21: Amenorrhea

Question 1

Primary amenorrhea

Answer 1

absence of menarche by age 16 or 4 years after thelarche.

Question 2

Primary amenorrhea can be caused

Answer 2

(outflow tract abnormalities, end organ disorders, central disorders)
congenital abnormalities of the genital tract, chromosomal abnormalities, enzyme or hormonal deficiencies, gonadal agenesis, ovarian failure, or disruption of the hypothalamic–pituitary axis.

Question 3

The workup of primary amenorrhea is usually organized into four categories based on?

Answer 3

presence or absence of a uterus and the presence or absence of breast development.

Question 4

absence of both uterus and breasts, karyotype usually reveals ?
tests?

Answer 4

46,XY: males with steroid synthesis defects or varying degrees of gonadal dysgenesis/agenesis, in which adequate MIF is produced by gonadal tissue but androgen synthesis is insufficient
-karyotype analysis, followed by testosterone and FSH assays

Question 5

In the absence of a uterus and presence of breasts, ? will differentiate between

Answer 5

karyotype will ddx btw Müllerian agenesis/MRKH (XX) and testicular feminization/enzyme deficiency in testosterone synthesis (XY)

Question 6

In the absence of breasts and presence of a uterus ? will ddx btw ?

Answer 6

FSH will differentiate between hypergonadotropic (^FSH) and hypogonadotropic (low FSH) hypogonadism. Karyotype may be necessary to rule out gonadal agenesis in a 46,XY.

Question 7

Patients with both a uterus and breasts should be evaluated as if presenting with ?

Answer 7

secondary amenorrhea.

-other etiologies: disruption of H-P axis, congenital abnormalities of the genital tract

Question 8

Anatomic abnormalities including ? may lead to secondary amenorrhea. These patients fail to respond to ?

Answer 8

Asherman syndrome and cervical stenosis

estrogen and progesterone withdrawal

Question 9

high levels of ? is a common cause of secondary amenorrhea

Answer 9

prolaction (hyperprolactinemia)

Question 10

Patients with normal prolactin levels may be given a ? to investigate ?

Answer 10

progesterone challenge

adequacy of endogenous estrogen production and the outflow tract

Question 11

With progesterone challenge failure, the differential diagnosis becomes ? that can be differentiated by an ?.

Answer 11

hypergonadotropic or hypogonadotropic hypogonadism

FSH measurement

Question 12

tx of amenorrheic pts who are not seeking fertility vs those who are seeking fertility

Answer 12

not seeking fertility: tx specific cause and consider HRT if low estrogen
seeking fertility: ovulation induction, hyperprolactinemia require bromocriptine, other forms of hypogonadism: clomiphene and gonadotropins.

Question 13

Secondary amenorrhea

causes?

Answer 13

the absence of menses for 3 cycles or a total of 6 months in women who have previously had normal menstruation.
-pregnancy, anatomic abnormalities, ovarian dysfunction, prolactinoma and hyperprolactinemia, and CNS or hypothalamic disorders

Question 14

Testicular feminization, aka androgen insensitivity syndrome (AIS), results from ?

Answer 14

dysfunction or absence of the testosterone receptor that leads to a phenotypical female with 46,XY chromosomes

• (MIF) is secreted early in development, and these patients therefore have an absence of all Müllerian-derived structures
• have undescended testes, breasts, primary amenorrhea, no uterus, vagina with blind pouch, sterile

Question 15

Primary ovarian failure results in low levels of ? but elevated levels of ? termed ?

Answer 15

low estradiol
high gonadotropins

hypergonadotropic hypogonadism

Question 16

Savage syndrome

Answer 16

failure of the ovaries to respond to FSH and LH secondary to a receptor defect

Question 17

Turner syndrome

Answer 17

(45,XO), the ovaries undergo such rapid atresia that by puberty there are usually no primordial oocytes

Question 18

Defects in the enzymes involved in steroid biosynthesis, particularly ?, can result in ?

Answer 18

17-hydroxylase

amenorrhea and absence of breast development given the lack of estradiol.

Question 19

Swyer syndrome

Answer 19

congenital absence of the testes in a genotypical male
(similar to ovarian a genesis)
testes never develop, so MIF is not released and these patients have both internal and external female genitalia but no estrogen so no breast development

Question 20

Kallmann syndrome

Answer 20

hypogonadotropic hypogonadism, congenital absence of GnRH and is commonly associated with anosmia

Question 21

Other ways that GnRH transport may be disrupted

Answer 21

compression or destruction of the pituitary stalk or arcuate nucleus
-can result from tumor mass effect, trauma, sarcoidosis, tuberculosis, irradiation, or Hand-Schuller-Christian disease.

Question 22

here may be defects in GnRH pulsatility in cases of ?

Answer 22

anorexia nervosa, extreme stress, athletics, hyperprolactinemia, hypothyroidism, rapid or severe weight loss, and constitutionally delayed puberty.

Question 23

treatment of hypergonadotropic vs hypogonadotropic hypogonadism

Answer 23

hyper: often have irreversible ovarian failure and will require ERT
hypo: require further workup as patients with secondary amenorrhea

Question 24

Asherman syndrome

etiologies?

Answer 24

presence of intrauterine synechiae or adhesions, usually secondary to intrauterine surgery or infection.
-D/C, myomectomy, C section, endometritis

Question 25

ovarian failure may be due to ?

how to treat ?

Answer 25

• ovarian torsion, surgery, infection, radiation, or chemo
• Premature ovarian failure (POF): menopause occurs without another etiology before age 40, it is considered POF. Before age 35, chromosomal analysis is usually performed
• tx with supplemental estrogen to decrease risk CV disease and osteoporosis

Question 26

Polycystic ovary syndrome (PCOS), aka ?

diagnosed with 2/3 of the following:

Answer 26

Stein-Leventhal syndrome
oligo or anovulation, clinical or laboratory evidence of hyperandrogenism (hirsutism, male balding, acne), and polycystic ovaries on US

Question 27

in the case of PCOS, chronic anovulation leads to elevated levels of ? which leads to ?

Answer 27

estrogen and androgen leads to increased LH:FSH ratio, atypical follicular development, anovulation, and increased androgen production
-may develop develop insulin resistance and hyperinsulinemia, T2DM

Question 28

In PCOS patients desiring pregnancy, ovulation induction may be performed using ?
ovulation can be significantly increased by ?

Answer 28

clomiphene citrate (Clomid) (acts as an antiestrogen to stimulate gonadotropin release)
weight loss

Question 29

In PCOS patients with hyperinsulinemia and insulin resistance, ? may increase spontaneous ovulation, and in the least will improve insulin resistance and may help with weight loss

Answer 29

metformin

Question 30

For patients who are not currently interested in fertility, the goal of therapy is ? with ?

Answer 30

menstrual cycle control.

• combo OCPs will assist in cycle regulation and reduce risk of endometrial hyperplasia or carcinoma, and also may improve symptoms of acne and arrest further development of hirsutism by decreasing circulating levels of androgens
• progestin therapy alone in the form of a levonorgestrel IUD, oral pills (Provera), or injectable medications (Depo-Provera) will similarly decrease their risk of endometrial disease

Question 31

PCOS pts have increased risk of

Answer 31

HTN, OSA, CAD, T2DM, insulin resistance

Question 32

Prolactin release is inhibited by ? and stimulated by ?

Answer 32

dopamine

serotonin and thyrotropin-releasing hormone (TRH)

Question 33

etiologies of hyperprolactinemia

Answer 33

prolactinoma, hypothyroidism, idiopathic,
Drug-induced, Interruption of H-P relationship, Pituitary stalk section, Peripheral neural stimulation, Nipple stimulation, Spinal cord lesion, CNS disease

Question 34

drugs that can induce hyperprolactinemia

Answer 34

dopamine antagonists (Haldol, Reglan, phenothiazine), TCAs, estrogen, monoamine oxidase (MAO) inhibitors, and opiates

Question 35

secondary amenorrhea work up

Answer 35

B-hCG, H/P focused on s/s of hypothyroidism, hyperprolactinemia, hyperandrogenism, get TSH, prolactin levels

Question 36

if PRL elevated check

Answer 36

med list, visual fields, CNs, breast exam, MRI to r/o H-P lesion

Question 37

if progesterone challenge positive (+ w.drawal bleeding), amenorrhea is usually secondary to ?

Answer 37

anovulation, which can be caused by a variety of endocrine disorders that alter pituitary/gonadal feedback such as polycystic ovaries, tumors of the ovary and adrenals, Cushing syndrome, thyroid disorders, and adult-onset adrenal hyperplasia
-treat with OCPs

Question 38

if progesterone challenge negative, must evaluate with ?
if still no bleeding, suspect ?
if bleeding suspect ? next step?

Answer 38

• estrogen and progesterone administration
• outflow tract disorder such as Asherman syndrome or cervical stenosis
• suggests an intact and functional uterus without adequate endogenous estrogen stimulation–>Measure of FSH and LH to ddx btw a H-P disorder (low/normal FSH and LH levels under 40) and ovarian failure (high FSH and LH levels over 40)
• consider HRT/OCPs

Question 39

For patients who do not respond to Clomid, ? can be used to stimulate ovulation.
make sure to monitor gonadotropin ovulation induction with US and estradiol levels due to risk of ?

Answer 39

human menopausal gonadotropin (hMG) or recombinant GnRH

ovarian hyperstimulation