Amenorrhea laboratory findings
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Eiman Ghaffarpasand, M.D. [2]
Overview
Initial laboratory tests for evaluating amenorrhea include pregnancy test, thyroid stimulating hormone (TSH), follicle stimulating hormone (FSH), and prolactin (PRL). Second line laboratory tests include free and total testosterone, dehydroepiandrosterone sulfate (DHEAS), and also progesterone challenge test.
Laboratory Findings
- Initial laboratory tests for evaluating amenorrhea include pregnancy test, thyroid stimulating hormone (TSH), follicle stimulating hormone (FSH), and prolactin (PRL).[1]
- Second line laboratory tests include free and total testosterone, dehydroepiandrosterone sulfate (DHEAS), and progesterone challenge test.
| Disease | Laboratory tests | ||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Pregnancy test | TSH | T4 | Anti-TPO Ab | Anti-TSH-R Ab | PRL | LH | FSH | Estradiol | Prog. | Testosterone | DHEAS | AD | 17-OH-prog. | Insulin | FBS | Insulin resistance indexes | ACTH | Cortisol | Markers of ovarian tumors | Prog. challenge test | Leptin | Inhibin | |
| Pregnancy | Positive | β | β | +/- | – | β | – | – | – | β | – | – | – | – | – | – | – | – | – | – | – | – | – |
| Hypothyroidism | – | ββ | β | +/- | – | – | – | – | β | β | – | – | – | – | – | – | – | – | – | – | – | – | – |
| Hyperthyroidism | – | ββ | β | – | – | – | – | – | β | β | – | – | – | – | – | – | – | – | – | – | – | – | – |
| Thyroiditis | – | ββ | ββ | Positive | – | – | – | – | β | β | – | – | – | – | – | – | – | – | – | – | – | – | – |
| Graves’ disease | – | ββ | βββ | – | Positive | – | – | – | β | β | – | – | – | – | – | – | – | – | – | – | – | – | – |
| Hyperprolactinemia | – | – | – | – | – | ββ | β | β | β | β | – | – | – | – | – | – | – | – | – | – | – | – | – |
| Prolactinoma | – | β | β | – | – | βββ | ββ | ββ | β | β | – | – | – | – | – | – | – | – | – | – | – | – | – |
| Hypothalamic disease | – | ββ | ββ | – | – | ββ | ββ | ββ | ββ | ββ | – | – | – | – | – | – | – | – | – | – | – | ββ | – |
| Premature ovarian failure | – | – | – | – | – | – | ββ | ββ | ββ | ββ | – | – | – | β | – | – | – | – | – | – | – | – | ββ |
| Androgen insensitivity syndrome | – | – | – | – | – | – | ββ | ββ | βββ | βββ | β | β | β | – | – | – | – | – | – | – | – | – | – |
| Polycystic ovary syndrome (PCOS) | – | – | – | – | – | – | β | β | β | β | β | β | β | – | β | β | β | – | – | – | Positive | – | – |
| Congenital adrenal hyperplasia (CAH) | – | – | – | – | – | – | β | β | β | β | – | – | – | β | – | – | – | – | β | – | – | – | – |
| ACTH-secreting adenoma | – | – | – | – | – | β | ββ | ββ | ββ | ββ | – | – | – | – | – | – | – | β | β | – | – | – | – |
| Ovarian adenocarcinoma | – | – | – | – | – | – | β | β | β | β | – | – | – | – | – | – | – | – | – | Positive | – | – | – |
| HPO axis immaturity | – | – | – | – | – | – | ββ | ββ | ββ | ββ | – | – | – | – | – | – | – | – | – | – | Positive | – | – |
| Imperforate hymen | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – |
| Asherman’s syndrome | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – | – |
| Abbreviations: TSH: Hemoglobin, T4: Thyroxin, Anti-TPO Ab: Anti-thyroid peroxidase antibodies, Anti-TSH-R Ab: Anti-thyroidΒ stimulating hormone antibodies, PRL: Prolactin, LH: Luteinizing hormone, FSH: Follicle stimulating hormone, Prog.: Progesterone, DHEAS: Dehydroepiandrosterone sulfate, AD: Delta 4-androstenedione, 17-OH-Prog.: 17-hydroxyprogesterone, FBS: Fasting blood sugar, ACTH: Adrenocorticotropic hormone, HPO axis: Hypothalamus-pituitary-ovary axis. | |||||||||||||||||||||||
Biochemical Tests
Urine or serum pregnancy test
- Some patients with amenorrhea may have positive urine or serum pregnancy test, which is usually suggestive of pregnancy-induced amenorrhea.[2]
Thyroid function tests
- Thyroid function tests in patients of amenorrhea include:[3]
- Elevated TSH and reduced free thyroxine (T4), suggestive of hypothyroidism.
- Reduced TSH and elevated T4, suggestive of hyperthyroidism.
- Elevated anti-thyroglobulin antibodies and anti-thyroid peroxidase antibodies, suggestive of thyroiditis.
- Elevated anti-thyrotropin receptor antibodies, suggestive of Graves’ disease.
Prolactin (PRL)
- Some patients with amenorrhea may have elevated concentration of prolactin, which is usually suggestive of amenorrhea due to hyperprolactinemia (may be due to pituitary causes, such as prolactinoma).[4][5]
Basal plasma gonadotropins
- Basal plasma gonadotropins in patients of amenorrhea include:
- Reduced luteinizing hormone (LH) and FSH, suggestive of hypothalamic and pituitary diseases or premature ovarian failure.[6][7]
- Reduced LH, suggestive of complete androgen insensitivity syndrome.[8]
Estradiol
- Estradiol interpretation in patients of amenorrhea include:
- Reduced estradiol, suggestive of ovarian failure or pituitary causes.[7][9]
- Elevated estradiol, suggestive of androgen insensitivity syndrome.
Progesterone
- Some patients with amenorrhea may have reduced concentration of progesterone, which is usually suggestive of ovarian failure.[10]
Free and total testosterone
- Some patients with amenorrhea may have elevated concentration of testosterone, which is usually suggestive of amenorrhea due to complete androgen insensitivity syndrome.[8]
Dehydroepiandrosterone sulfate (DHEAS)
- Some patients with amenorrhea may have elevated concentration of dehydroepiandrosterone sulfate (DHEAS), which is usually suggestive of amenorrhea due to polycystic ovary syndrome (PCOS).[11]
Delta 4-androstenedione
- Some patients with amenorrhea may have elevated concentration of delta 4-androstenedione, which is usually suggestive of amenorrhea due to polycystic ovary syndrome (PCOS).[12]
17-hydroxyprogesterone
- Some patients with amenorrhea may have elevated concentration of 17-hydroxyprogesterone, which is usually suggestive of amenorrhea due to congenital adrenal hyperplasia (CAH).[6]
Fasting insulin
- Some patients with amenorrhea may have elevated concentration of fasting insulin, which is usually suggestive of amenorrhea due to polycystic ovary syndrome (PCOS).[13]
Fasting glucose (FBS)
- Some patients with amenorrhea may have elevated concentration of fasting glucose (FBS), which is usually suggestive of amenorrhea due to polycystic ovary syndrome (PCOS).
Insulin resistance indexes
- Some patients with amenorrhea may have elevated insulin resistance indexes, which is usually suggestive of amenorrhea due to polycystic ovary syndrome (PCOS).
Adrenocorticotropic hormone (ACTH)
- Some patients with amenorrhea may have elevated concentration of adrenocorticotropic hormone (ACTH), which is usually suggestive of amenorrhea due to pituitary causes (ACTH-secreting adenoma).
Cortisol
- Some patients with amenorrhea may have elevated concentration of cortisol, which is usually suggestive of amenorrhea due to pituitary causes (ACTH-secreting adenoma).
Markers of ovarian tumors
- Some patients with amenorrhea may have elevated concentration of markers of ovarian tumors, which is usually suggestive of ovarian failure (due to adenocarcinoma).
Progesterone challenge test
- Progesterone challenge test is used in secondary amenorrhea with normal female androgen in order to measure circulating estrogen. It reveals the insufficient endometrial estrogenization.
- It is consisted of Provera 10 mg PO for 7 days and then following for bleeding. If patient bleed it means that estrogen is repleted, hypothalamic-pituitary-ovarian (HPO) axis immaturity or PCOS.[6]
Leptin
- Some patients with amenorrhea may have reduced concentration of leptin, which is usually suggestive of amenorrhea due to hypothalamic disorders.[14]
Inhibin
- Some patients with amenorrhea may have reduced concentration of inhibin, which is usually suggestive of amenorrhea due to ovarian failure.[9]
References
- β Pereira K, Brown AJ (2017). “Secondary amenorrhea: Diagnostic approach and treatment considerations”. Nurse Pract. 42 (9): 34β41. doi:10.1097/01.NPR.0000520832.14406.76. PMIDΒ 28832422.
- β Master-Hunter T, Heiman DL (2006). “Amenorrhea: evaluation and treatment”. Am Fam Physician. 73 (8): 1374β82. PMIDΒ 16669559.
- β Rebar RW, Connolly HV (1990). “Clinical features of young women with hypergonadotropic amenorrhea”. Fertil. Steril. 53 (5): 804β10. PMIDΒ 2110072.
- β Patel, S. S.; Bamigboye, V. (2009). “Hyperprolactinaemia”. Journal of Obstetrics and Gynaecology. 27 (5): 455β459. doi:10.1080/01443610701406125. ISSNΒ 0144-3615.
- β “Hyperprolactinemia and Associated Pituitary Prolactinomas.Β : Obstetrics & Gynecology”.
- β 6.0 6.1 6.2 Deligeoroglou, Efthimios; Athanasopoulos, Nikolaos; Tsimaris, Pandelis; Dimopoulos, Konstantinos D.; Vrachnis, Nikolaos; Creatsas, G. (2010). “Evaluation and management of adolescent amenorrhea”. Annals of the New York Academy of Sciences. 1205 (1): 23β32. doi:10.1111/j.1749-6632.2010.05669.x. ISSNΒ 0077-8923.
- β 7.0 7.1 Santoro N (2003). “Mechanisms of premature ovarian failure”. Ann. Endocrinol. (Paris). 64 (2): 87β92. PMIDΒ 12773939.
- β 8.0 8.1 Hughes, Ieuan A.; Deeb, Asma (2006). “Androgen resistance”. Best Practice & Research Clinical Endocrinology & Metabolism. 20 (4): 577β598. doi:10.1016/j.beem.2006.11.003. ISSNΒ 1521-690X.
- β 9.0 9.1 Beck-Peccoz P, Persani L (2006). “Premature ovarian failure”. Orphanet J Rare Dis. 1: 9. doi:10.1186/1750-1172-1-9. PMCΒ 1502130. PMIDΒ 16722528.
- β Timmreck, Lorna S.; Reindollar, Richard H. (2003). “Contemporary issues in primary amenorrhea”. Obstetrics and Gynecology Clinics of North America. 30 (2): 287β302. doi:10.1016/S0889-8545(03)00027-5. ISSNΒ 0889-8545.
- β Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO (2004). “The prevalence and features of the polycystic ovary syndrome in an unselected population”. J. Clin. Endocrinol. Metab. 89 (6): 2745β9. doi:10.1210/jc.2003-032046. PMIDΒ 15181052.
- β Boomsma CM, Eijkemans MJ, Hughes EG, Visser GH, Fauser BC, Macklon NS (2006). “A meta-analysis of pregnancy outcomes in women with polycystic ovary syndrome”. Hum. Reprod. Update. 12 (6): 673β83. doi:10.1093/humupd/dml036. PMIDΒ 16891296.
- β Teede H, Deeks A, Moran L (2010). “Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan”. BMC Med. 8: 41. doi:10.1186/1741-7015-8-41. PMCΒ 2909929. PMIDΒ 20591140.
- β Welt, Corrine K.; Chan, Jean L.; Bullen, John; Murphy, Robyn; Smith, Patricia; DePaoli, Alex M.; Karalis, Aspasia; Mantzoros, Christos S. (2004). “Recombinant Human Leptin in Women with Hypothalamic Amenorrhea”. New England Journal of Medicine. 351 (10): 987β997. doi:10.1056/NEJMoa040388. ISSNΒ 0028-4793.
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