Ex3 L12 - Menopause, Osteoporosis, and Andropause Flashcards
What is menopause?
The point in time when menstruation ceases as a result of an age-related depletion of ovarian oocytes.
What is perimenopause?
begins with the first skipped or irregular period
What is the median age of perimenopause onset?
47 years.
What is the median age of the FMP?
final menstrual period: 51.4 years.
Describe the menstrual cycle
Day 0: menses
Days 4-14: follicular phase for the ovary and proliferative phase for the uterus
Day 14: ovulation
Days 14-28: luteal phase for the ovary and secretory phase for the uterus
Describe the two-cell theory of estrogen production
- FSH acts on granulosa cells to stimulate follicle growth and estrogen production.
- LH acts on theca cells to stimulate androgen production; LH surge triggers ovulation.
Granulosa cells express…
aromatase
What does HPG axis stand for?
hypothalamus, pituitary, gonadal axis
What effect does estrogen production have on the HPG axis?
negative feedback, until is reaches a certain level and then the feedback flips to positive and causes the LH surge
How does the number of ovarian germ cells/follicles change over time?
- there is a finite amount, and they do not regenerate after birth
- almost 50% is lost before birth
- depletion occurs because of ovulation and atresia
- follicle numbers reach a critical threshold around age 40, where atresia increases rapidly and there is irregular cycling and hormonal fluctuations. This is the menopausal transition known as perimenopause
What happens to the HPG axis with menopause?
Diminished follicle pool reduces ovarian production of estradiol and inhibin, leading to increased FSH levels and ovulatory failure.
It also becomes insensitive to estradiol positive feedback, which contributes to ovulatory failure and hot flashes.
How do the ovaries change with age?
- overall reduced ovarian size (follicles are the bulk of the volume)
- diminished ovarian vascularity
- more small, pre-ovulatory follicles and fewer granulosa cells
What are some factors that can affect the age of menopause onset?
Genetics, age of first menstrual period, gestational age, BMI, and unilateral oophorectomy.
What is primary ovarian insufficiency?
Depletion or dysfunction of ovarian follicles and cessation of menses prior to age 40, also known as premature ovarian failure.
What are the causes, manifestations, and mechanisms of primary ovarian insufficiency?
causes: genetic or chemo/radiation
manifests as menopause but is not age-related
mechanisms: reduced follicle number (started low or degenerated quickly) or dysfunctional follicle pool (lack of estrogen or unresponsive to LH/FSH)
How does menopause lead to osteoporosis?
- estrogen activates osteoblasts and inhibits osteoclasts
- low estrogen leads to more bone resorption than formation
- pushes bone closer to the fracture threshold
What are some prevention strategies for osteoporosis?
Exercise (strength training, need load for increased bone formation), adequate calcium intake, maintain vitamin D levels, avoid heavy drinking, and don’t smoke.
What are bisphosphonates used for?
Treat osteoporosis by binding to hydroxyapatite in bone, inhibiting osteoclast proliferation, and inducing osteoclast apoptosis.
What are the side effects of bisphosphonates?
- musculoskeletal pain
- heartburn and ulcers
- osteonecrosis of the jaw
- side effects worsen with long term use
What is hormone replacement therapy/estrogen replacement therapy?
- replacement of estrogen lost at menopause, for side effects of menopause (approved 1942) or osteoporosis (approved 1988)
What controversies on HRT were pointed out by the Women’s Health Initiative?
- before 1975 estrogen was used, increased the risk for endometrial cancer, but combining with progestin reduced that risk
- controversial data on coronary heart disease risk
- WHI concluded that there is age stratification, with protective effects in women <60
What are the benefits of hormone replacement therapy (HRT)?
Prevention of osteoporosis, alleviation of menopausal symptoms, cardioprotection if started before age 60, and overall reduced mortality rate
What are the risks associated with hormone replacement therapy?
Potential coronary heart disease risk if started after age 60, and an increased risk of breast cancer depending on type of progesterone and SERMs
What are SERMs?
selective estrogen receptor modulators
Describe the male two cell model/HPG axis?
FSH stimulates sertoli cells, which produce inhibin to inhibit the anterior pituitary production of FSH
LH stimulates Leydig cells, which produce testosterone and have negative feedback on the hypothalamus and anterior pituitary
What happens to testosterone with age?
free testosterone declines…more travels in the blood bound to sex hormone binding globulin (SHBG) which does not have the same effects as free T
What is male hypogonadism?
A condition characterized by low serum testosterone levels (below 200 ng/mL) and symptoms like fatigue, low libido, and reduced muscle mass (which can start at 200-400 ng/mL)
What are the symptoms of male hypogonadism?
- fatigue and loss of energy
- low libido and erectile dysfunction
- reduced muscle mass
- increased fat mass
- osteoporosis
What are the benefits of testosterone replacement therapy (TRT)?
Improves muscle mass and bone density, restores libido and erectile function, and alleviates other symptoms of hypogonadism.
What are the risks of testosterone replacement therapy (TRT)?
- prostate cancer (depending on SARMs)
- cardiovascular disease or cardiovascular events
Why is the term ‘andropause’ considered inaccurate?
Androgen production does not cease entirely but declines with age, and symptoms may be over-diagnosed or over-treated as hypogonadism when they really are due to other problems
