Female Repro Physio (Day 3 - Intervention)

Question 1

What neurotransmitter is known to inhibit Prolactin (PRL) secretion from the anterior pituitary?

Answer 1

Dopamine lowers PRL secretion

Question 2

What roles do Estrogens and Progesterone play in lactation or milk let-down during pregnancy?

Answer 2

Estrogens and Progesterone inhibit milk-let down during gestation. They activate stimulate development of breast ductal epithelium and breast alveoli.

Question 3

After birth, estrogen and progesterone levels are ______. Infant suckling stimulates secretion of ____ and _____; while inhibiting secretion of ______.

Answer 3

Post-partum, E2 and P4 are at LOW levels. Suckling raises PRL (lactation) and Oxytocin (milk let-down); while lowering GnRH levels to stop the cycling.

Question 4

What condition is Hyperprolactinemia linked to and why?

Answer 4

High levels of PRL is correlates to infertility because that hormone inhibits the release of gonadotropins which are necessary for menstrual cycles. This is a physiologic condition that occurs in nursing mothers.

Question 5

Menopause is a normal consequence of _____. If this occurs prior to age ____, it is pathologic. What medical condition is associated with this?

Answer 5

Aging >51 years;

Prior to age 40 is pathological, linked to Ovarian (Failure) Insufficiency.

Question 6

Why would AMH be measured in someone who is concerned about infertility? What secretes it in the human body?

Answer 6

Antimullerian hormone (AMH) is a marker of fertility. Since normal levels are an indication of how many healthy growing follicles will be recruited per cycle, if these levels are lower than normal that may indicate lower fertility.

Question 7

What are the expected levels of FSH, AMH, Estrogen and follicular reserve for a middle aged woman at menopause? How many follicles are left at this period of life?

Answer 7

Elevated FSH, Reduced AMH, Low E2 and Decreased Follicular reserve are indicators of menopause. At this time of life, there are around 1000 follicles left per ovary.

Question 8

Around what age might a woman experience peak fertility? Why is this the case?

Answer 8

Peak fertility occurs at the overlap of max AMH and high follicular recruitment levels. This occurs at around the late 20s for an ovulating female.

Question 9

Menopausal signs and symptoms prior to age 40 is classified as ___________.

Answer 9

Primary ovarian insufficiency (premature ovarian failure) characterized by low E2 and elevated FSH in a younger woman.

Question 10

What enables Granulosa cells (GC) to make estrogen?

Answer 10

Androgens from Theca cells (mainly Testosterone) are converted into estrogen by GC via CYP19 (aromatase) enzyme.

Question 11

What are 3 things that growing follicles secrete during the menopausal transition and what are their effects?

Answer 11

1. AMH - inhibits follicular recruitment
2. E2 = inhibits FSH
3. Inhibin B = secreted by granulosa cells to inhibit FSH

Question 12

Describe the mechanism that results in elevated FSH levels at menopause.

Answer 12

Diminished follicular reserve results in less Inhibin B and E2 being secreted. This loss of negative feedback raises FSH levels to further accelerate the loss of the follicular reserve.

Question 13

Describe the significance of in vitro fertilization (IVF) as an assisted reproductive technology for women older than age 35.

Answer 13

IVF technology can be used to increase the likelihood of a live birth in women older than 35. It’s better for women at this age to receive recipient oocytes from donors rather than preserve their own from earlier.

Question 14

From the point plot in lecture, what is lost with age, pertaining to female reproductive viability: Oocyte quality, ovarian function or uterine receptivity?

Answer 14

Oocyte quality and ovarian function are physiologically lost with age. The older the woman (>35), the less fertile she is, putting her at risk of ovarian insufficiency. Uterine receptivity most likely is not affected.

Question 15

What is another feasible ART intervention that can be used to increase the likelihood of live birth success in less fertile women?

Answer 15

Cryopreservation of oocytes that were saved at an earlier point in life may be a feasible option. Oocytes retrieved <36 y.o.a have a 10% live birth success compared to >36 y.o.a with a 3% live birth success.

Question 16

2 risks associated with pregnancy for a woman of advanced maternal age are…

Answer 16

1. Embryo aneuploidy - chromosomal defects from lower quality of female oocytes
2. Maternal mortality

Question 17

A physician prescribes E2 and P4 as symptom relief for a peri-menopausal woman (with a uterus) experiencing hot flushes. Why didn’t she apply just E2? What significance does this therapy hold for younger menopausal women?

Answer 17

P4 prevents the unchallenged E2 from developing into endometrial cancer. Hormone replacement therapy is more advisable for a minimal time in younger menopausal women to assist with the transition.

Question 18

List at least 3 exclusionary factors that would have a doctor not prescribe the E2/P4 hormonal therapy to treat hot flushes.

Answer 18

1. History of stroke or TIA
2. Breast Cancer
3. Elevated venous thromboembolism (VTE = tendency to make clots)
4. Cardiovascular disease

Question 19

When the minimal threshold of healthy growing follicles is reached, hypothalamic-pituitary-ovarian feedback loops are _________. This has FSH levels ____ and E2 levels ______. This results in __________ cycles.

Answer 19

At menopause, HPA feedback loop is disrupted;
FSH rises + E2 declines;
Results in missed or variable cycles.

Question 20

Name some signs/symptoms that a physician can use to diagnose PCOS.

Answer 20

History of irregular menstrual cycles;

anovulation; hyperandrogenemia (high ovarian androgens such as testosterone); Hyperinsulinemia

Question 21

Describe the key feature(s) that can be seen using ultrasonography to differentiate PCOS ovaries from normal ones.

Answer 21

HUGE cystic follicles seen as abnormally-large, black circles within the US image of the ovary. The affected ovary features 12 or more antral follicles 2-9 mm in diameter.

Question 22

Insulin, when paired with LH, has a _________ effect on theca cells’ production of __________. In PCOS, this presents as _________.

Answer 22

Insulin + LH has a SYNERGISTIC effect on Testosterone secretion from theca cells. This presents as Hyperandrogenemia.

Question 23

Why would Hyperandrogenemia inhibit ovulation? Describe the mechanism.

Answer 23

Answer: Negative Feedback.
Mech: Testosterone is aromatized to E2 via Granulosa Cells’ CYP19. Excess amounts of estrogen inhibit GnRH release which lowers FSH/LH secretion. This ultimately leads to no ovulation from the dominant follicle.

Question 24

List at least 5 risk factors linked with increased morbidity of PCOS.

Answer 24

1. Diabetes Mellitus II
2. Cardiovascular Disease
3. Resistant HTN
4. High risk of Endometrial Cancer (unchallenged E2)
5. Obstructive Sleep Apnea (from visceral fat)

Question 25

List 3 phenotypic changes of PCOS. What causes these changes?

Answer 25

High levels of testosterone can lead to more secondary male characteristics for a young woman with PCOS. This includes Acne, deepened voice, male patterned baldness and Hirsutism (hair on chest and or face).

Question 26

What are the 2 overlapping syndromes of metabolic obesity between DM II, PCOS and Metabolic Syndrome?

Answer 26

1. Truncal obesity

2. Insulin Resistance

Question 27

Why are young women with PCOS at a higher risk of developing Endometrial cancer?

Answer 27

Elevated E2 without accompanying Progesterone = “Unchallenged Estrogen” that is bad for the endometrium (can cause over-proliferation).

Question 28

Elevated intrfollicular androgen (testosterone) levels promote ______ _______.

Answer 28

Follicular dysgenesis (sometimes cystic follicles occur). Cystic follicles are not mutually exclusive to PCOS.

Question 29

What aspects about LH secretion changes in hyperandrogenemic anovulatory women (PCOS)?

Answer 29

Amplitude and frequency increases for LH secretion. This happens because there is no progesterone to act as negative feedback to its secretion.

Question 30

List the order of priority for treatment options for PCOS. Explain why each is valid.

Answer 30

1. Birth control pills - E2/P4 has a negative feedback “rebooting” effect @ HPO axis. It decreases LH and androgen levels.
2. Metformin - combat insulin resistance and hyperglycemia, especially if weight loss is unsuccessful and blood sugar remains elevated.
3. Spironolactone - androgen antagonist will reduce levels of testosterone.

Question 31

What does a high FSH:LH ratio indicate for a healthy middle aged woman?

Answer 31

Menopause as there is less E2-negative feedback on FSH at this time of life.

Question 32

What might a high LH:FSH ratio indicate in a woman at reproductive age?

Answer 32

Polycystic Ovarian Syndrome (PCOS) since there is less FSH.

Question 33

In an otherwise healthy woman of reproductive age, what is the rule of thumb for conducting diagnostic measures if she has infertility?

Answer 33

Measure hCG and Basal Body Temperature to rule out pregnancy. It’s recommended to start out simple then course through the more expensive/invasive tests.

Question 34

At day 21 of the menstrual cycle in a healthy non-pregnant woman, Progesterone should be at _____ levels.

Answer 34

Relatively low levels since progesterone is starting to build up from the corpus luteum.

Question 35

What effect does Clomiphene (an ER-alpha antagonist) have on the following? (E2, GnRH, FSH, menstrual cycles)

Answer 35

E2 decreases, GnRH increases, FSH increases, Frequency of Cycles increases

Question 36

What is the best treatment option to alleviate the night sweats and concerns of osteoporosis for a middle-aged woman, with a family history of Breast cancer? Why?

Answer 36

Calcitriol and Calcium supplement. It’s best to avoid E2/P4 because of the cancer History.

Question 37

What can explain the presence of High Estrogens in a 25-year-old woman with PCOS (assume she has an elevated waist to hip ratio)?

Answer 37

Androgen Aromatization occuring within the peripheral fat is converting the high level of androgens into estrogens via CYP19.