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Follicle-Stimulating Hormone (FSH) 

  • Author: Alina G Sofronescu, PhD; Chief Editor: Thomas M Wheeler, MD  more...
 
Updated: Jul 16, 2015
 

Reference Range

Age-specific, gender-specific, and, for women, menstrual cycle phase-specific reference intervals have been established.

The reference range for follicle-stimulating hormone (FSH) is as follows (3rd generation immunochemiluminescence assay):

Females

  • Age 0-7 years: <6.7 mIU/mL 
  • Age 8 years to adult:
    • Follicular phase: 3.1-7.9 mIU/mL
    • Ovulation peak: 2.3-18.5 mIU/mL
    • Luteal phase: 1.4-5.5 mIU/mL
    • Postmenopausal: 30.6-106.3 mIU/mL

Males

  • Age 0-7 years: <6.7 mIU/mL
  • Age 8 years-adult:1.3-19.3 mIU/mL
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Interpretation

Conditions associated with increased FSH include primary hypogonadism, either congenital or acquired:

Conditions associated with decreased FSH include the following secondary or tertiary causes of hypogonadism, either congenital or acquired:

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Collection and Panels

Preferred specimen and acceptable tubes:

  • Serum (red top tube, SST)
  • Plasma (green top tube - sodium heparin, ammonium heparin, lithium heparin; PST)

Specimen volume: 0.5 mL plasma or serum (0.1 mL minimum volume)

Specimen stability: 

  • Centrifuge specimens and remove serum or plasma from the cells within 2 hours of the collection
  • Store at room temperature for 8 hours, or refrigerate at 2-8 degrees Celsius (36-46 degrees Fahrenheit) up to 5 days. 
  • If assays are not completed within 48 hours, or the separated sample is to be stored beyond 48 hours, samples should be frozen at -20 degrees Celsius or colder. Frozen samples should be thawed only once. Analyte deterioration may occur in samples that are repeatedly frozen and thawed.

Sample collection

Because of the cyclic and circadian variations in the secretion of gonadotropins, a meaningful evaluation of FSH and LH requires either testing of a pool of blood specimens collected 20-30 min apart or average the hormone measurements of multiple blood samples collected 20-30 min apart.

Related tests:

Usually, for a better and rapid evaluation of hypothalamic-pituitary-gonadal axis, both FSH and LH are evaluated together in the same sample and in the same time and most of the modern assays are using cocktails of antibodies for both FSH and LH, allowing their concurrent evaluation.

Measurement of FSH

There are 2 major ways in which FSH is currently evaluated: radioimmunoassay (RIA) and chemiluminescence immunoassays.

In the RIA, endogenous FSH present in the sample is competing with iodine radiolabeled FSH for a limited amount of FSH-specific antibodies (“competitive assay”). The measured signal is inversely proportional with the amount of TSH present in the sample.

The chemiluminescence assay is using two antibodies (“sandwich immunoassay”). The “capture antibody” is usually binding the alpha subunit of FSH, while the “detection antibody” is always binding within the FSH-specific beta-subunit. The measured signal is directly proportional with the amount of FSH present in the sample. The chemiluminescence assay is significantly more sensitive than RIA.[2]  

As all immunoassays, these assays are prone to specific interferences, especially heterophilic antibodies. Hook effect is rarely seen. Interferences from other hormones with similar biochemical structure (eg, LH, TSH, hCG) and from free alpha subunits produced by some pituitary tumors were eliminated by using antibodies specifically directed against beta-subunit epitopes of FSH. However, epitope specificity was not yet achieved, and intense efforts are placed into standardization of the FSH assay.[4]

Measurement of FSH in urine

Because of the cyclic and circadian variations in the secretion of gonadotropins, it is difficult to overcome the issue of detection sensitivity using randomly collected blood samples, especially in children and prepubertal teens. Therefore, more and more pediatric endocrinologists support the idea of FSH and LH evaluation 3-hour urine collection. The kidneys integrate the episodic secretion of these hormones and the urine samples can be further concentrated, so the issue of detection sensitivity and variability can be overcome.[4]  

In women with PCOS, the concentration of FSH is low relative to the concentration of LH, with an increased ratio of LH to FSH. A ratio LH to FSH greater than 2.5 is often used for the diagnosis of PCOS.[5]

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Background

Description

The anterior pituitary gland produces two gonadotropins: follicle-stimulating hormone (FSH) and luteinizing hormone (LH).

FSH (see the image below) is a glycoprotein secreted by the anterior pituitary in response to gonadotropin-releasing hormone (GnRH), which, in turn, it is released by the hypothalamus.

Follicle stimulating hormone, beta polypeptide. Follicle stimulating hormone, beta polypeptide.

Structurally, FSH and LH are composed of an alpha and a beta subunits. While alpha subunit is identical between gonadotropins TSH and hCG, the specific beta subunit confers the unique biologic activity. Upon release in circulation, FSH binds to G-protein coupled receptors in the testicular Sertoli cells and ovarian granulosa cells. Through this, FSH promotes spermatogenesis and secretion of inhibins in males, while in females, it stimulates the proliferation of the granulosa cells, development of a dominant follicle, expression of LH receptors, and secretion of estrogen and inhibins. In their turn, inhibins provide feedback centrally to the hypothalamus, and, in this way, they are also inhibiting the secretion of FSH. Together, these hormones and target organs form the “hypothalamic-pituitary-gonadal axis." Therefore, FSH is essential for reproduction in males and females.[4]  

The hypothalamic-pituitary-gonadal axis in men and The hypothalamic-pituitary-gonadal axis in men and women.

Conditions related to LH and FSH abnormalities can be caused by pathology of either the hypothalamus or pituitary. Careful analysis of the presenting problem, the patient’s overall health, and the hormonal profile is often necessary to determine the cause of FSH abnormality and, thus, the most appropriate treatment.[4, 6, 7]

Assessment of FSH, LH, and additional hormones (eg, sex steroids, prolactin, thyroid hormones) is useful in evaluation of hypogonadism, delayed puberty, infertility, polycystic ovarian syndrome (PCOS), amenorrhea, and hypothalamic-pituitary dysfunctions.

Indications/Applications

Indications for testing of FSH include the following:

  • Evaluating menstrual irregularities (including anovulatory bleeding)
  • Evaluating suspected hypogonadism
  • Evaluating precocious puberty
  • Predicting ovulation
  • Evaluating infertility
  • Evaluating pituitary disorders
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Contributor Information and Disclosures
Author

Alina G Sofronescu, PhD Assistant Professor, Board Certified Clinical Chemist, Technical Director of Clinical Chemistry Laboratory, Department of Pathology and Microbiology, University of Nebraska Medical Center

Alina G Sofronescu, PhD is a member of the following medical societies: American Association for Clinical Chemistry, Canadian Society of Clinical Chemists

Disclosure: Nothing to disclose.

Chief Editor

Thomas M Wheeler, MD Chairman, Department of Pathology and Immunology, WL Moody, Jr, Professor of Pathology, Professor of Urology, Baylor College of Medicine

Thomas M Wheeler, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for Cancer Research, American Medical Association, American Society for Clinical Pathology, American Society of Cytopathology, American Thyroid Association, American Urological Association, College of American Pathologists, United States and Canadian Academy of Pathology, International Society of Urological Pathology, Harris County Medical Society

Disclosure: Received stock from PathXL for medical advisory board. for: PathXL, Inc.

References
  1. Busch AS, Tuttelmann F, Zitzmann M, Kliesch S, Gromoll J. The FSHB -T variant attenuates serum FSH levels in the supraphysiological gonadotropin setting of Klinefelter syndrome. Eur J Hum Genet. 2015 May. 23 (5):700-3. [Medline].

  2. Papaleo E, Alviggi C, Colombo GL, Pisanelli C, Ripellino C, Longobardi S, et al. Cost-effectiveness analysis on the use of rFSH + rLH for the treatment of anovulation in hypogonadotropic hypogonadal women. Ther Clin Risk Manag. 2014. 10:479-84. [Medline].

  3. Tsakos E, Tolikas A, Daniilidis A, Asimakopoulos B. Predictive value of anti-müllerian hormone, follicle-stimulating hormone and antral follicle count on the outcome of ovarian stimulation in women following GnRH-antagonist protocol for IVF/ET. Arch Gynecol Obstet. 2014 Dec. 290 (6):1249-53. [Medline].

  4. Burris CA, Ashwood ER, Burns DE. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 4th ed. St Louis: Elsevier Saunders; 2006.

  5. Clarke W. Contemporary Practice in Clinical Chemistry. 2nd ed. Washington DC: 2010.

  6. Jabbour SA. Follicle-Stimulating Hormone Abnormalities. Medscape Drugs & Diseases. Available at http://emedicine.medscape.com/article/118810-overview. Jan 3, 2012; Accessed: Feb 15, 2012.

  7. McPherson RA, Matthew R, Pincus MR. Henry's Clinical Diagnosis and Management by Laboratory Methods. 22nd ed. Philadelphia: Elsevier Saunders; 2011. 254-5.

  8. Trabado S, Maione L, Bry-Gauillard H, Affres H, Salenave S, Sarfati J, et al. Insulin-like peptide 3 (INSL3) in men with congenital hypogonadotropic hypogonadism/Kallmann syndrome and effects of different modalities of hormonal treatment: a single-center study of 281 patients. J Clin Endocrinol Metab. 2014 Feb. 99 (2):E268-75. [Medline].

 
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Follicle stimulating hormone, beta polypeptide.
The hypothalamic-pituitary-gonadal axis in men and women.
 
 
 
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