female repro disorders

Question 1

1. Describe the anatomy and physiology of the reproductive axis in the female.

Answer 1

GnRH-induced LH signal in the female is dynamic. LH and FSH are equal for day 1-5 of follicular phase. During mid cycle, pulse generator speeds up and LH and FSH rise. During luteal phase, progesterone slows pulse resulting in infrequent high amplitude LH pulses and lower FSH levels

Question 2

which cells make estradiol vs androgens/ progesteron

Answer 2

Granulosa cells make estradiol and the luteal cells make the androgens: DHEA, androstenedione and testosterone, and also produce progesterone.

Question 3

Why are female ovaries more sensitive to toxic effects of chemo and radiation than testis

Answer 3

Progenitor cells are already committed to the primary follicle stage at birth

Question 4

functions of inhibin A and B

Answer 4

Inhibins inhibit FSH. the Inhibin A (α and ßA) is important in the luteal phase; the inhibin B (α and ßB) is active in the follicular phase of the menstrual cycle

Question 5

2. Describe and apply a general approach to disorders of the hypothalamic-pituitary-ovarian axis.

Answer 5

exclude pregnancy, Rule out an elevated prolactin, Androgen levels are usually not indicated in the absence of hirsutism and/or acne, A GnRH stimulation test is not helpful except in the evaluation children with precocious puberty, Draw LH and FSH levels in the first 5 days after menses starts: normally LH=FSH at that time. TSH, cortisol, IGF-1,

Question 6

hypogonadotropic hypogonadism labs

Answer 6

low LH, FSH and estradiol with amenorrhea

Question 7

Causes of hypogonadotropic hypogonadism

Answer 7

1. GnRH deficiency- Kallmans syndrome when associated with anosmia. 2. Hypothalamic amenorrhea- disorder of GnRH secretion (defects in amount or frequency) usually due to stress, exercise or poor nutrition. 3. Pituitary amenorrhea- prolactinoma, GH tumor, infiltrative dz (hemochromatosis, sarcoidosis, lymphocytic hypophysitis)

Question 8

treatment of stress induced hypothalamic amenorrhea

Answer 8

no treatment is option but bone loss occurs with subtle deficits in estrogen deficiency and as early as 6 months after onset

Question 9

Hypergonadotropic hypogonadism labs

Answer 9

High FSH and/or LH with low estradiol and amenorrhea

Question 10

Causes of Hypergonadotropic hypogonadism

Answer 10

1. Turners syndrome or gonadal dysgenesis (XO, XX/XO)- menopause before menarche. Require lifelong hormonal replacement. 2. Premature ovarian insufficiency- ovarian failure before 40. Autoimmune so look for other autoimmune dz, or srugical.

Question 11

Signs/Sx of early gonadal failure

Answer 11

irregular menses without molimal symptoms (breast tenderness, bloating and cramping that are signs of an ovulatory cycle). FSH levels rise before LH levels (due to loss of inhibin); there is often a waxing and waning course

Question 12

List the causes of hyperandrogenic anovulation

Answer 12

Congenital adrenal hyperplasia, PCOS, tumors causing hirsutism, obesity induced anovulation, prolactinoma, Cushings

Question 13

Attenuated congenital adrenal hyperplasia Sx, treatment

Answer 13

Hx of early pubarche, hirsutism, irregular menses. Family hx. Treatment: OCPs and spironolactone. Use to be glucocorticoids

Question 14

Polycystic ovarian syndrome Symptoms

Answer 14

begins in adolescence with irregular menses, anovulation, hirsutism and acne. 60% of patients are overweight but all are insulin resistant, and many have acanthosis nigicans

Question 15

PCOS labs

Answer 15

during day 1-5 of menstrual cycle: HIGH ratio of LH/FSH > 2.5/1, increased androgens, both testosterone (ovarian) and DHEAS (adrenal). Also, estrogen does not fluctuate throughout cycle as normally would. Low sex hormone binding globulin.

Question 16

PCOS etiology

Answer 16

GnRH pulse generator is turned up too high. Ovulation rarely occurs and progesterone levels don’t rise as they normally would in the luteal phase. Defect in ovarian steroidogenesis. Insulin resistance

Question 17

Risks associated with PCOS

Answer 17

risk of developing endometrial cancer due to the effect of estrogen unopposed by progesterone, as well as insulin resistance causing glucose intolerance and frank diabetes, hypertension and premature cardiac disease. Also central obesity, low HDL, high triglycerides,

Question 18

PCOS treatment

Answer 18

If no pregnancy desired: OCPs with nonandrogenic progestin or cyclic progesterone. Treat hirsutism with spironolcatone. Metformin for insulin resistance. If pregnancy desired: clomiphene citrate +/- metformin, Letrozole (aromatase inhibitor). Stop spironolactone 3 months before conception

Question 19

What kinds of tumors can cause hyperandrogenic anovulation

Answer 19

ovarian: sertoli-leydig cell, hilar cell, lipoid cell. Adrenal: adrenocortical adenoma or carcinoma, virilizing T secreting tumor (rare)

Question 20

Tumors causing hirsutism- clinical course

Answer 20

Patients with virilizing tumors of the ovary (makes testosterone) or adrenal (makes DHEA-S) are distinguishable from those with PCOS by the rapid onset and pace and the severity of the clinical symptoms, i.e. male pattern balding, hair on upper chest and back and clitorromegaly

Question 21

Virilizing tumors labs

Answer 21

Testosterone levels >200 ng/dl or DHEAS levels >800 ng/dl suggest TUMOR

Question 22

Obesity induced anovulation- clinical course and cause

Answer 22

Normal puberty until they exceed their weight set point. Then cycles become irregular, acne, hirsutism. US shows cysts in ovary secondary to anovulation. Excessive activity of aromatase and 5a-reductase in fat tissue.

Question 23

Obesity induced anovulation labs

Answer 23

In early follicular phase: normal and equal LH and FSH, with mild elevations in androgens

Question 24

Treatment of female hypogonadism

Answer 24

1. no treatment- stress induced hypothalamic amenorrhea. 2. Estrogen therapy. 3. Clomiphene citrate (Clomid). 4. Gonadotropin therapy. 5. Pulsatile GnRH.

Question 25

Use of estrogen therapy for hypogonadism

Answer 25

Birth control pills (BCPs) are used if contraception is an issue (BCP should have progestin without androgenic features if pt has acne and hirsutism). In congenital defects, low dose estrogens for 12-18 months to develop breast then add progesterone to differentiate ductules. Progesterone alone for dysfunctional uterine bleeding or hyperandrogenic anovulation if not estrogen deficient. In premature ovarian falure, estrogen and progesterone given similar to menopause therapy

Question 26

Use of clomiphene citrate for hypogonadism

Answer 26

Used if fertility is desired. It is a mixed estrogen agonist/antagonist that can augment folliculogenesis in patients in whom the GnRH pulse generator is not shut off completely. It fools the reproductive axis into thinking that there is estrogen deficiency. Gonadotropin levels, especially FSH levels rise, folliculogenesis improves and ovulation occurs.

Question 27

Clomid - when is it given and things to look for

Answer 27

Days 5-9 of menstrual cycle. Pt is monitored for anti-estrogen effects on cervical mucus and for rates of ovulation

Question 28

Use of gonadotropin therapy for hypogonadism

Answer 28

human menopausal gonadotropins (Pergonal) or recombinant FSH (Menotropin) and hCG (Profasi) are used to pharmacologically stimulate folliculogenesis and ovulation. Used for pts with hypothalamic amenorrhea who failed clomid or in prep for in vitro fertilization

Question 29

Gonadotropin therapy risks

Answer 29

hyperstimulation and multiple gestations

Question 30

Pulsatile GnRH therapy for hypogonadism

Answer 30

given to induce ovulation in women with hypothalamic amenorrhea to replace a deficient GnRH pulse generator. It requires intravenous administration with the use of a pump to successfully mimic the changes in the signal across the cycle

Question 31

Treatment of PCOS

Answer 31

Options include progesterone administration or a GnRH agonist (Lupron – given continuously it downregulates the GnRH receptors) for one month, to suppress endogenous GnRH, before Pergonal or pulsatile GnRH (by pump).insulin sensitizers such as metformin or the thiazoladinediones suppress androgens and improve ovulation rates in PCOS patients

Question 32

Treatment of premature ovarian failure

Answer 32

Oral contraceptives, cyclic E and P,donation of an egg from a relative or bank is now an option for fertility. Long-term estrogen replacement is indicated to protect bones and the cardiovascular system. Glucocorticoids possibly, FSH/LH and hCG possibly

Question 33

Benefits of hormone replacement in menopause

Answer 33

1. Brain: Central nervous system effects of estrogens and progestins, ?cognition 2. Bone: protection against fractures. 3. Cardiovascular: yes lipids, no stroke, MI. 4. GU: urinary frequency, dysparunia 5. Mood: ??

Question 34

Risks of hormone replacement in menopause

Answer 34

1. Cardiovascular: stroke MI, when given to women >20y pmp in combined regimen; ? primary vs secondary prevention vs risk. 2. Breast cancer: yes with daily conjugated estrogen and provera, not significant when conjugated estrogen alone. 3. Importance of dose response at different target tissues, genetic risks, formulations. 4. Additional investigation underway

Question 35

define premature menopause

Answer 35

cessation of menses before age 40

Question 36

What is polyglandular failure syndrome

Answer 36

Thyroid dz, ovarian failure, and addisons Dz (adrenal)