Amenorrhea Flashcards
Cryptomenorrhea
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.
Primary amenorrhea
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.
The incidence of primary amenorrhea is
less than 0.1%.
Curettage for a missed abortion results in a high incidence of IUA formation (30%).
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.
Central Nervous System Structural Abnormalities causes of amenorrhea
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.
Drugs causes amenorrhea
Drugs
Phenothiazine derivatives, certain antihypertensive agents,
Type 2 DM is more prevalent (—to —- times higher) in women with PCOS of reproductive age
Type 2 DM is more prevalent (3 to 5 times higher) in women with PCOS of reproductive age.
Treatment of PCOS
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
Amenorrhea can be classified by Functional Compartments The reproductive axis can be divided into the functional compartments:
1-Outflow: uterus, cervix and vagina
2- Gonadal: ovaries
3-anterior pituitary gland
4- hypothalamus
There are three types of Functional hypothalamic amenorrhea (FHA)
weight loss-related, stress-related, and exercise-related amenorrhea.
leuprolide stimulation test,
may be used to evaluate abnormal pubertal development
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.
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.
Ddx of PCOS
- 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
Obstetrical complications of women with PCOS
Increased risk GDM
Preeclampsia
Caesarean section
Preterm/postterm delivery
Secondary Amenorrhea defined as
3 months Without Cycle if regular
Or 6 months if irregular
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.
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.
Perrault syndrome
(46,XX; gonadal dysgenesis and sensorineural deafness)
Swyer syndrome karyotype and pathogenesis
(46,XY; gonadal dysgenesis)
Diagnosis of Cushing Syndrome
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
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.
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%.
Cushing disease Vs. Cushing syndrome
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.
17-hydroxyprogesterone level is used as a screening test for
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.
the best screening test to confirm the diagnosis of cushing syndrome is
overnight dexamethasone suppression test.
Laboratory findings suggestive of an ovarian androgen-producing tumor include
a total testosterone level greater than 200 ng/dL and a reversal in the androstenedione-to-testosterone ratio.
Androgen insensitivity syndrome (AIS) also referred to as Reifenstein syndrome.
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).
The causes of primary ovarian insufficiency include
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.
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
Fragile X syndrome
Women with infertility due to primary ovarian insufficiency who have a normal karyotype should be tested for the fragile X premutation.
Women who have not resumed menstrual function within 6 months of stopping OC use should be evaluated for secondary amenorrhea.
Waiting more than 6 months before initiation of a formal evaluation would delay diagnosis and treatment of her amenorrhea.
The criterion standard for confirming the diagnosis of nonclassic CAH is
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.
The two most common causes of gestational hyperandrogenism
1) luteomas of pregnancy and 2) hyperreactio luteinalis.
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 ?
Hyperreactio luteinalis
When Biopsy of the endometrium should be considered in pcos patients
older than 35 years with unopposed estrogen production and amenorrhea that exceeds 12 months.
with PCOS have an approximately ?-fold increased risk of endometrial cancer,
with PCOS have an approximately 2.7-fold increased risk of endometrial cancer,
Amenorrhea Evaluation is considered for an adolescent:
(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).
Secondary amenorrhea Definition
amenorrhea for 3 months or fewer than nine cycles per year to be investigated (American Society for Reproductive Medicine, 2008; Klein, 2013).
POI is defined as
loss of oocytes and the surrounding support cells prior to age 40 years.
The diagnosis of POI is determined by
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).
the most frequent cause of POI is
Gonadal dysgenesis
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.
(Swyer syndrome)
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
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.
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.
fragile X syndrome
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.
fragile X syndrome
this fully expanded mutation is the most common known inherited genetic cause of mental retardation and of autism.
fragile X syndrome
Males with the so-called premutation (50 to 200 CGG repeats) are at risk for
fragile X-associated tremor/ataxia syndrome (FXTAS).
Mutations in genes that encode LH and FSH receptors also have been reported. These defects prevent normal responses to circulating gonadotropins, a condition termed
resistant ovary syndrome
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
Perrault syndrome
How to minimize the effect of chemotherapy on ovaries and decrease the incidence of POI?
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).
the most frequent cause of acquired pituitary dysfunction
Pituitary adenomas
Beside sheehan syndrome what other peripartum condition can be associated with amenorrhea ?
a rare condition, peripartum lymphocytic hypophysitis can be a dangerous cause of pituitary failure.
When isolated, neural-tube defect inheritance is multifactorial, and the recurrence risk without periconceptional folic acid supplementation is – to – percent
When isolated, neural-tube defect inheritance is multifactorial, and the recurrence risk without periconceptional folic acid supplementation is 3 to 5 percent
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
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
Summary of PCOS testing
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.
Important notes Regarding PCOM
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.
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:
medroxyprogesterone acetate (MPA), 5 to 10 mg orally daily day for 12 days, or micronized progesterone, 200 mg orally each evening for 12 days.
Mode of inheritance of Androgen insensitivity syndrome
X-linked recessive
Primary ovarian insufficiency is diagnosed by
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.
There are three main enzyme defects that can lead to CAH disorder:
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.
21-hydroxylase deficiency CAH where is the mutation and mode of inheritance
caused by a monogenic, autosomal recessive mutation on chromosome 6 involving CYP21A2
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.
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.
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.
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.
Women with PCOS have a —- fold to —fold increased risk of developing type 2 diabetes compared with women who do not have PCOS
Women with PCOS have a fivefold to 10-fold increased risk of developing type 2 diabetes compared with women who do not have PCOS
Patient with PCO, acne and Hirsutism, most appropriate OCP?
Ethinylestradiol+cyproterone acetate
