Amenorrhea Flashcards
Amenorrhea
Primary vs secondary
Primary Amenorrhea -
No menses by age 13 without evidence of secondary sex characteristics
Lack of breast development, lack of pubic/axillary hair growth
No menses by age 15 with secondary sex characteristics
Secondary Amenorrhea -
No menses for 3 cycles or 3-6 months
Prevalence in US: Primary <0.1% vs Secondary 4%
Amenorrhea
causes
Most common - genetic disorders/gonadal dysgenesis (43%)
Pregnancy (trauma/abuse)
Hypogonadotropic hypogonadism *
Hypergonadotropic hypogonadism
Ovarian failure/ovarian insufficiency *
PCOS *
Anatomical defects
Müllerian anomaly (15%), transverse vagina or imperforate hymen
* = more likely cause secondary amenorrhea
Amenorrhea
Hypogonadotropic Hypogonadism
↓estradiol/FSH
“brain” (hypothalamus or pituitary)
Normal Karyotype (46, XX)
Constitutional Delay
Associated with stress, eating disorders, extreme exercise
Medications (antipsychotics), opioid drug abuse
Pituitary tumors
Kallmann syndrome - congenital GnRH deficiency
(anosmia - lack of sense of smell)
Endocrine disorders
Hyperprolactinemia
Hypothyroidism
Cushing Syndrome
Amenorrhea
Hypergonadotropic Hypogonadism
↑FSH/LH
Low estradiol ( = no biofeedback)
“Ovaries”
Gonadal agenesis/dysgenesis
45 XO Turner’s syndrome
Müllerian vs 46XY androgen insufficiency
Fragile X premutation
Chemotherapy/Radiation
Autoimmune oophoritis
Infection - Mumps
Surgery
Turner’s Syndrome
general
45 XO, mosaic 45X or 46XX (streak ovaries)
Short stature, webbed neck, shield chest with wide spaced nipples
Cardiac defects (bicuspid AV, coarctation aorta), aortic aneurysms
Horseshoe kidney
Increased incidence DM, autoimmune disorders, hypothyroidism
Growth hormone ages 2-5
HRT ages 12-50
Needs cardiology referral -due to possible heart defects
Referral to pediatric endocrine for GH
Primary Amenorrhea
labs
Labs/Tests:
HCG
TSH
Prolactin
FSH/LH
Free/total testosterone
PUS
Karotype
primary amenorrhea
Hypogonadotropic Hypogonadism – treatment
Correcting underlying pathology, if possible
Lifestyle Changes
Therapy
Provide estrogen/progesterone
Breast development
Closes epiphyses
Maintains bone density
Increases uterine size/proper endometrium
Ovulation Induction:
Exogenous FSH/LH
Monitor for weight - low birth weight, preterm birth
primary amenorrhea
Hypergonadotropic Hypogonadism - treatment
Provide estrogen/progesterone
Breast development
Maintains bone density
Increases uterine size/endometrium
If Y chromosome - needs gonadal removal
Germ cell tumors
Fertility - Egg donation, Adoption
Secondary Amenorrhea
causes
Most common cause - pregnancy
Anovulation
PCOS
Hypothyroidism
Hyperprolactinemia
physiologic = breastfeeding
Medications (OCP)
Estrogen Deficiency
Perimenopause
Premature Ovarian Failure (< 40 y/o) – aka primary ovarian insuffiency (POI)
Hypothalamic/Pituitary Insufficiency
Sheehan’s Syndrome
Tract Obstruction
Cervical stenosis - s/p conization
Asherman Syndrome - intrauterine adhesions s/p D&C
Hypogonadotropic Hypogonadism
Stress
Extreme exercise
Eating disorders
Polycystic Ovarian Syndrome
general and RF
Multisystem disorder that is based in androgen excess, ovulatory dysfunction and/or polycystic ovaries
Most common endocrine/metabolic disorder in females; 10-15%
Risk factors –
Genetics – first degree relative with PCOS – estimated about 70%
Premature menarche
Obesity? and/or insulin resistance (regretless of body weight)
Use of antiseizure medications – valproic acid
PCOS
Genetics
Genetics + Environment both play a role
Genome-wide association studies have determined certain susceptibility genes: loci at 2p16.3, 2p21, and 9q33.3, and involving the LH /human chorionic gonadotropin (HCG) receptor, a thyroid adenoma locus, DENND1A
PCOS
Patho
↑GnRH pulse frequency = ↑LH (>LH:FSH)
Hypersecretion of LH →↑androgen production by the ovarian theca cells
This impairs follicular development
There is also thought to be ovarian resistance to FSH due to high levels of AMH
Ovulation is inhibited and progesterone DOES NOT ELEVATE due to no corpus luteum formation
“vicious cycle”
Insulin reacts with thecal cells = ↑testosterone
Create negative feedback to hypothalamus/pituitary
Decrease insulin sensitivity which then leads to the pancreas releasing more insulin
More circulating insulin = more insulin to react with thecal cells to ↑testosterone
PCOS
Rotterdam criteria
2 out of the 3
Anovulation or oligo-ovulation
Hyperandrogenism – elevated free testosterone or clinical signs of this
Polycystic ovaries seen on PUS – “string of pearls”
PCOS
Signs of hyperandrogenism
Hirsutism
Excess in terminal hair (thick, pigmented) body hair
Male distribution: upper lip, chin, periareolar, midsternum, lower abdomen
Acne vulgaris – normally along jaw line
Polycystic Ovaries
US
Seen on PUS (usually both transabdominal and TVUS)
Presence of 12 or more follicles (small 2-9mm) or increased ovarian volume >10ml
“string of pearls”
PCOS
Labs/imaging
Testing for hyperandrogenism: total and free testosterone
Ruling out other causes of oligomenorrhea:
TSH
Prolactin
HCG
17-hydroxyprogesterone – r/o non classical congenital adrenal hyperplasia (NCCAH)
PUS – transabdominal and TVUS
PCOS
Tx
not desiring pregnancy/ post children/>35
Not desiring pregnancy:
Control bleeding with OCPs – usually either drospirenone or norgestimate progestin (most testosterone suppressing)
Yaz, Yasmin, Slynd; Ortho Cyclen, Ortho Tri Cyclen
Progesterone IUD – this will not help acne or hirsutism
Control hirsutism and acne by reducing testosterone
Metformin 850-1000mg BID
Spironolactone 100mg q day
Post childbearing/>35y/o
Same as ←: control bleeding and hirsutism
Manage uterine protection through perimenopause either with OCP, progestin IUD, cyclic progesterone
PCOS
Tx for those desiring pregnancy
Desiring pregnancy:
Metformin 850-1000mg BID
Weight management – 5-10% can significantly reduce serum androgen levels
Letrozole (Femara) 5-7.5mg Days 3-7
now considered first line
Clomiphene citrate (Clomid)
Gonadotropin therapy – injectables; cost and multiples are a concern
Secondary Amenorrhea
Sheehan’s Syndrome - s/p postpartum hemorrhage
Anterior pituitary becomes hypoxic during PPH then necrosis occurs
Results in difficulty of breastfeeding or absence of lactation
Loss of axillary/pubic hair
Acute symptoms: hypotension, tachycardia (hypovolemia) with hyponatremia and persistent hypoglycemia
Similar symptoms to hypothyroidism - fatigue, hypotension, wt gain, constipation
Hormones affected in order of severity - GH, prolactin/FSH/LH/ACTH and last TSH
MRI of pituitary to confirm diagnosis - empty sella 70%
Sheehan’s syndrome- Secondary Amenorrhea
Tx
Treat hypothyroidism - levothyroxine
Cortisol deficiency - prednisone
Gonadotropin deficiency - HRT and growth hormone
Rarely, diabetes insipidus - desmopressin (DDAVP)
Referral to endocrine!
Secondary Amenorrhea
Labs
Labs: HCG, prolactin, FSH/estradiol, TSH, free/total testosterone
PUS
If labs are normal, progesterone challenge
Prometrium 200mg nightly x 7-10 days, withdrawal with in 2 weeks (Provera 10mg as well)
Bleeding = estrogen present, lack of progesterone (PCOS)
No bleeding = low estrogen levels (Hypo/hypo), premature ovarian failure or outflow tract (Asherman’s or cervical stenosis)
Then give estrogen/progesterone together -
Bleeding = hypo/hypo or POF
No bleeding = outflow tract
Outflow tract -
Hysteroscope/HSG
