Part 7:

Question 1

Non-hormonal signs of menopause (3):

Answer 1

1. variable cycle length.
2. skipped cycles.
3. amenorrhea.

Question 2

Menopause is characterized by how many months of amenorrhea?

Answer 2

12.

Question 3

Menopause hormonal signs (2):

Answer 3

1. decreased estrogen.
2. increased FSH:LH ratio.

Question 4

Menopause prior to age 40 is abnormal and classified as:

Answer 4

primary ovarian insufficiency.

Question 5

The decrease in E2 and inhibin B production in menopause is due to:

Answer 5

• severely limited number of growing follicles, which produce E2.

Question 6

The increase in FSH production in menopause is due to (2):

Answer 6

1. loss of E2 negative feedback.
2. decreased inhibition by Inhibin B.

Both E2 and Inhibin B are produced by growing GCs.

Question 7

Source and function of anti-Mullerian hormone (AMH) in reproductive-aged females:

Answer 7

• Source: granulosa cells within small growing follicles.
• Function: suppresses follicular recruitment via reducing young follicle FSH-sensitivity.

Question 8

What occurs to anti-Mullerian hormone (AMH) levels during the years leading up to menopause?

Answer 8

• decreases due to less granulosa cells within small growing follicles.

Question 9

What leads to an increase in recruitment and accelerated atresia/exhaustion of the follicular reserve (primordial cells) during the years leading up to menopause (2)?

Answer 9

• decreasing levels of anti-Mullerian hormone (AMH).
• increasing levels of FSH due to decreased E2 and inhibin B levels.

Question 10

Draw levels of E2 and FSH during the menopausal transition:

Answer 10

Question 11

With increasing maternal age, what birth risks increase (3)?

Answer 11

1. decreased chance of live birth; due to less viability of oocytes.
2. increased risk of maternal mortality.
3. increased risk of embryo aneuploidy.

Question 12

Risk factors that have to be evaluated prior to hormonal therapy (4)?

Answer 12

1. cardiovascular disease
2. thromboembolism
3. breast cancer
4. prior stroke or TIA

Question 13

E2-associated benefits in perimenopausal women include (3):

Answer 13

1. decreased cardiovascular risk.
2. bone density.
3. vasomotor control.

Question 14

Hormonal therapy for a woman with a uterus:

Answer 14

E2 + P4.

Question 15

Hormonal therapy for a woman without a uterus:

Answer 15

E2 only.

Question 16

Why is E2 + P4 hormonal therapy given to women with uteruses?

Answer 16

• E2 triggers proliferation and angiogenesis of endometrial tissue; cancer risk.
• High P4 levels downregulates P4-R and ERα expression in endometrium.

Question 17

Endometriosis is caused by:

Answer 17

• abnormal extra-uterine deposits of E2-responsive endometrial tissue.

Question 18

By which mechanism do endometrial fragments become deposited within the extrauterine environment?

Answer 18

retrograde menstruation.

Question 19

Extrauterine endometrial lesions most commonly form in which regions of the female anatomy (3)?

Answer 19

1. pelvic peritoneum.
2. ovaries.
3. rectovaginal septum.

Question 20

Symptoms of endometriosis include (3):

Answer 20

1. dysmenorrhea (painful periods).
2. dyspareunia (painful sex).
3. infertility.

Question 21

What genetic changes occur in the cells of extrauterine endometrial lesions (5)?

Answer 21

1. ability to evade immune destruction.
2. growth factors for neoangiogenesis.
3. nerve recruitment.
4. increased CYP19 (aromatase; increases E2 supply).
5. decreased progesterone receptors.

Question 22

How do cells of extrauterine endometrial lesions elevate local E2 levels?

Answer 22

1. express high levels of CYP19 (aromatase); E2 production favored.
2. express prostaglandins that promote increased CYP19 expression.

Question 23

What drugs can be utilized to decrease E2 levels in the setting of endometriosis, and why (4)?

Answer 23

1. GnRH agonists; alter GnRH pulsality.
2. Progestins; decrease LH>FSH secretion.
3. Aromatase inhibitors; decreases E2 production.
4. Androgens.

Question 24

Key diagnostic features of PCOS (2):

Answer 24

1. anovulation (amenorrhea or oligomenorrhea).
2. elevated androgens.

Question 25

Androgen-linked physcial symptoms of PCOS:

Answer 25

* hirsuitism * acne

Question 26

Congenital adrenal hyperplasia (CAH) is a disruption in adrenal cortical steroidogenesis due to:

Answer 26

21-hydroxylase enzyme mutation.

Question 27

Function of the enzyme 21-hydroxylase:

Answer 27

* required for cortisol and aldosterone production in the adrenal cortex.

Question 28

How can hyperandrogenemia result from a 21-hydroxylase enzyme mutation (CAH)?

Answer 28

* androgen precursor (DHEAS and androstenedione) steroidogenesis favored since only functioning cortical steroidogenic pathway. * Theca cells convert to testosterone; hyperandrogenemia results.

Question 29

How do increased circulating androgens (testosterone) lead to infertility?

Answer 29

1. testosterone converted to E2 via hypothalamic CYP19. 2. E2 binds to hypothalamic ERα receptors. 3. FSH \> LH secretion mainly blocked.

Question 30

How can HyperPRLemia and Cushing’s Syndrome cause infertility?

Answer 30

* Prolactin and cortisol both inhibit LH/FSH secretion.

Question 31

Body type of most women presenting with PCOS:

Answer 31

android obesity.

Question 32

The insulin model of PCOS:

Answer 32

1. increased abdominal fat leads to insulin resistance. 2. hyperglycemia occurs in response to insulin resistance. 3. hyperinsulinemia occurs due to hyperglycemia. 4. LH + insulin has a synergistic effect on Theca cell androgen production. 5. Hyperandrogenemia decreases LH/FSH secretion. 6. anovulation results due to decreased FSH levels.

Question 33

What molecule has a synergistic effect of LH-stimulated androgen production in Theca cells?

Answer 33

* insulin.

Question 34

LH model of PCOS:

Answer 34

1. Altered GnRH pulse generator firing frequency. 2. Excess LH secretion. 3. Hyperactivation of Theca cells; androgen production increased. 4. Hyperandrogenemia results. 5. Hyperandrogenemia decreases LH/FSH secretion. 6. Anovulation results due to decreased FSH levels.

Question 35

Effect of anovulation on LH levels:

Answer 35

1. No ovulation. 2. Very low progesterone production. 3. Large decrease in progesterone-mediated negative feedback on LH secretion. 4. Increased LH.

Question 36

Adrenal model of PCOS:

Answer 36

1. excess adrenal cortical androgen precursors (DHEAS and androstenedione). 2. steroid sulfatase in the ovaries converts DHEAS to DHEA. 3. Theca cells use DHEA and androstenedione to produce testosterone. 4. hyperandrogenemia results. 5. hyperandrogenemia decreases LH/FSH secretion. 6. anovulation results due to decreased FSH levels.

Question 37

Anabolic androgen steroids decrease levels of (4):

Answer 37

* sex-hormone binding protein (SHBG). * LH/FSH (negative feedback). * Testosterone. * Estrogen.

Question 38

Low sex-hormone binding protein (SHBG) = what testosterone levels?

Answer 38

high testosterone.

Question 39

High sex-hormone binding protein (SHBG) = what testosterone levels?

Answer 39

low testosterone.

Question 40

What enzyme levels are extremely elevated in CAH?

Answer 40

17α-hydroxyprogesterone.