Female Reproductive Endocrinology V

Question 1

Recall that peripheral fat expresses CYP19; thus this tissue can utilize the abundance of androstenedione and testosterone for the production of

Answer 1

Estrone (E1) and E2 respectively

Question 2

Mildly, but chronically elevated E2 (generally in the mid-follicular phase range) with an increased E1: E2 ratio is common in

Answer 2

PCOS

Question 3

These estrogens with elevated testosterone exert negative feedback on

Answer 3

FSH secretion

Question 4

Many endocrine tissues can purportedly feed into PCOS, and these include the

Answer 4

Ovary, adrenal. and HPA

Question 5

There are several genetic links coupled to PCOS inducing disruptions in

Answer 5

1. ) Insulin sensitivty
2. ) Androgen production
3. ) Gonadotropin secretion

Question 6

Regarding gonadotropin secretion and PCOS, an abnormally elevated GnRH pulse frequency is not uncommon, and this leads to an increase in

Answer 6

LH secretion while impairing FSH secretion

Question 7

Recall that LH stimulates theca cell androgen production; and interestingly, insulin has a synergistic effect of

Answer 7

LH-stimulated androgen synthesis in theca cells

Question 8

Androgen production (notably testosterone) is driven above that which occurs in normal ovaries with

Answer 8

Excess LH and slightly elevated Insulin

Question 9

Of note is that abdominal obesity exacerbates many symptoms that can manifest during

Answer 9

PCOS

Question 10

Glucose intolerance, insulin resistance, hyperandrogenemia, and others are examples of

Answer 10

Symptoms that we can see in PCOS

Question 11

It should be mentioned that insulin resistance is essentially universal in the case of PCOS women with a body-mass index of

Answer 11

Greater than 30

Question 12

How can we find BMI?

Answer 12

BMI = Weight (kg) / Height (m^2)

Question 13

There is overlap in many of the symptoms of PCOS with those describing the

Answer 13

Metabolic syndrome

Question 14

To summarize, the more “typical” PCOS phenotype is one of

Answer 14

Overweight w/ abdominal obesity, anovulation, and hyperandrogenism

Question 15

First and foremost in the management of PCOS in overweight women is weight loss since this can reverse

Answer 15

Insulin resistance and hyperandrogenism

Question 16

Has been correlated with restored ovulatory function and reduction in androgens in some PCOS women

Answer 16

Weight loss of 2-7%

Question 17

Because of its effectiveness, lifestyle modifications should be considered as a first course of action in

Answer 17

Overweight PCOS women

Question 18

Can help to normalize menstrual cyclicity and reduce any incidence of endometrial hyperplasia due to unopposed E2 seen in PCOS

Answer 18

The use of OCPs

Question 19

A GnRH agonist which can assist in restoring normal gonadotropin secretion

Answer 19

Clomiphene

Question 20

An insulin-sensitizing drug qhich by normalizing insulin responsiveness can assist in restoring ovulation

Answer 20

Metformin

Question 21

Can aid in reversing hirsutism

-not commonly used

Answer 21

Antiandrogens (flutamide)

Question 22

FSH (rFSH) can be used, but this technique is not routine since it can induce

Answer 22

Ovarian hyperstimulation syndrome

Question 23

Following an rFSH regimine, we can also see an increased risk of

Answer 23

Multiple-fetus pregnancies

Question 24

Can be used in the event of elevated DHEAS in PCOS women

Answer 24

Exogenous glucocorticoids

Question 25

The neuroendocrine system is made up of the

Answer 25

Hypothalamus and pituitary

Question 26

Often occurs at the cellular/molecular level as a result of acute and/or chronic over-stimulation by a hormone

Answer 26

Desensitization

Question 27

Desensitization often works as a cellular failsafe system that prevents sustained

Answer 27

Hyperstimulation

Question 28

When the hormone affects the cell population from which it is released

Answer 28

Autocrine function

Question 29

When the hormone affects a neighboring population of different cells; without requiring the circulatory system as a vehicle

Answer 29

Paracrine function

Question 30

Use of the circulatory system to affect a target tissue

Answer 30

Endocrine function

Question 31

The genes for many protein hormones encode for the transcription and translation of immature (inactive) precursor hormone molecules known as

Answer 31

Pre-hormones or prohormones

Question 32

Often required in order for the mature hormone to be identified for secretion by the Golgi apparatus

Answer 32

Post-translational modifications

Question 33

Peripheral fat tissue, the brain/neural, heart, liver, and many other tissues possess some

Answer 33

Steroidogenic function

Question 34

Rely upon the physiology of positive feedback or feed forward

Answer 34

Stimulation tests

Question 35

One example of a stimulation test uses the physiology controlling the secretion of gonadotropin-releasing hormone (GnRH) and its stimulation of the

Answer 35

Gonadotropins

Question 36

During puberty, the hypothalamic hormone GnRH stimulates the secretion LH and FSH from the

Answer 36

Anterior pituitary

Question 37

Prior to puberty, has little effect on gonadotropin secretion

Answer 37

GnRH

Question 38

This endogenous mechanism is useful in the diagnosis of precocious puberty, and is the basis of the

Answer 38

GnRH stimulation test

Question 39

A child with signs and symptoms of precocious puberty can be given a dose of GnRH, and later, blood is drawn in order to measure

Answer 39

LH

Question 40

An elevation in LH above the reference standard for the child’s age and gender would indicate that

Answer 40

His/her pituitary has been prematurely activated

Question 41

This leads to the diagnosis of

Answer 41

Central (neuroendocrine) precocious puberty

Question 42

What are 5 other stimulation tests?

Answer 42

1. ) ACTH 2. ) CRH 3. ) GH 4. ) TRH 5. ) OGTT

Question 43

Rely upon the physiology of negative feedback or some direct suppression of an endocrine system

Answer 43

Suppression tests

Question 44

ACTH is down regulated by

Answer 44

Cortisol

Question 45

TSH in down-regulated by

Answer 45

Thyroid hormones

Question 46

Gonadotropins are down-regulated by

Answer 46

Gonadal steroid hormones estradiol-17B, testosterone, and progesterone

Question 47

Growth hormone is down-regulated by

Answer 47

Hyperglycemia

Question 48

Aldosterone is down-regulated by an

Answer 48

Oral salt load

Question 49

One classic example where physiology was instrumental in evaluating endocrine function was in the use the

Answer 49

Dexamethasone (Dex) suppression test

Question 50

The dex suppression test was based upon the physiology of cortisol-dependent negative feedback on

Answer 50

ACTH secretion

Question 51

An extremely potent pharmacological derivative of Cortisol

Answer 51

Dex

Question 52

This test was thus used to diagnose

Answer 52

Hypercortisolism (Cushing's disease and Cushing's syndrome)

Question 53

Hypercortisolism driven by excess ACTH of pituitary origin; e.g., a pituitary adenoma

Answer 53

Cushing's Disease

Question 54

In patients with Cushing’s disease, feedback inhibition \ upon ACTH by cortisol is reset to a much higher threshold. In this case, a high enough dose of dex suppresses

Answer 54

ACTH and cortisol

Question 55

Certain tumors can also secrete ACTH, and some of these neoplasms are not subject to negative feedback by

Answer 55

Dex

Question 56

Thus, if a patient has Cushing’s syndrome due to ectopic production of ACTH, the high dose dex suppression test may have little if any effect on

Answer 56

ACTH or cortisol levels

Question 57

In today’s world there are more direct methods to evaluate the presence and etiology of cortisol excess. Most commonly we measure

Answer 57

Salivary or urine free cortisol