Algorithm(s)
PDF algorithm(s) available at www.arupconsult.com.
Primary Amenorrhea Testing Algorithm
Secondary Amenorrhea Testing Algorithm
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 in the absence of secondary sexual characteristics or age 16 if secondary sexual characteristics are present
- Etiology (most common)
- Androgen insensitivity
- Congenital adrenal hyperplasia
- Congenital anomalies
- Constitutional delayed puberty
- Eating disorder
- Excessive exercise
- Gonadal dysgenesis
- Turner syndrome (diagnose by chromosome analysis)
- Hyperprolactinemia
- Primary ovarian failure
- Secondary - have secondary sexual characteristics and previous menstrual flow but no menstrual flow for 3 months in women with previously normal menstruation or for 9 months in women with previous oligomenorrhea
- Etiology (most common)
- Polycystic ovarian syndrome (PCOS)
- Hypothyroidism
- Hyperprolactinemia
- Eating disorder, excessive exercise
- Pituitary disease
- Depression
- Ovarian failure
- Medication-induced
- Antidepressants
- Antipsychotics
- Chemotherapy
- Tumor
- Pituitary
- Craniopharyngioma
- Fragile X syndrome
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 can result in amenorrhea
Clinical Presentation
- Primary - may have absence of secondary sexual characteristics or congenital anomalies of the urogenital system
- Secondary - body habitus consistent with PCOS, anorexic body habitus, galactorrhea, excessive facial hair
See Also
Algorithm(s)
PDF algorithm(s) available at www.arupconsult.com.
Primary Amenorrhea Testing Algorithm
Secondary Amenorrhea Testing Algorithm
Diagnosis
Diagnosis
- Indications for testing - presence of amenorrhea without identifiable cause
- Laboratory testing
- Exclude pregnancy - urinary or serum BHCG
- Initial evaluation of secondary amenorrhea - FSH, LH, prolactin, estrogen, thyroid stimulating hormone
- Initial evaluation of primary amenorrhea - TSH, prolactin, LH, FSH
- Secondary evaluation - may include testosterone, dehydroepiandrosterone, sulfate (DHEAS) and estradiol
- Chromosome analysis for X chromosome abnormalities
- Imaging studies
- Pelvic ultrasound (US), transvaginal US
- Head MRI
Differential Diagnosis
- Most common diseases to rule out are in the prior section titled "Classifications"
- Thyroid disease
- Pregnancy
Algorithm(s)
PDF algorithm(s) available at www.arupconsult.com.
Primary Amenorrhea Testing Algorithm
Secondary Amenorrhea Testing Algorithm
Tests generally appear in the order most useful for common clinical situations
| Test name: Prolactin
|
| ARUP #: 0070115 |
| Methodology: Chemiluminescent Immunoassay
|
| Use: Distinguish amenorrhea from prolactinemia |
| Limitations: |
| Follow-up:
|
| Test name: Luteinizing Hormone and Follicle Stimulating Hormone
|
| ARUP #: 0070193 |
| Methodology: Electrochemiluminescent Immunoassay
|
| Use: Diagnose amenorrhea |
| Limitations: |
| Follow-up:
|
| Test name: Estradiol, Adult Premenopausal Female, Serum or Plasma
|
| ARUP #: 0070045 |
| Methodology: Chemiluminescent Immunoassay
|
| Use: Diagnose secondary amenorrhea |
| Limitations: |
| Follow-up:
|
| Test name: Testosterone, Free & Total (Includes Sex Hormone Binding Globulin), Females or Children
|
| ARUP #: 0081056 |
Methodology: Tandem Mass Spectrometry
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.
|
| Use: Diagnose secondary amenorrhea |
| Limitations: |
| Follow-up:
|
| Test name: Dehydroepiandrosterone Sulfate, Serum
|
| ARUP #: 0070040 |
| Methodology: Electrochemiluminescent Immunoassay
|
| Use: Diagnose secondary amenorrhea |
| Limitations: |
| Follow-up:
|
| Test name: Thyroid Stimulating Hormone
|
| ARUP #: 0070145 |
| Methodology: Electrochemiluminescent Immunoassay
|
| Use: Monitor amenorrhea |
| Limitations: |
| Follow-up:
|
| Test name: Chromosome Analysis, Peripheral Blood
|
| ARUP #: 0097640 |
| Methodology: Giemsa-Band Analysis
|
| Use: Detection of X chromosome abnormalities |
| Limitations: Will not identify tissue-specific mosaicism not present in peripheral blood |
| Test name: Immunohistochemistry Stain Offering
|
| ARUP #: arup005 |
| Methodology: Immunohistochemistry
|
| Use: For fixed tissue samples, consultative services as well as immunohistochemical staining for prolactin are available |
Additional Tests Available
| Test name: Estrogens, Fractionated by Tandem Mass Spectrometry
|
| ARUP #: 0093248 |
| Methodology: Liquid Chromatography/Tandem Mass Spectrometry/Calculation
|
| Comments: Diagnose amenorrhea |
| Test name: Follicle Stimulating Hormone, Serum
|
| ARUP #: 0070055 |
| Methodology: Electrochemiluminescent Immunoassay
|
| Comments: |
| Test name: Luteinizing Hormone, Pooled
|
| ARUP #: 0020780 |
| Methodology: Electrochemiluminescent Immunoassay
|
| Comments: |
| Test name: Testosterone, Bioavailable & Sex Hormone Binding Globulin (Includes Total Testosterone), Females or Children
|
| ARUP #: 0081057 |
Methodology: High Performance Liquid Chromatography/Tandem Mass Spectrometry
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.
|
| Comments: |
| Test name: Testosterone Free, Females or Children
|
| ARUP #: 0081059 |
Methodology: Tandem Mass Spectrometry
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.
|
| Comments: |
| Test name: Testosterone, Females or Children
|
| ARUP #: 0081058 |
| Methodology: High Performance Liquid Chromatography/Tandem Mass Spectrometry
|
| Comments: |
| Test name: Estradiol, Males, Children or Postmenopausal Females, by Tandem Mass Spectrometry
|
| ARUP #: 0093247 |
| Methodology: Liquid Chromatography/Tandem Mass Spectrometry
|
| Comments: |
| Test name: Estrone, by Tandem Mass Spectrometry
|
| ARUP #: 0093249 |
| Methodology: Liquid Chromatography/Tandem Mass Spectrometry
|
| Comments: |
References
General References
Bloomfield D. Secondary amenorrhea. Pediatr Rev.
2006;
27(
3):
113-114.
Broekmans FJ, Fauser BC. Diagnostic criteria for polycystic ovarian syndrome. Endocrine.
2006;
30(
1):
3-11.
Goswami D, Conway GS. Premature ovarian failure. Hum Reprod Update.
2005;
11(
4):
391-410.
Martin JR, Arici A. Fragile X and reproduction. Curr Opin Obstet Gynecol.
2008;
20(
3):
216-220.
Master-Hunter T, Heiman DL. Amenorrhea: evaluation and treatment. Am Fam Physician.
2006;
73(
8):
1374-1382.
Rudolph LM. Cytogenetics of Infertility. In: Gersen SL, Keagle MB, ed. The Principles of Clinical Cytogenetics.Totowa, NJ, 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.
Current evaluation of amenorrhea. Fertil Steril.
2006;
86(
5 Suppl):
S148-S155.
Medical Reviewers
Lamb, Allen N., Ph.D. Medical Director, Cytogenetics, ARUP Laboratories; Associate Professor, Department of Pathology, University of Utah
Meikle, A. Wayne, M.D. Medical Director, RIA and Endocrinology at ARUP Laboratories; Professor of Internal Medicine and Pathology, University of Utah
Perkins, Sherrie L. , M.D., Ph.D. Medical Director, Hematopathology at ARUP Laboratories; Professor, Anatomic Pathology, University of Utah
Roberts, William L. , M.D., Ph.D. Medical Director, Automated Core Laboratory at ARUP Laboratories; Professor, Pathology, University of Utah
South, Sarah T. , Ph.D. Medical Director, Cytogenetics at ARUP Laboratories; Assistant Medical Director, CGH Microarray Laboratory, and Assistant Professor, Department of Pediatrics, University of Utah
Comprehensive Review: May 2008
Last Update: July 2008
