Ex3 L12 - Menopause, Osteoporosis, and Andropause

Question 1

What is menopause?

Answer 1

The point in time when menstruation ceases as a result of an age-related depletion of ovarian oocytes.

Question 2

What is perimenopause?

Answer 2

begins with the first skipped or irregular period

Question 3

What is the median age of perimenopause onset?

Answer 3

47 years.

Question 4

What is the median age of the FMP?

Answer 4

final menstrual period: 51.4 years.

Question 5

Describe the menstrual cycle

Answer 5

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

Question 6

Describe the two-cell theory of estrogen production

Answer 6

• 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.

Question 7

Granulosa cells express…

Answer 7

aromatase

Question 8

What does HPG axis stand for?

Answer 8

hypothalamus, pituitary, gonadal axis

Question 9

What effect does estrogen production have on the HPG axis?

Answer 9

negative feedback, until is reaches a certain level and then the feedback flips to positive and causes the LH surge

Question 10

How does the number of ovarian germ cells/follicles change over time?

Answer 10

• 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

Question 11

What happens to the HPG axis with menopause?

Answer 11

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.

Question 12

How do the ovaries change with age?

Answer 12

• overall reduced ovarian size (follicles are the bulk of the volume)
• diminished ovarian vascularity
• more small, pre-ovulatory follicles and fewer granulosa cells

Question 13

What are some factors that can affect the age of menopause onset?

Answer 13

Genetics, age of first menstrual period, gestational age, BMI, and unilateral oophorectomy.

Question 14

What is primary ovarian insufficiency?

Answer 14

Depletion or dysfunction of ovarian follicles and cessation of menses prior to age 40, also known as premature ovarian failure.

Question 15

What are the causes, manifestations, and mechanisms of primary ovarian insufficiency?

Answer 15

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)

Question 16

How does menopause lead to osteoporosis?

Answer 16

• estrogen activates osteoblasts and inhibits osteoclasts
• low estrogen leads to more bone resorption than formation
• pushes bone closer to the fracture threshold

Question 17

What are some prevention strategies for osteoporosis?

Answer 17

Exercise (strength training, need load for increased bone formation), adequate calcium intake, maintain vitamin D levels, avoid heavy drinking, and don’t smoke.

Question 18

What are bisphosphonates used for?

Answer 18

Treat osteoporosis by binding to hydroxyapatite in bone, inhibiting osteoclast proliferation, and inducing osteoclast apoptosis.

Question 19

What are the side effects of bisphosphonates?

Answer 19

• musculoskeletal pain
• heartburn and ulcers
• osteonecrosis of the jaw
• side effects worsen with long term use

Question 20

What is hormone replacement therapy/estrogen replacement therapy?

Answer 20

• replacement of estrogen lost at menopause, for side effects of menopause (approved 1942) or osteoporosis (approved 1988)

Question 21

What controversies on HRT were pointed out by the Women’s Health Initiative?

Answer 21

• 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

Question 22

What are the benefits of hormone replacement therapy (HRT)?

Answer 22

Prevention of osteoporosis, alleviation of menopausal symptoms, cardioprotection if started before age 60, and overall reduced mortality rate

Question 23

What are the risks associated with hormone replacement therapy?

Answer 23

Potential coronary heart disease risk if started after age 60, and an increased risk of breast cancer depending on type of progesterone and SERMs

Question 24

What are SERMs?

Answer 24

selective estrogen receptor modulators

Question 25

Describe the male two cell model/HPG axis?

Answer 25

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

Question 26

What happens to testosterone with age?

Answer 26

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

Question 27

What is male hypogonadism?

Answer 27

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)

Question 28

What are the symptoms of male hypogonadism?

Answer 28

• fatigue and loss of energy
• low libido and erectile dysfunction
• reduced muscle mass
• increased fat mass
• osteoporosis

Question 29

What are the benefits of testosterone replacement therapy (TRT)?

Answer 29

Improves muscle mass and bone density, restores libido and erectile function, and alleviates other symptoms of hypogonadism.

Question 30

What are the risks of testosterone replacement therapy (TRT)?

Answer 30

• prostate cancer (depending on SARMs)
• cardiovascular disease or cardiovascular events

Question 31

Why is the term ‘andropause’ considered inaccurate?

Answer 31

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