21: Amenorrhea Flashcards
Primary amenorrhea
absence of menarche by age 16 or 4 years after thelarche.
Primary amenorrhea can be caused
(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.
The workup of primary amenorrhea is usually organized into four categories based on?
presence or absence of a uterus and the presence or absence of breast development.
absence of both uterus and breasts, karyotype usually reveals ?
tests?
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
In the absence of a uterus and presence of breasts, ? will differentiate between
karyotype will ddx btw Müllerian agenesis/MRKH (XX) and testicular feminization/enzyme deficiency in testosterone synthesis (XY)
In the absence of breasts and presence of a uterus ? will ddx btw ?
FSH will differentiate between hypergonadotropic (^FSH) and hypogonadotropic (low FSH) hypogonadism. Karyotype may be necessary to rule out gonadal agenesis in a 46,XY.
Patients with both a uterus and breasts should be evaluated as if presenting with ?
secondary amenorrhea.
-other etiologies: disruption of H-P axis, congenital abnormalities of the genital tract
Anatomic abnormalities including ? may lead to secondary amenorrhea. These patients fail to respond to ?
Asherman syndrome and cervical stenosis
estrogen and progesterone withdrawal
high levels of ? is a common cause of secondary amenorrhea
prolaction (hyperprolactinemia)
Patients with normal prolactin levels may be given a ? to investigate ?
progesterone challenge
adequacy of endogenous estrogen production and the outflow tract
With progesterone challenge failure, the differential diagnosis becomes ? that can be differentiated by an ?.
hypergonadotropic or hypogonadotropic hypogonadism
FSH measurement
tx of amenorrheic pts who are not seeking fertility vs those who are seeking fertility
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.
Secondary amenorrhea
causes?
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
Testicular feminization, aka androgen insensitivity syndrome (AIS), results from ?
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
Primary ovarian failure results in low levels of ? but elevated levels of ? termed ?
low estradiol
high gonadotropins
hypergonadotropic hypogonadism
Savage syndrome
failure of the ovaries to respond to FSH and LH secondary to a receptor defect
Turner syndrome
(45,XO), the ovaries undergo such rapid atresia that by puberty there are usually no primordial oocytes
Defects in the enzymes involved in steroid biosynthesis, particularly ?, can result in ?
17-hydroxylase
amenorrhea and absence of breast development given the lack of estradiol.
Swyer syndrome
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
Kallmann syndrome
hypogonadotropic hypogonadism, congenital absence of GnRH and is commonly associated with anosmia
Other ways that GnRH transport may be disrupted
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.
here may be defects in GnRH pulsatility in cases of ?
anorexia nervosa, extreme stress, athletics, hyperprolactinemia, hypothyroidism, rapid or severe weight loss, and constitutionally delayed puberty.
treatment of hypergonadotropic vs hypogonadotropic hypogonadism
hyper: often have irreversible ovarian failure and will require ERT
hypo: require further workup as patients with secondary amenorrhea
Asherman syndrome
etiologies?
presence of intrauterine synechiae or adhesions, usually secondary to intrauterine surgery or infection.
-D/C, myomectomy, C section, endometritis
ovarian failure may be due to ?
how to treat ?
- 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
Polycystic ovary syndrome (PCOS), aka ?
diagnosed with 2/3 of the following:
Stein-Leventhal syndrome
oligo or anovulation, clinical or laboratory evidence of hyperandrogenism (hirsutism, male balding, acne), and polycystic ovaries on US
in the case of PCOS, chronic anovulation leads to elevated levels of ? which leads to ?
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
In PCOS patients desiring pregnancy, ovulation induction may be performed using ?
ovulation can be significantly increased by ?
clomiphene citrate (Clomid) (acts as an antiestrogen to stimulate gonadotropin release) weight loss
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
metformin
For patients who are not currently interested in fertility, the goal of therapy is ? with ?
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
PCOS pts have increased risk of
HTN, OSA, CAD, T2DM, insulin resistance
Prolactin release is inhibited by ? and stimulated by ?
dopamine
serotonin and thyrotropin-releasing hormone (TRH)
etiologies of hyperprolactinemia
prolactinoma, hypothyroidism, idiopathic,
Drug-induced, Interruption of H-P relationship, Pituitary stalk section, Peripheral neural stimulation, Nipple stimulation, Spinal cord lesion, CNS disease
drugs that can induce hyperprolactinemia
dopamine antagonists (Haldol, Reglan, phenothiazine), TCAs, estrogen, monoamine oxidase (MAO) inhibitors, and opiates
secondary amenorrhea work up
B-hCG, H/P focused on s/s of hypothyroidism, hyperprolactinemia, hyperandrogenism, get TSH, prolactin levels
if PRL elevated check
med list, visual fields, CNs, breast exam, MRI to r/o H-P lesion
if progesterone challenge positive (+ w.drawal bleeding), amenorrhea is usually secondary to ?
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
if progesterone challenge negative, must evaluate with ?
if still no bleeding, suspect ?
if bleeding suspect ? next step?
- 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
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 ?
human menopausal gonadotropin (hMG) or recombinant GnRH
ovarian hyperstimulation
