Amenorrhea differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Eiman Ghaffarpasand, M.D. [2], Mehrian Jafarizade, M.D [3]

Overview

As amenorrhea manifests in a variety of clinical forms, differentiation must be established in accordance with the particular subtype. Primary amenorrhea must be differentiated from other diseases that cause lack of menstrual cycle, such as Mullerian agenesis, 3-beta-hydroxysteroid dehydrogenase type 2 deficiency, androgen insensitivity syndrome, Kallmann syndrome, Turner syndrome, and 17-alpha-hydroxylase deficiency. In contrast, secondary amenorrhea must be differentiated from other diseases that cause menstrual cycle arrest, such as primary ovarian insufficiency, hypothyroidism, hyperprolactinemia, polycystic ovary syndrome, and Asherman’s syndrome.

As amenorrhea manifests in a variety of clinical forms, differentiation must be established in accordance with the particular subtype. Primary amenorrhea must be differentiated from other diseases that cause lack of menstrual cycle, such as Mullerian agenesis, 3-beta-hydroxysteroid dehydrogenase type 2 deficiency, androgen insensitivity syndrome, Kallmann syndrome, Turner syndrome, and 17-alpha-hydroxylase deficiency. In contrast, secondary amenorrhea must be differentiated from other diseases that cause menstrual cycle arrest, such as primary ovarian insufficiency, hypothyroidism, hyperprolactinemia, polycystic ovary syndrome, and Asherman’s syndrome.

Group	Diseases	Laboratory Findings										Physical Examination				Other Findings
Group	Diseases	Estrogen	Progesterone	GnRH	LH	FSH	Androgen	TSH	T4	PRL	Karyotype	Externl genitalia	Breast development	Pubic hair	Uterus	Other Findings
Primary amenorrhea	Mullerian agenesis^[1]	Nl	Nl	Nl	Nl	Nl	Nl	Nl	Nl	Nl	46 XX	Nl	+	+	–	Urinary tract defects Fused vertebrae
	3-beta-hydroxysteroid dehydrogenase type 2 deficiency	Nl	Nl	Nl	Nl	Nl	↓	Nl	Nl	Nl	46 XX	Clitoromegaly	-/+	+	+	Hyponatremia Hypokalemia
	Androgen insensitivity syndrome^[2]	Nl	Nl	↓	↑	Nl	↑↑	Nl	Nl	Nl	46 XY	Nl	+	+	–	Undescended testis
	Kallmann syndrome^[3]	↓	↓	↓↓	↓	↓	↓	Nl	Nl	Nl	46 XX	Nl	–	–	+	Anosmia/Hyposmia
	Turner syndrome^[4]	↓↓	↓	↑	↑	↑	Nl	Nl	Nl	Nl	45 XO	Nl	+/-	+	+	Webbed neck Cardiac defects
	17-alpha-hydroxylase deficiency	↓	Nl	↑	↑	↑	↓	Nl	Nl	Nl	46 XY	Infantilism	–	–	–	Hypertension
Secondary amenorrhea	Primary ovarian insufficiency^[5]	↓↓	↓	↑	↑	↑	Nl	Nl	Nl	Nl	46 XX	Nl	+	+	+	Osteoporosis Ischemic heart disease
	Hypothyroidism^[6]	Nl	Nl	Nl	Nl	Nl	↑	↑↑	↓↓	Nl	46 XX	Nl	+	+	+	Fatigue Decreased deep tendon reflexes (DTR)
	Hyperprolactinemia^[7]	↓	↓	↓	↓	↓	↓	Nl	Nl	↑	46 XX	Nl	+	+	+	Galactorrhea Headaches Visual disturbances
	Polycystic ovary syndrome^[8]	↓↓	↓↓	↑	↑	↑	↑	Nl	Nl	Nl	46 XX	Nl	+	+	+	Hirsutism Insulin resistance
	Asherman’s syndrome^[9]	Nl	Nl	Nl	Nl	Nl	Nl	Nl	Nl	Nl	46 XX	Nl	+	+	+	History of uterus surgery Uterus scarring

↑ Folch M, Pigem I, Konje JC (2000). “Müllerian agenesis: etiology, diagnosis, and management”. Obstet Gynecol Surv. 55 (10): 644–9. PMID 11023205.
↑ “Current evaluation of amenorrhea”. Fertil. Steril. 82 (1): 266–72. 2004. doi:10.1016/j.fertnstert.2004.02.098. PMID 15237040.
↑ Albanese A, Stanhope R (1995). “Investigation of delayed puberty”. Clin. Endocrinol. (Oxf). 43 (1): 105–10. PMID 7641400.
↑ Sybert VP, McCauley E (2004). “Turner’s syndrome”. N. Engl. J. Med. 351 (12): 1227–38. doi:10.1056/NEJMra030360. PMID 15371580.
↑ Nelson LM (2009). “Clinical practice. Primary ovarian insufficiency”. N. Engl. J. Med. 360 (6): 606–14. doi:10.1056/NEJMcp0808697. PMC 2762081. PMID 19196677.
↑ Kalro BN (2003). “Impaired fertility caused by endocrine dysfunction in women”. Endocrinol. Metab. Clin. North Am. 32 (3): 573–92. PMID 14575026.
↑ Pickett CA (2003). “Diagnosis and management of pituitary tumors: recent advances”. Prim. Care. 30 (4): 765–89. PMID 15024895.
↑ “ACOG practice bulletin clinical management guidelines for obstetrician-gynecologists. Number 40, November 2002”. Obstet Gynecol. 100 (5 Pt 1): 1045–50. 2002. PMID 12434783.
↑ Fritz, Marc (2011). Clinical gynecologic endocrinology and infertility. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. ISBN 978-0781779685.