Secondary amenorrhea Flashcards
Definition of secondary amenorrhea
Cessation of menses for at least 6 months in a pre-menopausal woman who has been menstruating
Causes of secondary amenorrhea
!!! TRO PREGNANCY (esp ECTOPICS)
Hypothalamus
- Systemic stresses (excessive exercise, significant weight loss (anorexia/bulimia), emotional stress, chronic illness)
- Kallman’s syndrome
- Neoplasms
Pituitary
- Prolactinoma
- Hyperprolactinemia secondary to pituitary adenoma, stress, antipsychotic drugs, primary hypothyroidism, breast feeding, PCOS (Prolactin suppresses FSH and LH**)
Ovary
A. Ovarian failure (hypergonadotropic hypognonadism)
- Surgical removal of ovaries
- Chemo or radiotherapy
- Turner’s syndrome (if manifests later)
- Autoimmune
B. Ovarian dysfunction (normogonadotropic)
- PCOS [*most common]
- Late onset congenital adrenal hyperplasia
- Hyperandrogenism (androgen secreting tumour, drugs)
- Adrenal disorders (adrenal secreting tumour, Cushing’s syndrome)
Common cause of hypothalamus: hypogonadotropic hypogonadism
Systemic stresses
- Excessive exercise
- Significant weight loss (anorexia/bulimia)
- Emotional stress
- Chronic illness
Causes of hyperprolactinemia
- Pituitary adenoma
- Stress
- Antipsychotic drugs
- Primary hypothyroidism
- Breast feeding
- PCOS
Causes of low serum prolactin level
Sheehan’s: Massive postpartum haemorrhage reduces blood flow to the pituitary gland
Head trauma
Destructive neoplastic process
Classify causes of secondary amenorrhea by hormone levels
Hypogonadotropic hypogonadism: low FSH, low FH, low estradiol
- Hypothalamus
- Pituitary
Hypergonadotropic hypogonadism: high FSH, high LH, low estradiol
- Ovarian failure
Normogonadotropic normogonadism: normal FSH, normal LH, normal estradiol, INCREASED testosterone
- Ovarian dysfunction
What is premature ovarian failure?
Ovarian failure (ovaries stop working) before 40 years old
- lack of oestrogen stimulation results in high FSH*, LH due to negative feedback to pituitary (hypergonadotropic hypogonadism)
Triad of PCOS
Rotterdam criteria
1. Oligomenorrhoea &/or anovulation
- Fewer than 8 menstrual cycles/year
2. Hyperandrogenism
- Clinical: Virilisation/ Hirsutism/ Acne/ Male Balding Pattern (Ferriman-Gallwey score)
OR
- Biochemical: High serum testosterone
3. Polycystic ovarian morphology
- Transvaginal ultrasound:
≥12 peripheral follicles (2-9mm in diameter) &/or
Ovarian Volume > 10cm3
(even if only one ovary fits this definition is sufficient)
ANY 2/3 criterial fulfilled
+ EXCLUSION of late onset congenital adrenal hyperplasia, hyperandrogenism (androgen secreting tumour, drugs), adrenal disorders (adrenal secreting tumour, Cushing’s syndrome)
What is PCOS?
Ovaries that are enlarged by multiple small follicles that do not develop into dominant follicles but are arrested at antral follicle stage
- Common around puberty
Risk factors of PCOS
Obesity/ Metabolic syndrome
T1/2 DM
1st degree relatives with PCOS
Women with anovulatory infertility
Clinical presentation of PCOS
Gynae consequences
1. Menstrual irregularity
- Oligomenorrhea –> Lining of the endometrial wall has overgrown and cause heavy bleeding once it actually bleeds
- Secondary amenorrhea
2. Anovulatory subfertility/ recurrent miscarriages
Hyperandrogenism:
- Hirsutism* with male pubic hair distribution
- Acne
- Deepening of voice
- Decreased breast tissue
- Male balding pattern
Metabolic syndrome
- obesity, DM, HTN, HLD
Complications of PCOS
- Metabolic syndrome
- Endometrial hyperplasia due to chronic anovulation leading to unopposed estrogen (Endometrial CA)
- Infertility
- Increased CVS risk
Management PRINCIPLES of PCOS
- Amelioration of hyperandrogenic features (hirsutism, acne, scalp hair loss)
- Manage underlying metabolic abnormalities and reduction of risk factors for type 2 diabetes and cardiovascular disease
- Prevention of endometrial hyperplasia and carcinoma, which may occur as a result of chronic anovulation
- Contraception for those not pursuing pregnancy, as women with oligomenorrhea ovulate intermittently and unwanted pregnancy may occur
- Ovulation induction for those pursuing pregnancy
If patient does NOT desire fertility, the following management can be administered
Conservative:
- Lifestyle Change (Diet/ Exercise/ Weight loss target >5%, significantly improves fertility)
Interventional:
1. HORMONAL THERAPY
Combined estrogen-progestin oral contraceptives
- Reduce hyperandrogenism, reduce hirsutism
- Reduce menstrual dysfunction: Daily exposure to progestin antagonizes the endometrial proliferative effect of estrogen
- NO menses
OR
Cyclic progestin therapy
- Induces regular withdrawal uterine bleeding and reduce the risk of endometrial hyperplasia
- For patients who have irregular menses <once/3 months
- Patient will have regular menses
OR
Continuous progestin therapy
- For patients with very heavy menses, anemia
- Patient will not have menses while taking continuous progestin
OR
Mirena
- Metformin
- Antiandrogen therapy
- Spironolactone
- Finasteride (inhibits 5-alpha-reductase type 2, which converts testosterone to DHT), Dutasteride
- Cyproterone acetate
If patient DESIRES fertility, the following management can be administered
Conservative:
- Lifestyle Change (Diet/ Exercise/ Weight loss target >5%, significantly improves fertility)
Interventional:
1. OVULATION INDUCTION
- Letrozole (preferred)
- Clomiphene citrate
Blocks negative feedback (estrogen receptors in hypothalamus) thus provoking GnRH release -> LH/FSH release -> Ovulation
- Metformin
- Exogenous gonadotropins (FSH injections)
- Surgical ovarian resection and drilling
- Burns ovarian tissue/ stroma, reduces androgens (produced by ovarian stroma)
- Indicated if clomiphene fails - In-vitro fertilisation
Side effect of ovulation induction
High risk of ovarian hyperstimulation syndrome
Multiple pregnancies (10% chance)
Side effect of surgical ovarian resection and drilling
Tubal adhesions
Premature ovarian failure
Management of hyperprolactinemia
If desire fertility vs no fertility
Fertility: Bromocriptine
No fertility: Bromocriptine or cabergoline
Management for premature ovarian failure
Hormonal therapy (E+P)
IVF
Drugs that can cause hyperprolactinemia
Anti-emetics/ Antipsychotics/ Antidepressants
Investigations for PCOS
Amenorrhea panel with typical findings in PCOS being
- normal FSH ± ↑LH
- reversed LH: FSH ratio (~3:1)
- normal/slightly elevated estradiol
- elevated testosterone
- elevated prolactin
Imaging
Ultrasound pelvis
CT abdomen for androgen secreting
tumor of the adrenals
Screening for comorbidities
- HbA1c, lipid panel, BP
TRO Others
- serum dihydroepiandrosterone-sulphate: elevated in adrenal hyperandrogenic disorders
- serum 17-hydroxyprogesterone: elevated in late onset CAH
- Cushing’s: 24h urinary free cortisol & low dose dexamethasone suppression test
Why does PCOS lead to anovulation?
Hormonal changes in PCOS
-> Increased serum LH levels increases amount of ovarian androgen secretion
-> High androgen levels induce atresia of ovarian follicles, preventing normal follicular development leading up to ovulation
-> High androgen levels increase peripheral aromatization of androgens into oestrogen, resulting in elevated oestrogen levels which suppress FSH secretion
-> Lack of normal estrogen rise results in lack of LH surge, with resultant anovulation
Investigations for secondary amenorrhea
Urine pregnancy test!
Bloods
2. Amenorrhea panel:
FSH, LH, Prolactin, TSH
Estradiol, Testosterone
- very high testosterone > 5nmol/L is suggestive of an androgen producing tumor
3. Pituitary hormones: TSH, GH, ACTH, PRL (for hypothal-pit)
- high prolactin > 1000 is suggestive of a pituitary adenoma
Imaging
4. Pelvic U/S
- ovarian tumors, PCOS
- detect structural abnormalities of the reproductive tract & presence of gonads
5. MRI brain/pituitary gland if serum prolactin levels > 1000mlU/L (for hypothal-pit)
6. CT abdomen: adrenal tumors
Others
- serum dihydroepiandrosterone-sulphate: elevated in adrenal hyperandrogenic disorders
- serum 17-hydroxyprogesterone: elevated in late onset CAH
- Cushing’s: 24h urinary free cortisol & low dose dexamethasone suppression test
- ??cyclical estrogen/progesterone test: tests for a withdrawal bleed
Complications of premature ovarian insufficiency
Infertility
CVS disease
Osteoporosis
Important lab investigation for POI
FSH
Causes of premature ovarian insufficiency
Genetic - Turner’s
Autoimmune - Addison’s, thyroid disorders
Iatrogenic - Chemotherapy, radiotherapy
