulating due to changes in binding proteins in the blood stream
____ is the placental estrogen and it is only seen in large amounts during pregnancy. High levels of ______ reflect fetal well being. It is the least potent of all estrogens. It originates from the fetal adrenal gland in the form of DHEA Sulfate and then is finally transformed to _____ in the placenta by the sulfatase enzyme. (Same answer in all blanks)
Estriol
___ is the predominant estrogen of women after puberty and prior to menopause. It has the highest effect on receptors
Where is this made?
Estradiol
Ovaries
___ is the predominant estrogen present in menopause. It is produced by aromatization of androstenedione in peripheral (fatty) tissue. It is less potent than Estradiol.
Where is this made?
Estrone
peripheral conversion of androstenedione
What are the target organs of estrogen? (x5)
CV System Urogenital system Bone and teeth Skin Brain
What sx are related to ↓ estrogen (x6)
Vasomotor instability Altered menstrual function Vaginal atrophy Skin thinning Urinary tract sx Osteoporosis
____ are characterized by a rise in skin temperature, dilation of peripheral blood vessels, increased blood flow in the hands, increased skin conductance, and transient increase in heart rate followed by a temperature drop and profuse perspiration over the area of flush distribution.
Vasomotor flushes/flashes
What other sx may accompany a hot flash?
Night sweats Dizziness Nausea HA Palpitations
Where/What is the “thermostat” of the body?
Hypothalamus
***thermo neutral zone becomes narrow w/ menopause, which has to do w/ feedback at the NE receptor of the hypothalamus, which is affected by decreased estrogen.
What are probable causes of hot flashes?
Ovary - estrogen thing
Pituitary - LH decrease
Hypothalamic - norepinephrine
The ____ theory says that hot flashes are caused by the removal of sex hormones after the body has been exposed to them for a period of time–> IOW, “dynamic” loss of sex hormones
Gonadal
What are arguments for the gonadal theory
- low E
- orchiectomy = hot flashes in men
- hot flashes go away if hormone is replaced
The ___ theory states that extreme rise(s) in FSH/ LH are the cause of hot flashes
Pituitary theory
What are arguments for the pituitary theory
Against?
FOR
- high LH related to hot flash
AGAINST
- Turners and Kallman pts alwasy ahve high FSH and LH but they dont haev hot flashes
The ___ theory states that inhibition of hypothalamic catecholamines (such as _____) are the cause of hot flashes
Hypothalamic
norepinephrine
The onset of hot-flashes occurs in…
__% prior to menopause (up to 1 year or more)
__% after cessation of menses
10%
50%
Hot flashes usually have an ___ onset and last anywhere from __ sec – __ min
abrupt
30 sec- 5-10 min
___ is the leading cause of death in the US – twice as many women die of from this rather than of CA
CV disease
By 6-10 years after menopause, incidence rates of coronary heart disease are in (higher/lower/equal) women and men
about equal
____ increases significantly at 1-2 yrs or more after the menopause, and becomes less cardioprotective
Serum cholesterol
What genital changes occur during menopause?
Atrophy Descent of the uterus 30% drop in urethral closure pressure Atrophic urethritis Atrophic cystitis
Genital changes can lead to what sx?
Atrophy–> itching, burning, dysparunia
Descent of the uterus –> prolapse
drop in urethral closure –> incontinence
Atrophic urethritis/cystitis –> urgency, frequency, dysuria
What are the 3 most common fx in postmenopausal women?
vertebrae
distal radius
neck of femur
__% of women have radiological evidence of osteoporosis by 60
After age 65 ___ have a vertebral fx
By age 80, ___ have fractured a hip
25%
1/3
1/4
____% of women with hip fx after 80 y/o will die of complications within 6 months
15% of women w/ hip fx after 80 y/o will die of complications w/in 6 months
Initial period of up to 4-5 years after menopause, there is accelerated loss of bone at rate of ___% per year– mainly ____ bone at first, and later, ____ bone as well.
1-2%
trabecular
cortical
What are RF for osteoporosis? (FYI)
White/Asian low BMI early menopause FHx low Ca++ diet high caffeine/alcohol/protein/smoking endocrine stuff
What are neurologic sx of menopause?
Anxiety/depression irritability fatigue HA tiredness/lethargy nervousness sleep difficulties inability to concentrate
Postmenopausal women have lower level of plasma ____ which may contribute to the neurologic sx of menopause
β-endorphin
What is the tx for menopausal sx?
low doses of estrogen +/- progesterone (depending on whether your patient has a uterus or not).
What is the #1 rule in HRT for women in menopause?
DO not give unopposed estrogen to a woman with a uterus
**Give the lowest dose that will effectively tx sxs
Females have a __ chance of developing breast CA in their life
1/8
What factor is responsible for the highest increased risk of developing breast CA?
FHx of breast CA
Compared w/ the placebo, estrogen + progestin resulted in an increase in? (x4)
Decrease in? (x2)
Increased risk
- heart attack
- stroke
- blood clots
- breast cancer
Reduced risk
- colorectal CA
- Fx
**No protection against mild cognitive impairment and increased risk of dementia
Compared w/ the placebo, estrogen alone resulted in:
Increased risk
- stroke
- blood clots
Reduced risk of fx
Uncertain effect for breast CA
No difference in risk
- heart attack
- colorectal cancer
What are the benefits of using vaginal estrogen therapy?
What doesn’t it help?
Helps
- local sxs
- doesn’t absorb as well (less systemic effects)
- Helps both vaginal and urethral sxs
Won’t help hot flashes
What are some side effects of vaginal estrogen?
abnormal vaginal bleeding
breast pain
N
