Differentials
Common
Eating disorders or female athlete triad
History
weight loss, anorexia, altered bowel habits, sleep disturbances, dry skin, competitive sports
Exam
low BMI (10% less than ideal body weight), normal secondary sexual characteristics, normal external and internal genitalia
1st investigation
Emotional or physical stress
History
weight loss, anorexia, sleep disturbances, dry skin, prescription drugs
Exam
low BMI (10% less than ideal body weight), normal secondary sexual characteristics, normal external and internal genitalia
1st investigation
Post-contraception with depot medroxyprogesterone
History
history of depot medroxyprogesterone
Exam
normal secondary sexual characteristics, normal external and internal genitalia
1st investigation
Hyperprolactinaemia
History
galactorrhoea (some patients), headache or visual disturbances (prolactinoma); may present with oligomenorrhoea if prolactin levels are not extremely elevated
Exam
visual field deficit (some patients)
1st investigation
- serum human chorionic gonadotropin:
negative
- serum prolactin:
elevated; >100 nanograms/mL or 100 micrograms/L is highly suggestive of prolactinoma
More - serum follicle-stimulating hormone (FSH):
low to normal
More - serum oestradiol:
low
More - serum thyroid-stimulating hormone:
usually normal
More - MRI brain:
possible pituitary tumour
- pelvic ultrasound:
thin to variable endometrial echo-complex
More
Polycystic ovary syndrome (PCOS)
History
slowly progressive symptoms, deepening of voice, male-pattern hair growth or loss, oily skin, weight gain, oligoanovulatory cycles to amenorrhoea (if peripubertal onset, may present with delayed menarche), history of premature pubarche, depression
Exam
androgenic alopecia, acanthosis nigricans, increased waist-hip ratio, clitoromegaly, acne, hirsutism, obesity (BMI >30)
1st investigation
- serum human chorionic gonadotropin:
negative
- serum follicle-stimulating hormone (FSH):
normal
More - serum oestradiol:
normal to elevated
More - serum thyroid-stimulating hormone:
normal
- serum prolactin:
normal
- serum dehydroepiandrosterone sulphate:
elevated
- total serum testosterone:
elevated; marked elevation suggests ovarian/adrenal tumour
More - free serum testosterone:
elevated
More - serum 17-hydroxyprogesterone (17-OHP):
normal fasting levels help rule out 21-hydroxylase deficiency
More - 2-hour oral glucose challenge:
elevated insulin levels
More - fasting serum lipid profile:
elevated triglycerides and LDL
More - pelvic ultrasound:
polycystic ovaries; variable endometrial echo-complex
Idiopathic premature ovarian failure
History
age <40 years, vasomotor symptoms, vaginal dryness, decreased libido, fatigue, weight gain
Exam
post-pubertal external genitalia, adult secondary sexual characteristics
1st investigation
Post-chemoradiation ovarian failure
History
vasomotor symptoms, vaginal dryness, decreased libido, fatigue, weight gain
Exam
normal adult secondary sexual characteristics
1st investigation
Other investigations
- serum LH:
elevated
More - progestogen challenge test:
no withdrawal bleed
Chromosomal abnormality (Fragile X carrier, Turner's syndrome mosaic)
History
age <40 years, vasomotor symptoms, vaginal dryness, decreased libido, fatigue, weight gain; may lack hypo-oestrogenic complaints but stop cycling
Exam
Turner's mosaic: fewer physical manifestations as compared with full syndrome; may have isolated oligoamenorrhoea; Fragile X carrier: may have large ears
1st investigation
Non-classic congenital adrenal hyperplasia
History
presents in late childhood to early adult life; obesity, hirsutism, acne, weight gain, history of premature pubarche
Exam
androgenic alopecia
1st investigation
- serum human chorionic gonadotropin:
negative
- serum follicle-stimulating hormone (FSH):
normal
More - serum oestradiol:
normal to elevated
More - serum thyroid-stimulating hormone:
normal
- serum prolactin:
normal
- serum dehydroepiandrosterone sulphate:
elevated
- total serum testosterone:
elevated; marked elevations suggests ovarian/adrenal tumour
More - serum 17-hydroxyprogesterone (17-OHP):
elevated fasting levels (>6 nanomol/L or >200 nanograms/dL)
More - pelvic ultrasound:
variable endometrial echo-complex
Hypothyroidism
History
oligomenorrhoea more common than amenorrhoea; lethargy, dry skin, constipation, weight gain, paraesthesias, cold intolerance, galactorrhoea
Exam
low resting heart rate, peri-orbital puffiness, delayed ankle deep tendon reflexes, cold and coarse skin
1st investigation
Uncommon
Malnutrition or chronic disease state
History
history of chronic disorder (e.g., coeliac disease), weight loss, anorexia
Exam
low BMI (10% less than ideal body weight), normal secondary sexual characteristics, normal external and internal genitalia
1st investigation
Empty sella syndrome
History
mass in sella turcica or previous central nervous system surgery/radiation/infarction; headache, galactorrhoea, or visual disturbances may be seen with associated prolactinoma
Exam
visual field deficit (some patients)
1st investigation
- serum human chorionic gonadotropin:
negative
- serum follicle-stimulating hormone (FSH):
low to normal
More - serum oestradiol:
low
More - serum thyroid-stimulating hormone:
low to normal
- serum prolactin:
normal; >100 nanograms/mL (or 100 micrograms/L) highly suggestive of prolactinoma
- MRI brain:
pituitary lesion or empty sella
- pelvic ultrasound:
thin to variable endometrial echo-complex
More
Sheehan's syndrome (postpartum pituitary necrosis)
History
severe obstetric haemorrhage, hypotension, and shock with postpartum panhypopituitarism (after volume and blood resuscitation), nausea, vomiting, lethargy, failure to breast-feed, slowed mental function, fatigue, weight loss, delayed symptoms of hypothyroidism
Exam
postural hypotension, loss of axillary and pubic hair, adrenal crisis (with skin de-pigmentation), rapidly involuting breasts, peri-orbital oedema
1st investigation
- serum human chorionic gonadotropin:
negative
- serum follicle-stimulating hormone (FSH):
low
More - serum oestradiol:
low
More - serum thyroid-stimulating hormone:
low
More - serum free thyroxine (T4):
low
More - serum prolactin:
normal
- serum growth hormone:
low
- serum adrenocorticotropic hormone:
low to normal
More - serum sodium:
may be low
More - morning serum cortisol:
may be low
More - MRI brain:
sella empty or cerebrospinal fluid-filled; potentially small pituitary gland
More - pelvic ultrasound:
thin to variable endometrial echo-complex
More
Post-encephalitis
History
previous infectious process, headache, altered vision
Exam
visual field defects, normal phenotypic female
1st investigation
Androgen-producing ovarian tumour
History
rapidly progressive symptoms, obesity, hirsutism, acne, deepening voice, male-pattern hair growth or loss, oily skin, weight gain, oligoanovulatory cycles to amenorrhoea
Exam
androgenic alopecia, clitoromegaly, male-pattern hair growth, increased muscle mass
1st investigation
- serum human chorionic gonadotropin:
negative
- serum follicle-stimulating hormone (FSH):
normal
More - serum oestradiol:
normal to elevated
More - serum thyroid-stimulating hormone:
normal
- serum prolactin:
normal
- serum 17-hydroxyprogesterone (17-OHP):
normal fasting levels help rule out 21-hydroxylase deficiency
More - serum dehydroepiandrosterone sulphate (DHEAS):
normal
- total serum testosterone:
elevated (>200 nanograms/dL; 6.94 nanomol/L)
More - pelvic ultrasound:
ovarian mass; variable endometrial echo-complex
Autoimmune premature ovarian failure
History
age <40 years, vasomotor symptoms, vaginal dryness, decreased libido, fatigue, weight gain
Exam
normal adult secondary sexual characteristics
1st investigation
- serum human chorionic gonadotropin:
negative
- serum follicle-stimulating hormone (FSH):
elevated (>25 units/L)
More - serum oestradiol:
low to undetectable
More - serum thyroid-stimulating hormone:
usually normal; associated autoimmunity may cause hypothyroidism (more common) or thyrotoxicosis
- serum prolactin:
usually normal, unless secondary elevation due to hypothyroidism
- serum free thyroxine (T4):
usually normal; associated autoimmunity may cause hypothyroidism (more common) or thyrotoxicosis
- serum thyroid antibodies:
may be present
More - morning serum cortisol:
may be low if Addison's disease present
- serum calcium:
may be low if autoimmune hypoparathyroidism present
- serum phosphorus:
may be elevated if autoimmune hypoparathyroidism present
- fasting serum glucose:
may be elevated if type 1 diabetes mellitus present
- pelvic ultrasound:
thin endometrial echo-complex
More
Other investigations
- serum LH:
elevated
More - 24-hour urine calcium:
may be low if autoimmune hypoparathyroidism present
- serum adrenal antibodies:
may be positive
More - serum inhibin:
low
More - karyotype (if age <30 years):
may suggest alternate diagnosis of gonadal dysgenesis
More - serum adrenocorticotrophin stimulation test:
may show lack of cortisol response if Addison's disease present
More - progestogen challenge test:
no withdrawal bleed
Androgen-producing adrenal tumour
History
rapidly progressive symptoms, obesity, hirsutism, acne, deepening voice, male-pattern hair growth or loss, oily skin, weight gain, oligoanovulatory cycles to amenorrhoea
Exam
androgenic alopecia, clitoromegaly, male-pattern hair growth, increased muscle mass
1st investigation
- serum human chorionic gonadotropin:
negative
- serum follicle-stimulating hormone (FSH):
normal
More - serum oestradiol:
normal to elevated
More - serum thyroid-stimulating hormone:
normal
- serum prolactin:
normal
- serum 17-hydroxyprogesterone (17-OHP):
normal fasting levels help to rule out 21-hydroxylase deficiency
More - serum dehydroepiandrosterone sulphate:
markedly elevated
- total serum testosterone:
elevated (>200 nanograms/dL; >6.94 nanomol/L)
More - pelvic ultrasound:
variable endometrial echo-complex
Cushing's syndrome
History
easily bruised, poor healing, weakness, weight gain, hirsutism, diabetes mellitus, hypertension, galactorrhoea (some patients), headache or visual disturbances (pituitary adenoma), may present with oligomenorrhoea
Exam
central obesity with thin extremities, nuchal fat pad, moon facies, purple striae
1st investigation
- serum human chorionic gonadotropin:
negative
- serum follicle-stimulating hormone (FSH):
normal
More - serum oestradiol:
normal to elevated
More - serum thyroid-stimulating hormone:
normal
- serum prolactin:
normal
- 24-hour urinary free cortisol:
elevated
- morning serum cortisol:
elevated
- serum adrenocorticotrophic hormone (ACTH):
elevated if Cushing's disease (pituitary) or ectopic source
- pelvic ultrasound:
variable endometrial echo-complex
Asherman's syndrome
History
amenorrhoea following an intrauterine procedure (dilatation and curettage for second-trimester abortion or pregnancy loss, or complication of post-procedural endometritis, myomectomy, caesarean delivery), moliminal symptoms (these are a useful clinical indicator of a normal reproductive cycle; they include increase in mid-cycle thin cervical secretions, and premenstrual symptoms such as menstrual cramps, breast tenderness, fluid retention, and mood or appetite changes)
Exam
normal adult secondary sexual characteristics and external genitalia
1st investigation
- serum human chorionic gonadotropin:
negative
- serum follicle-stimulating hormone (FSH):
normal
More - serum oestradiol:
normal
More - serum thyroid-stimulating hormone:
normal
- serum prolactin:
normal
- hysterosalpingogram:
irregular, scattered contour of contrast within the endometrial cavity, possible lack of contrast within oviducts due to obliterative process
More - pelvic ultrasound:
thin to variable endometrial echo-complex
More
Other investigations
- serum LH:
normal
More - diagnostic hysteroscopy:
obliterated endometrial cavity (variable)
- progestogen challenge test:
variable withdrawal bleed
Drug-induced
History
history of oral contraceptive use (however, this should not cause secondary amenorrhoea, as most users have return of function within 2 months of discontinuing), long-acting progestogens, androgens, antipsychotics (may down-regulate hypothalamic-pituitary-ovarian axis by way of dopaminergic pathways), or chronic cocaine or opioid use[19]
Exam
usually normal; some psychotropics may cause galactorrhoea
1st investigation
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