Differentiating menopause from other diseases

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Rahmah Al-Edresi, M.D.[2]

Overview

Menopause should be differentiated from other diseases presenting with menstrual irregularities (oligomenorrhea/amenorrhea).

Diseases	Onset	Manifestations					Diagnosis
		History and Symptoms				Physical examination	Laboratory findings	Gold standard	Imaging	Other investigation findings
		Trumatic delivery	Lactation failure	Menstrual irregularities	Other features
Sheehan's syndrome	Acute	++	++	Oligo/amenorrhea	Symptoms of: Adrenal insufficiency Hypothyroidism	Breast tissue atrophy Decreased axillary and pubic hair growth	Pancytopenia Eosinophilia Hyponatremia Low fasting plasma glucose Decreased levels of anterior pituitary hormones in blood	Clinical diagnosis Most senitive test: Low baseline prolactin levels w/o response to TRH	CT/MRI: Sequential changes of pituitary enlargement followed by: Shrinkage and necrosis leading to decreased sellar volume or empty sella	Pituitary hormone stimulation tests (Metoclopramide and clomiphene citrate stimulation tests)
Lymphocytic hypophysitis	Acute	+/-	+	Oligo/amenorrhea	Associated with autoimmune conditions Generalized headache Retro-orbital or Bitemporal pain Mass lesion effect such as visual field defects	DI Autoimmune thyroiditis	Decreased pituitary hormones(Gonadotropins most common) Hyperprolactinemia(40%) GH excess	Pituitary biopsy: lymphocytic infiltration	CT & MRI: Features of a pituitary mass Diffuse and homogeneous contrast enhancement	Assays for: Anti-TPO Anti-Tg Ab
Pituitary apoplexy	Acute	+/-	++	Oligo/amenorrhea	Severe headache Nausea and vomiting Paralysis of eye muscles (diplopia) Changes in vision	Visual acuity defects CN palsies (nerves III, IV, V , and VI)	Decreased levels of anterior pituitary hormones in blood.	MRI	CT scan without contrast: Hemorrhage on CT presents as a hyperdense lesion MRI: If inconclusive CT	Blood tests may be done to check: PT/INR and aPTT Pituitary hormonal assay
Empty sella syndrome	Chronic	-	+	Oligo/amenorrhea	Erectile dysfunction Headache Low libido	Signs of raised intracranial pressure may be present Nipple discharge	Decreased levels of pituitary hormones in the blood.	MRI	Empty sella containing CSF	Pituitary hormone stimulation tests (Metoclopramide and clomiphene citrate stimulation tests)
Simmonds' disease/Pituitary cachexia	Chronic	+/-	+	Oligo/amenorrhea	Cachexia Premature aging	Progressive emaciation Loss of body hair	Decreased levels of anterior pituitary hormones in the blood.	MRI	Done to rule out any pituitary cause	Pituitary hormone stimulation tests (Metoclopramide and clomiphene citrate stimulation tests)
Hypothyroidism	Chronic	+/-	-	Oligomenorrhea/menorrhagia	Cold intolerance Constipation	Dry skin Bradycardia Hair loss Myxedema Delayed relaxation phase of deep tendon reflexes	Low T3,T4 Normal/ low TSH Rest of pituitary hormone levels WNL	TSH levels	Done to rule out any pituitary cause	Assays for anti-TPO and anti-Tg Ab FNA biopsy
Hypogonadotropic hypogonadism	Chronic	-	-	Oligo/amenorrhea	Hot flushes Energy and mood changes Decreased libido	Breast tissue atrophy Decreased maturation of vaginal mucosa	Low estrogen, testosterone High FSH/LH	FSH LH	Done to rule out any pituitary cause	Genetic tests (karyotype) Measurement of total and free testosterone and 17-hydroxyprogesterone concentrations
Hypoprolactinemia	Chronic	-	+	-	Infertility Subfertility	Puerperal agalactogenesis	No workup is necessary	Decreased prolactin levels	Done to rule out any pituitary cause	Prolactin assay in 3rd trimester LH, FSH Thyrotropin and free thyroxine
Panhypopituitarism	Chronic	-	+	Oligo/amenorrhea	Polyuria Polydipsia Features of hypothyroidism and hypoadrenalism	Growth failure B/L hemianopsia Papilledema	All pituitary hormones decreased	MRI	Done to rule out any pituitary cause	Left hand and wrist radiograph for bone age
Primary adrenal insufficiency/Addison's disease	Chronic	-	-	-	Hypoglycemia Hypotension	Dehydration Hyperpigmentation loss of pubic and axillary hair	Hyponatremia with/without hyperkalemia Plasma renin activity to aldosterone ratio	Abdominal CT	Abdominal CT	Serum cortisol testing Serum ACTH testing Anti-adrenal Ab testing
Menopause	Chronic	-	+/-	Oligo/amenorrhea	Hot flashes Insomnia Weight gain and bloating Mood changes	Vaginal atrophy Loss of pelvic muscle tone	↑ FSH ↓ Estradiol and inhibin	FSH > LH	Normal	Endometrial biopsy

Diseases	Onset	Manifestations					Diagnosis
		History and Symptoms				Physical examination	Laboratory findings	Gold standard	Imaging	Other investigation findings
		Trumatic delivery	Lactation failure	Menstrual irregularities	Other features
Sheehan's syndrome	Acute	++	++	Oligo/amenorrhea	Symptoms of: Adrenal insufficiency Hypothyroidism	Breast tissue atrophy Decreased axillary and pubic hair growth	Pancytopenia Eosinophilia Hyponatremia Low fasting plasma glucose Decreased levels of anterior pituitary hormones in blood	Clinical diagnosis Most senitive test: Low baseline prolactin levels w/o response to TRH	CT/MRI: Sequential changes of pituitary enlargement followed by: Shrinkage and necrosis leading to decreased sellar volume or empty sella	Pituitary hormone stimulation tests (Metoclopramide and clomiphene citrate stimulation tests)
Lymphocytic hypophysitis	Acute	+/-	+	Oligo/amenorrhea	Associated with autoimmune conditions Generalized headache Retro-orbital or Bitemporal pain Mass lesion effect such as visual field defects	DI Autoimmune thyroiditis	Decreased pituitary hormones(Gonadotropins most common) Hyperprolactinemia(40%) GH excess	Pituitary biopsy: lymphocytic infiltration	CT & MRI: Features of a pituitary mass Diffuse and homogeneous contrast enhancement	Assays for: Anti-TPO Anti-Tg Ab
Pituitary apoplexy	Acute	+/-	++	Oligo/amenorrhea	Severe headache Nausea and vomiting Paralysis of eye muscles (diplopia) Changes in vision	Visual acuity defects CN palsies (nerves III, IV, V , and VI)	Decreased levels of anterior pituitary hormones in blood.	MRI	CT scan without contrast: Hemorrhage on CT presents as a hyperdense lesion MRI: If inconclusive CT	Blood tests may be done to check: PT/INR and aPTT Pituitary hormonal assay
Empty sella syndrome	Chronic	-	+	Oligo/amenorrhea	Erectile dysfunction Headache Low libido	Signs of raised intracranial pressure may be present Nipple discharge	Decreased levels of pituitary hormones in the blood.	MRI	Empty sella containing CSF	Pituitary hormone stimulation tests (Metoclopramide and clomiphene citrate stimulation tests)
Simmonds' disease/Pituitary cachexia	Chronic	+/-	+	Oligo/amenorrhea	Cachexia Premature aging	Progressive emaciation Loss of body hair	Decreased levels of anterior pituitary hormones in the blood.	MRI	Done to rule out any pituitary cause	Pituitary hormone stimulation tests (Metoclopramide and clomiphene citrate stimulation tests)
Hypothyroidism	Chronic	+/-	-	Oligomenorrhea/menorrhagia	Cold intolerance Constipation	Dry skin Bradycardia Hair loss Myxedema Delayed relaxation phase of deep tendon reflexes	Low T3,T4 Normal/ low TSH Rest of pituitary hormone levels WNL	TSH levels	Done to rule out any pituitary cause	Assays for anti-TPO and anti-Tg Ab FNA biopsy
Hypogonadotropic hypogonadism	Chronic	-	-	Oligo/amenorrhea	Hot flushes Energy and mood changes Decreased libido	Breast tissue atrophy Decreased maturation of vaginal mucosa	Low estrogen, testosterone High FSH/LH	FSH LH	Done to rule out any pituitary cause	Genetic tests (karyotype) Measurement of total and free testosterone and 17-hydroxyprogesterone concentrations
Hypoprolactinemia	Chronic	-	+	-	Infertility Subfertility	Puerperal agalactogenesis	No workup is necessary	Decreased prolactin levels	Done to rule out any pituitary cause	Prolactin assay in 3rd trimester LH, FSH Thyrotropin and free thyroxine
Panhypopituitarism	Chronic	-	+	Oligo/amenorrhea	Polyuria Polydipsia Features of hypothyroidism and hypoadrenalism	Growth failure B/L hemianopsia Papilledema	All pituitary hormones decreased	MRI	Done to rule out any pituitary cause	Left hand and wrist radiograph for bone age
Primary adrenal insufficiency/Addison's disease	Chronic	-	-	-	Hypoglycemia Hypotension	Dehydration Hyperpigmentation loss of pubic and axillary hair	Hyponatremia with/without hyperkalemia Plasma renin activity to aldosterone ratio	Abdominal CT	Abdominal CT	Serum cortisol testing Serum ACTH testing Anti-adrenal Ab testing
Menopause	Chronic	-	+/-	Oligo/amenorrhea	Hot flashes Insomnia Weight gain and bloating Mood changes	Vaginal atrophy Loss of pelvic muscle tone	↑ FSH ↓ Estradiol and inhibin	FSH > LH	Normal	Endometrial biopsy