Amenorrhea

Question 1

Cryptomenorrhea

Answer 1

is another condition caused by anatomic disorders interfering with the outflow of menses, such as an imperforate hymen or transverse vaginal septum, although these women are actually menstruating.

Question 2

Primary amenorrhea

Answer 2

is defined as the absence of menses in a woman who has never menstruated by the age of 15 years, Another definition includes girls who have not menstruated within 5 years of breast development, if occurring by age 10. Breast development (thelarche) should occur by age 13 or otherwise requires evaluation as well.

Question 3

The incidence of primary amenorrhea is

Answer 3

less than 0.1%.

Question 4

Curettage for a missed abortion results in a high incidence of IUA formation (30%).

Answer 4

Intrauterine adhesions (IUAs) or synechiae (Asherman syndrome) can obliterate the endometrial cavity and produce secondary amenorrhea. Rarely, a missed abortion or endometrial tuberculosis can also cause endometrial destruction.

Question 5

Central Nervous System Structural Abnormalities causes of amenorrhea

Answer 5

Hypothalamic lesions include craniopharyngiomas, granulomatous disease (e.g., tuberculosis, sarcoidosis), and sequelae of encephalitis. When such uncommon lesions are present, circulating gonadotropins and E2 levels are low, and withdrawal uterine bleeding will not occur after progestogen administration.

Question 6

Drugs causes amenorrhea

Answer 6

Drugs

Phenothiazine derivatives, certain antihypertensive agents,

Question 7

Type 2 DM is more prevalent (—to —- times higher) in women with PCOS of reproductive age

Answer 7

Type 2 DM is more prevalent (3 to 5 times higher) in women with PCOS of reproductive age.

Question 8

Treatment of PCOS

Answer 8

If the complain is Menstrual irregularities:

• OCPs: good for hirsutism and cases of Insulin resistance
• POP:medroxyprogestrone acetate 5-10 mg or norethindrone acetate 2.5 -10mg

If subfertility: 1st line: letrozole (2.5-5mg/day, 5 days)- CC +/- metformin
2nd line: low-dose gonadotropins- pulsatile GnRH (ovarian diathermy or drilling?)
letrozole superior to CC but has advantage of less risk of multiple pregnancy

Question 9

Amenorrhea can be classified by Functional Compartments The reproductive axis can be divided into the functional compartments:

Answer 9

1-Outflow: uterus, cervix and vagina
2- Gonadal: ovaries
3-anterior pituitary gland
4- hypothalamus

Question 10

There are three types of Functional hypothalamic amenorrhea (FHA)

Answer 10

weight loss-related, stress-related, and exercise-related amenorrhea.

Question 11

leuprolide stimulation test,

Answer 11

may be used to evaluate abnormal pubertal development

Question 12

Among women with PCOS, up to -% of those who are obese develop impaired glucose tolerance “prediabetes” by age 40, while up to -% of obese women develop type 2 diabetes.

Answer 12

Among women with PCOS, up to 35% of those who are obese develop impaired glucose tolerance “prediabetes” by age 40, while up to 10% of obese women develop type 2 diabetes.

Question 13

Ddx of PCOS

Answer 13

• ovarian hyperthecosis
• congenital adrenal hyperplasia (late-onset)
• patients with menstrual disturbances and signs of hyperandrogenism
• idiopathic hirsutism, Familial hirsutism
• masculinising tumours of the adrenal gland or ovary (rapid onset of signs of virilization)
• Cushing syndrome(low K+, striae, central obesity, high cortisol, high androgens in adrenal Ca)
• hyperprolactinemia
• exogenous anabolic steroid use
• stromal hyperthecosis (valporic acid)
• drugs (e.g. Danazol, androgenic progestins)
• hypothyroidism

Question 14

Obstetrical complications of women with PCOS

Answer 14

Increased risk GDM
Preeclampsia
Caesarean section
Preterm/postterm delivery

Question 15

Secondary Amenorrhea defined as

Answer 15

3 months Without Cycle if regular

Or 6 months if irregular

Question 16

is a form of gonadal dysgenesis. The genetic sex of the affected individual is 46,XY, and at birth the neonate is phenotypically female and does not appear to have any sexual ambiguity.

Answer 16

Swyer syndrome
Approximately 10–20% of cases are a result of SRY gene mutations. Other genes, such as SF1, WT1, and DAX1, are possible candidates in the interference of sex determination.

Question 17

Perrault syndrome

Answer 17

(46,XX; gonadal dysgenesis and sensorineural deafness)

Question 18

Swyer syndrome karyotype and pathogenesis

Answer 18

(46,XY; gonadal dysgenesis)

Question 19

Diagnosis of Cushing Syndrome

Answer 19

A recent meta-analysis commissioned by the Endocrine Society Diagnosis of Cushing Syndrome Task Force found similar accuracy for such tests as 24-hour urine cortisol, 1-mg overnight dexamethasone suppression test, serum or salivary midnight cortisol, and combined strategies based on these tests.
Dexamethasone at a dose of 1 mg is given orally at 11:00 pm and a plasma cortisol level is drawn at 8:00 am the next morning. A value of less than 5 micrograms/dL rules out Cushing syndrome

Question 20

The current guidelines published by the Endocrine Society recommend against the use of tests for random serum cortisol or plasma ACTH levels and urinary 17-ketosteroids, pituitary and adrenal imaging, and the 8-mg dexamethasone suppression test as first-line tests for the diagnosis of Cushing syndrome.

Answer 20

In the presence of a basal level ACTH less than 5 micrograms/mL, a highdose dexamethasone suppression (taking 2 mg every 6 hours for 2 consecutive days), and no decrease in urinary steroids (17-hydroxysteroid and cortisol) by at least 40%, an adrenal tumor is likely. When ACTH is measurable in the blood (greater than 20 pg/mL), an ectopic ACTH-producing tumor is unlikely if the urinary steroids decrease by at least 40%.

Question 21

Cushing disease Vs. Cushing syndrome

Answer 21

Cushing disease is present when an ACTH and a chest X-ray are normal and an abnormal sella is found on computed tomography scan of the pituitary gland.

Question 22

17-hydroxyprogesterone level is used as a screening test for

Answer 22

21-hydroxylase deficiency
A screening 17-hydroxyprogesterone level greater than 200 ng/dL requires an adrenocorticotropic hormone stimulation test for further evaluation of adultonset CAH. A screening 17-hydroxyprogesterone level of 800 ng/dL does not require further testing.

Question 23

the best screening test to confirm the diagnosis of cushing syndrome is

Answer 23

overnight dexamethasone suppression test.

Question 24

Laboratory findings suggestive of an ovarian androgen-producing tumor include

Answer 24

a total testosterone level greater than 200 ng/dL and a reversal in the androstenedione-to-testosterone ratio.

Question 25

Androgen insensitivity syndrome (AIS) also referred to as Reifenstein syndrome.

Answer 25

involves a muta-tion of the androgen receptor located on chromosome Xq11-12, resulting in complete loss of function (CAIS) or partial loss of function (PAIS).

Question 26

The causes of primary ovarian insufficiency include

Answer 26

genetic abnormalities of the X chromosome (eg, 45,X and fragile X premutations), enzyme defects such as 17α-hydroxylase deficiency, aromatase deficiency, or galactosemia. Other etiologies include chemotherapy, radiation, viral infection, autoimmune disorders, and unknown causes.

Question 27

expansion of the CGG tandem repeat on the X chromosome in a region that has been named the fragile X mental retardation 1 (FMR1) gene

Answer 27

Fragile X syndrome
Women with infertility due to primary ovarian insufficiency who have a normal karyotype should be tested for the fragile X premutation.

Question 28

Women who have not resumed menstrual function within 6 months of stopping OC use should be evaluated for secondary amenorrhea.

Answer 28

Waiting more than 6 months before initiation of a formal evaluation would delay diagnosis and treatment of her amenorrhea.

Question 29

The criterion standard for confirming the diagnosis of nonclassic CAH is

Answer 29

the ACTH (cosyntropin) stimulation test. Baseline 17α-hydroxyprogesterone is drawn in the morning at any time during the menstrual cycle; ACTH (cosyntropin) 250 micrograms is administered intravenously as a bolus over a minute. A blood sample for 17α-hydroxyprogesterone is drawn 60 minutes after ACTH is given. In most patients with nonclassic CAH, stimulated 17α-hydroxyprogesterone levels will be in excess of 1,500 ng/dL at 1 hour.

Question 30

The two most common causes of gestational hyperandrogenism

Answer 30

1) luteomas of pregnancy and 2) hyperreactio luteinalis.

Question 31

magnetic resonance imaging and ultrasonography show the ovaries to have a characteristic spoke-wheel appearance, representing compressed echogenic stroma surrounding multiple simple or minimally hemorrhagic cysts without solid elements, dx ?

Answer 31

Hyperreactio luteinalis

Question 32

When Biopsy of the endometrium should be considered in pcos patients

Answer 32

older than 35 years with unopposed estrogen production and amenorrhea that exceeds 12 months.

Question 33

with PCOS have an approximately ?-fold increased risk of endometrial cancer,

Answer 33

with PCOS have an approximately 2.7-fold increased risk of endometrial cancer,

Question 34

Amenorrhea Evaluation is considered for an adolescent:

Answer 34

(1) who has not menstruated by age 15 or within 3 years of thelarche or (2) has not menstruated by age 14 and shows signs of hirsutism, excessive exercise, or eating disorder (American College of Obstetrician and Gynecologists, 2017 d).

Question 35

Secondary amenorrhea Definition

Answer 35

amenorrhea for 3 months or fewer than nine cycles per year to be investigated (American Society for Reproductive Medicine, 2008; Klein, 2013).

Question 36

POI is defined as

Answer 36

loss of oocytes and the surrounding support cells prior to age 40 years.

Question 37

The diagnosis of POI is determined by

Answer 37

two serum FSH levels that measure greater than a threshold range of 30 to 40 miU/mL and are obtained at least 1 month apart. This definition distinguishes POI from the physiologic loss of ovarian function, which occurs with normal menopause. The incidence of POI has been estimated at 1 in 1000 women younger than 30 years and at 1 in 100 women younger than 40 (Coulam, 1986).

Question 38

the most frequent cause of POI is

Answer 38

Gonadal dysgenesis

Question 39

Diagnosis? Patients with a 46,XY genotype and gonadal dysgenesis are phenotypically female due to absent testosterone and absent antimiillerian hormone (AMH) secretion by dysgc:netic testes.

Answer 39

(Swyer syndrome)

Question 40

in some cases of gonadal dysgenesis, a Y chromosome is prcsent.lfY chromosomal material is found, the streak gonads are remo’Vl:d because nearly 25 percent of these patients will develop a malignant germ cell tumor

Answer 40

Thus, chromosomal analysis is performed in all cases of amenorrhea associated with POI, particu· larly bcrore age 30. The presence of a Y chromosome cannot be determined clinically, as only a few patients will demonstrate signs of androgen o:.a:ss.

Question 41

This syndrome is caused by a triple repeat sequence mutation in the X-linked FMR1, The fully expanded mutation (> 200 CGG repeats) becomes hypermethylated, resulting in silencing of gene expression.

Answer 41

fragile X syndrome

Question 42

This syndrome is caused by a triple repeat sequence mutation in the X-linked FMR1, The fully expanded mutation (> 200 CGG repeats) becomes hypermethylated, resulting in silencing of gene expression.

Answer 42

fragile X syndrome

Question 43

this fully expanded mutation is the most common known inherited genetic cause of mental retardation and of autism.

Answer 43

fragile X syndrome

Question 44

Males with the so-called premutation (50 to 200 CGG repeats) are at risk for

Answer 44

fragile X-associated tremor/ataxia syndrome (FXTAS).

Question 45

Mutations in genes that encode LH and FSH receptors also have been reported. These defects prevent normal responses to circulating gonadotropins, a condition termed

Answer 45

resistant ovary syndrome

Question 46

Syndrome which is characterized by sensorineural hearing loss and ovarian dysfunction Ovarian disturbances range from gonadal dysgenesis and primary amenorrhea to POI. Associated neurologic features include learning disabilities, developmental delay, and cerebellar ataxia

Answer 46

Perrault syndrome

Question 47

How to minimize the effect of chemotherapy on ovaries and decrease the incidence of POI?

Answer 47

chemotherapeutic drugs, alkylating agents are believed to be particularly damaging to ovarian function. Preventive adjuvant GnRH analogues may lower rates of chemotherapy-induced POI (Chap. 27, p. 594). Although this approach remains controversial, recent studies and metanalyses show promising results (Chen, 2011; Lambertini, 2018).

Question 48

the most frequent cause of acquired pituitary dysfunction

Answer 48

Pituitary adenomas

Question 49

Beside sheehan syndrome what other peripartum condition can be associated with amenorrhea ?

Answer 49

a rare condition, peripartum lymphocytic hypophysitis can be a dangerous cause of pituitary failure.

Question 50

When isolated, neural-tube defect inheritance is multifactorial, and the recurrence risk without periconceptional folic acid supplementation is – to – percent

Answer 50

When isolated, neural-tube defect inheritance is multifactorial, and the recurrence risk without periconceptional folic acid supplementation is 3 to 5 percent

Question 51

PCOS accounts for – to – percent of cases of hirsutism, which typically begins in late adolescence or the early 20s. Idiopathic hirsutism is the —— most frequent cause

Answer 51

PCOS accounts for 70 to 80 percent of cases of hirsutism, which typically begins in late adolescence or the early 20s. Idiopathic hirsutism is the second most frequent cause

Question 52

Summary of PCOS testing

Answer 52

Serum levels of FSH, LH, TSH, Total T, free T, estradiol, PRL, 17-OH-P, DHEAS, 2-hr GTT, HbA1 c, lipid profile Measurement of BMI, waist circumference, BP.

Question 53

Important notes Regarding PCOM

Answer 53

polycystic appearance of the ovaries can often be found in other conditions of androgen excess, such as CAH, Cushing syndrome, and exogenous use of androgenic medications. For this reason, PCOM found during sonographic examination is not used solely for PCOS diagnosis. Importantly, PCOM often reflects normal adolescent ovarian physiology (Hickey, 201 I; Kristensen, 2010). Thus, sonography for PCOS evaluation is not recommended within 8 years of menarche.

Question 54

In patients with amenorrhea PCOS who are not candidates for combination hormonal contraception, progesterone withdrawal is recommended every 1 to 3 months. Examples of regimens used include:

Answer 54

medroxyprogesterone acetate (MPA), 5 to 10 mg orally daily day for 12 days, or micronized progesterone, 200 mg orally each evening for 12 days.

Question 55

Mode of inheritance of Androgen insensitivity syndrome

Answer 55

X-linked recessive

Question 56

Primary ovarian insufficiency is diagnosed by

Answer 56

Primary ovarian insufficiency is diagnosed in women younger than 40 years who have had at least 4 months of amenorrhea and two menopausal FSH concentrations obtained at least 1 month apart.

Question 57

There are three main enzyme defects that can lead to CAH disorder:

Answer 57

1) 21-hydroxylase deficiency ( most common)
2) 11-C-hydroxylase deficiency,(associated with hypertension in more than two thirds of patients and with hypokalemia)
3) 33-hydroxysteroid dehydrogenase deficiency.

Question 58

21-hydroxylase deficiency CAH where is the mutation and mode of inheritance

Answer 58

caused by a monogenic, autosomal recessive mutation on chromosome 6 involving CYP21A2

Question 59

Asherman syndrome occurs most commonly because of endometrial trauma or infe ction, particularly after pregnancy when estradiol levels nadir. The syndrome occurs in up to – - –% of patients treated with a D&C in the postpartum period.

Answer 59

Asherman syndrome occurs most commonly because of endometrial trauma or infe ction, particularly after pregnancy when estradiol levels nadir. The syndrome occurs in up to 20-25% of patients treated with a D&C in the postpartum period.

Question 60

The Endocrine Society recommends screening all women with PCOS every – – – years for diabetes and impaired glucose tolerance using the 2-hour oral glucose tolerance test.

Answer 60

The Endocrine Society recommends screening all women with PCOS every 3–5 years for diabetes and impaired glucose tolerance using the 2-hour oral glucose tolerance test.

Question 61

Women with PCOS have a —- fold to —fold increased risk of developing type 2 diabetes compared with women who do not have PCOS

Answer 61

Women with PCOS have a fivefold to 10-fold increased risk of developing type 2 diabetes compared with women who do not have PCOS

Question 62

Patient with PCO, acne and Hirsutism, most appropriate OCP?

Answer 62

Ethinylestradiol+cyproterone acetate