Amenorea Arup

The Physician's Guide to Laboratory Test Selection and Interpretation
Amenorrhea
Clinical Background
Amenorrhea is defined as the absence of menstrual flow.

Epidemiology
Prevalence 3-4% when not due to pregnancy, lactation or menopause
Secondary amenorrhea more common than primary amenorrhea
Classifications
Primary lack of menstrual flow by age 14 and absence of secondary sexual characteristics or lack of
menstrual flow by age 16 and presence of secondary sexual characteristics
Etiology (most common)
Gonadal dysgenesis/agenesis
Turner syndrome
Enzymatic deficiencies
Congenital adrenal hyperplasia
Congenital anomalies (includes vaginal, cervical and uterine etiologies)
Constitutional delayed puberty
Eating disorder
Excessive exercise
Hyperprolactinemia
Primary ovarian failure
Androgen insensitivity
Polycystic ovarian syndrome (PCOS)
Secondary presence of secondary sexual characteristics and previous menstrual flow but no menstrual
flow for 3 months in women with previously normal menstruation or no menstrual flow for 9 months in
women with previous oligomenorrhea
Etiology (most common)
Polycystic ovarian syndrome (PCOS)
Hypothyroidism
Pituitary disease
Hyperprolactinemia
Eating disorder
Excessive exercise
Depression
Ovarian failure
Medication-induced
Antidepressants
Antipsychotics
Chemotherapy
Oral contraceptives
Tumor
Pituitary
Craniopharyngioma
Fragile X syndrome
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Amenorrhea - p. 1 of 6
Pathophysiology
Normal menses require developed endometrium, normal outflow tract and functioning
hypothalamic-pituitary-ovarian axis
Hypothalamus secretes gonadotropin releasing hormone (GnRH) causing anterior pituitary release of
follicle stimulating hormone (FSH) and luteinizing hormone (LH)
LH and FSH surge stimulates the ovary to secrete estrogen, progestin and androgen
FSH causes a follicle to be dominant and release an ovum (thought to be from LH spike)
Progestin from corpus luteum suppresses FSH and LH
Without fertilization, the corpus luteum involutes, estrogen and progestin levels fall and menses occur
Interruption in pathway at any point can result in amenorrhea
Clinical Presentation
Primary may have absence of secondary sexual characteristics or congenital anomalies of the
urogenital system
Secondary variable body habitus consistent with PCOS, anorexic body habitus, galactorrhea, hirsutism
Diagnosis
Indications for testing presence of amenorrhea without identifiable cause

Laboratory testing
Urinary or serum beta human chorionic gonadotropin (BHCG) exclude pregnancy
Initial evaluation of secondary amenorrhea FSH, LH, prolactin, estrogen, thyroid stimulating
hormone (TSH)
Elevated FSH, LH suggests ovarian abnormality
Normal or low FSH, LH suggests pituitary or hypothalamic abnormality
Initial evaluation of primary amenorrhea TSH, prolactin, LH, FSH
Secondary evaluation may include testosterone, dehydroepiandrosterone sulfate (DHEAS) and
estradiol measurements
Chromosome analysis for X chromosome abnormalities may be necessary
Imaging studies
Pelvic ultrasound (US) or transvaginal US (TVUS)
Head MRI
Differential Diagnosis
Most of the common diseases in the differential are found in the prior section titled "Classifications"
Thyroid disease
Pregnancy
Lab Tests
Indications for Laboratory Testing

Tests generally appear in the order most useful for common clinical situations. For test-specific information, refer to the
test number in the ARUP Laboratory Test Directory on the ARUP Web site at www.aruplab.com.
Test Name and Number
Recommended Use
Beta-hCG, Urine
Qualitative
0020229
Exclude pregnancy
Method:
Immunoassay
Beta-hCG, Serum
Qualitative
0020063
Exclude pregnancy
Method:
Immunoassay
Luteinizing Hormone
and Follicle Stimulating
Hormone
0070193
Diagnose amenorrhea
Method:
Electrochemiluminescent
Immunoassay
Prolactin
0070115
Method:
Chemiluminescent
Immunoassay
Thyroid Stimulating
Hormone
0070145
Method:
Immunoassay
Estradiol, Adult
Premenopausal Female,
Serum or Plasma
0070045
Limitations
Follow Up
Identify prolactinemia as etiology of

amenorrhea
Rule out thyroid disease as etiology

of amenorrhea
Aid in evaluation of secondary

amenorrhea
Method:
Chemiluminescent
Immunoassay
Testosterone, Free & Total

(Includes Sex Hormone
Binding Globulin),
Females or Children
0081056
Method:
High Performance Liquid
Chromatography/Tandem
Mass Spectrometry/
Immunoassay
The concentration of free
testosterone is derived
from a mathematical
expression based on the
constant for the binding
of testosterone to sex
hormone binding globulin.
Dehydroepiandrosterone
Sulfate, Serum
0070040

amenorrhea

amenorrhea
Method:
Immunoassay
Additional Tests Available
Test Name and Number
Comments
Estrogens, Fractionated by Tandem Mass Spectrometry

0093248
Diagnose amenorrhea
Method:
Liquid Chromatography/Tandem Mass
Spectrometry/Calculation
Virilization Panel 1
2002028
Method:
Liquid Chromatography/Tandem Mass Spectrometry
Virilization Panel 2
2002281
Method:
High Performance Liquid Chromatography/Tandem Mass
Spectrometry
Follicle Stimulating Hormone, Serum
0070055
Method:
Electrochemiluminescent Immunoassay
Luteinizing Hormone, Pooled

0020780
Method:
Electrochemiluminescent Immunoassay
Testosterone, Bioavailable & Sex Hormone Binding Globulin
(Includes Total Testosterone), Females or Children
0081057
Method:
Spectrometry/Electrochemiluminescent Immunoassay
The concentrations of free and bioavailable testosterone are
derived from mathematical expressions based on constants
for the binding of testosterone to albumin and/or sex hormone
binding globulin.
Testosterone Free, Females or Children
0081059
Test recommended for women and children due to

improved accuracy of testosterone by LC-MS/MS
Method:
Spectrometry/Electrochemiluminescent Immunoassay
The concentration of free testosterone is derived from a
mathematical expression based on the constant for the
binding of testosterone to sex hormone binding globulin.
Testosterone, Females or Children
0081058
Method:
Spectrometry
Estradiol, Males, Children or Postmenopausal Females, by
Tandem Mass Spectrometry
0093247
Method:
Liquid Chromatography/Tandem Mass Spectrometry
Fragile X (FMR1) Screen with Reflex to Fragile X (FMR1)
Diagnostic
2001946
Method:
Polymerase Chain Reaction/Fragment Analysis
Fragile X (FMR1) Diagnostic
0040011
Method:
Southern Blot/Polymerase Chain Reaction/Fragment Analysis
Chromosome Analysis, Rule Out Mosaicism
2002287
Method:
Giemsa-Band Analysis
General References
Bloomfield D. Secondary amenorrhea.Pediatr Rev. 2006; 27 (3) :113-114.
Current evaluation of amenorrhea.Fertil Steril. 2006; 86 (5 Suppl) :S148-S155.

Goswami D, Conway GS. Premature ovarian failure.Hum Reprod Update. 2005; 11 (4) :391-410.
Master-Hunter T, Heiman DL. Amenorrhea: evaluation and treatment.Am Fam Physician. 2006; 73 (8) :1374-1382.
Practice Committee of the American Society fro Reproductive Medicine Current evaluation of amenorrhea.Fertil Steril.
2008; 90 (5 Suppl) :S219-S225.
Rudolph LM. Cytogenetics of Infertility. In Gersen SL, Keagle MB, eds. The Principles of Clinical Cytogenetics. Totowa,
New Jersey: Humana Press Inc, 2005. pp. 247-265.
Warren MP, Hagey AR. The genetics, diagnosis and treatment of amenorrhea.Minerva Ginecol. 2004; 56 (5) :437-455.
Wilson GR, Haddad JE, Haddad CJ. Amenorrhea: common causes and evaluation.Compr Ther. 2005; 31 (4)
:270-278.
Reviewed by
Meikle, A. Wayne, MD. Medical Director, RIA and Endocrinology at ARUP Laboratories; Professor of Internal Medicine
and Pathology, University of Utah
Perkins, Sherrie L., MD, PhD. Director of Laboratories, Chief Medical Officer, and Medical Director, Hematopathology,
at ARUP Laboratories; Professor of Anatomic Pathology, University of Utah
Roberts, William L., MD, PhD. Medical Director, Automated Core Laboratory at ARUP Laboratories; Professor of
Pathology, University of Utah
South, Sarah T., PhD. Medical Director, Cytogenetics and Molecular Cytogenetics at ARUP Laboratories; Assistant
Professor, Department of Pediatrics, Adjunct Professor, Department of Pathology, University of Utah
Diagnostic Algorithm(s)
PDF algorithm(s) available at www.arupconsult.com.
Primary Amenorrhea Testing Algorithm
Secondary Amenorrhea Testing Algorithm
Related Content
Adrenal Hyperfunction - Cushing Syndrome
Hypopituitarism
Infertility
Polycystic Ovarian Syndrome
Comprehensive Review: May 2009
Last Update: November 2009

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The Physician's Guide to Laboratory Test Selection and Interpretation

Amenorrhea is defined as the absence of menstrual flow.

The Physician's Guide to Laboratory Test Selection and Interpretation

Indications for testing presence of amenorrhea without identifiable cause

The Physician's Guide to Laboratory Test Selection and Interpretation

Indications for Laboratory Testing

Identify prolactinemia as etiology of

Rule out thyroid disease as etiology

Aid in evaluation of secondary

The Physician's Guide to Laboratory Test Selection and Interpretation

Testosterone, Free & Total

Aid in evaluation of secondary

Aid in evaluation of secondary

Estrogens, Fractionated by Tandem Mass Spectrometry

The Physician's Guide to Laboratory Test Selection and Interpretation

Luteinizing Hormone, Pooled

Test recommended for women and children due to

The Physician's Guide to Laboratory Test Selection and Interpretation

Current evaluation of amenorrhea.Fertil Steril. 2006; 86 (5 Suppl) :S148-S155.

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