Medscape is available in 5 Language Editions – Choose your Edition here.


Follicle-Stimulating Hormone Abnormalities Workup

  • Author: Serge A Jabbour, MD, FACP, FACE; Chief Editor: George T Griffing, MD  more...
Updated: Jul 12, 2016

Laboratory Studies

Perform additional laboratory studies in men presenting with low follicle-stimulating hormone (FSH) levels.

  • Regarding LH and testosterone, most patients with low FSH levels also have low LH and low testosterone levels. A few cases of isolated FSH deficiency exist in which LH and testosterone levels are within reference ranges but the sperm count is low.
  • For prolactin, patients with high prolactin levels frequently manifest low FSH, LH, and testosterone levels, all of which may resolve with normalization of prolactin levels.
  • In men with low FSH levels and feminizing features, including gynecomastia, serum estradiol measurement is indicated to exclude an estrogen-secreting tumor (testes, adrenals).
  • Semen analysis is performed to assess fertility.

In men presenting with high FSH levels, the underlying etiology is related to primary hypogonadism or a gonadotroph adenoma. Therefore, the following lab tests are indicated:

  • For LH and testosterone, patients with primary hypogonadism have low testosterone levels with high LH and FSH levels. Patients with gonadotroph adenomas usually have high FSH levels with normal LH and testosterone levels; occasionally, LH levels can be high, but testosterone levels are also high. Gonadotroph adenomas that secrete FSH may induce compression of normal pituitary cells, leading to low LH and testosterone levels.
  • In patients with gonadotroph adenomas, other pituitary hormone levels must also be assessed because macroadenomas may induce hypopituitarism. Serum TSH and free T4, morning cortisol and adrenocorticotropic hormone (ACTH), prolactin, and, occasionally, dynamic testing for GH may be necessary.
  • Obtain a peripheral leukocyte karyotype in men with congenital primary hypogonadism to determine if Klinefelter syndrome is present.

In women presenting with low FSH levels, additional testing should include determination of LH, estradiol, and prolactin levels. Thyroid disease should be excluded by measuring TSH and free T4. If hirsutism is present, serum testosterone and dehydroepiandrosterone sulfate (DHEAS) testing should be performed. Moreover, additional testing such as determination of the serum 17-hydroxyprogesterone level before and after ACTH stimulation may be performed if congenital adrenal hyperplasia is suggested.

In women with high FSH levels, the differential diagnosis is either ovarian failure or gonadotroph adenoma. The following points should be remembered:

  • In women with ovarian failure, both FSH and LH levels rise. In women with gonadotroph adenomas, FSH levels are usually high, but LH levels remain within reference ranges. Other pituitary hormone abnormalities may be present.
  • If the diagnosis of ovarian failure is confirmed in patients younger than 30 years, a karyotype evaluation should be performed to exclude Turner syndrome or the presence of Y chromatin material because of the high risk of gonadal tumors, mandating gonadectomy.
  • In the presence of a normal karyotype, autoimmune disease is likely (30% of these patients); therefore, assessment for autoimmune disorders, including thyroid or adrenal disease, is important. Testing may include TSH, antithyroid antibodies, morning serum cortisol, and ACTH evaluations, followed by an ACTH stimulation test if necessary.

Imaging Studies

In men or women with low follicle-stimulating hormone (FSH), high prolactin, or high FSH levels (the latter being suggestive of gonadotroph adenoma in the appropriate clinical setting), an MRI scan of the pituitary gland must be obtained.

In women with very high DHEAS levels (>700 mcg/dL), perform CT scanning of the adrenals to exclude an androgen-secreting tumor.

In women with very high testosterone levels (>200 ng/mL), perform imaging studies of the ovaries (CT scan, ultrasound).

In men with high estradiol levels, imaging of the testes (ultrasound) should be performed and, subsequently, the adrenals (CT scan) if the testicular ultrasound findings are normal.



In women with clinical features and laboratory findings suggestive of an ovarian tumor but with negative results from imaging studies, laparoscopy may be performed to help locate ovarian masses, which could be small and are frequently difficult to detect using routine imaging.

Contributor Information and Disclosures

Serge A Jabbour, MD, FACP, FACE Professor of Medicine, Division of Endocrinology, Diabetes and Metabolic Diseases, Jefferson Medical College of Thomas Jefferson University

Serge A Jabbour, MD, FACP, FACE is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians-American Society of Internal Medicine, American Diabetes Association, American Medical Association, American Thyroid Association, Endocrine Society, Pennsylvania Medical Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Romesh Khardori, MD, PhD, FACP Professor of Endocrinology, Director of Training Program, Division of Endocrinology, Diabetes and Metabolism, Strelitz Diabetes and Endocrine Disorders Institute, Department of Internal Medicine, Eastern Virginia Medical School

Romesh Khardori, MD, PhD, FACP is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, American Diabetes Association, Endocrine Society

Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD Professor Emeritus of Medicine, St Louis University School of Medicine

George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, International Society for Clinical Densitometry, Southern Society for Clinical Investigation, American College of Medical Practice Executives, American Association for Physician Leadership, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society

Disclosure: Nothing to disclose.

  1. Grover A, Smith CE, Gregory M, et al. Effects of FSH receptor deletion on epididymal tubules and sperm morphology, numbers, and motility. Mol Reprod Dev. 2005 Oct. 72(2):135-44. [Medline].

  2. Karges B, de Roux N. Molecular genetics of isolated hypogonadotropic hypogonadism and Kallmann syndrome. Endocr Dev. 2005. 8:67-80. [Medline].

  3. Fraietta R, Zylberstejn DS, Esteves SC. Hypogonadotropic hypogonadism revisited. Clinics (Sao Paulo). 2013. 68 Suppl 1:81-8. [Medline]. [Full Text].

  4. Otto AP, Franca MM, Correa FA, et al. Frequent development of combined pituitary hormone deficiency in patients initially diagnosed as isolated growth hormone deficiency: a long term follow-up of patients from a single center. Pituitary. 2015 Aug. 18(4):561-7. [Medline].

  5. Nagorny P, Sane N, Fasching B, Aussedat B, Danishefsky SJ. Probing the Frontiers of Glycoprotein Synthesis: The Fully Elaborated ß-Subunit of the Human Follicle-Stimulating Hormone. Angew Chem Int Ed Engl. 2011 Dec 9. [Medline].

  6. Dandona P, Dhindsa S, Chaudhuri A, et al. Hypogonadotrophic hypogonadism in type 2 diabetes. Aging Male. 2008 Sep. 11(3):107-17. [Medline].

  7. Ferhi K, Avakian R, Griveau JF, et al. Age as only predictive factor for successful sperm recovery in patients with Klinefelter's syndrome. Andrologia. 2009 Apr. 41(2):84-7. [Medline].

  8. Wikstrom AM, Dunkel L. Testicular function in Klinefelter syndrome. Horm Res. 2008. 69(6):317-26. [Medline].

  9. Van Saen D, Gies I, De Schepper J, Tournaye H, Goossens E. Can pubertal boys with Klinefelter syndrome benefit from spermatogonial stem cell banking?. Hum Reprod. 2011 Dec 12. [Medline].

  10. Desai SS, Roy BS, Mahale SD. Mutations and polymorphisms in FSH receptor: functional implications in human reproduction. Reproduction. 2013 Dec. 146(6):R235-48. [Medline].

  11. Cools M, Rooman RP, Wauters J, et al. A nonmosaic 45,X karyotype in a mother with Turner's syndrome and in her daughter. Fertil Steril. 2004 Oct. 82(4):923-5. [Medline].

  12. Livadas S, Xekouki P, Kafiri G, et al. Spontaneous pregnancy and birth of a normal female from a woman with Turner syndrome and elevated gonadotropins. Fertil Steril. 2005 Mar. 83(3):769-72. [Medline].

  13. Ardawi MS, Rouzi AA. Plasma adiponectin and insulin resistance in women with polycystic ovary syndrome. Fertil Steril. 2005 Jun. 83(6):1708-16. [Medline].

  14. Walvoord E. Sex steroid replacement for induction of puberty in multiple pituitary hormone deficiency. Pediatr Endocrinol Rev. 2009 Jan. 6 Suppl 2:298-305. [Medline].

  15. Trabado S, Maione L, Salenave S, Baron S, Galland F, Bry-Gauillard H, et al. Estradiol levels in men with congenital hypogonadotropic hypogonadism and the effects of different modalities of hormonal treatment. Fertil Steril. 2011 Jun. 95(7):2324-9, 2329.e1-3. [Medline].

  16. Efesoy O, Cayan S, Akbay E. The efficacy of recombinant human follicle-stimulating hormone in the treatment of various types of male factor infertility at a single university hospital. J Androl. 2009 May 28. [Medline]. [Full Text].

  17. Zhang M, Tong G, Liu Y, et al. Sequential Versus Continual Purified Urinary FSH/hCG in Men With Idiopathic Hypogonadotropic Hypogonadism. J Clin Endocrinol Metab. 2015 Jun. 100(6):2449-55. [Medline].

  18. Andersson AM, Jorgensen N, Frydelund-Larsen L, et al. Impaired Leydig cell function in infertile men: a study of 357 idiopathic infertile men and 318 proven fertile controls. J Clin Endocrinol Metab. 2004 Jul. 89(7):3161-7. [Medline]. [Full Text].

  19. Aron DC, Findling JW, Tyrrell JB. Hypothalamus & Pituitary. Greenspan FS, Strewler GJ, eds. Basic & Clinical Endocrinology. 5th ed. New York, NY: McGraw-Hill; 1997. 112-4.

  20. Bachmann G. Physiologic aspects of natural and surgical menopause. J Reprod Med. 2001 Mar. 46(3 Suppl):307-15. [Medline].

  21. Cevik R, Gur A, Acar S, et al. Hypothalamic-pituitary-gonadal axis hormones and cortisol in both menstrual phases of women with chronic fatigue syndrome and effect of depressive mood on these hormones. BMC Musculoskelet Disord. 2004 Dec 8. 5(1):47. [Medline].

  22. Conway GS. Premature ovarian failure. Br Med Bull. 2000. 56(3):643-9. [Medline].

  23. Fraser IS, Kovacs G. Current recommendations for the diagnostic evaluation and follow-up of patients presenting with symptomatic polycystic ovary syndrome. Best Pract Res Clin Obstet Gynaecol. 2004 Oct. 18(5):813-23. [Medline].

  24. Gur A, Cevik R, Nas K, et al. Cortisol and hypothalamic-pituitary-gonadal axis hormones in follicular-phase women with fibromyalgia and chronic fatigue syndrome and effect of depressive symptoms on these hormones. Arthritis Res Ther. 2004. 6(3):R232-8. [Medline].

  25. Hayes FJ, Seminara SB, Crowley WF Jr. Hypogonadotropic hypogonadism. Endocrinol Metab Clin North Am. 1998 Dec. 27(4):739-63, vii. [Medline].

  26. Ishikawa T, Fujioka H, Fujisawa M. Clinical and hormonal findings in testicular maturation arrest. BJU Int. 2004 Dec. 94(9):1314-6. [Medline].

  27. Klibanski A. Nonsecreting pituitary tumors. Endocrinol Metab Clin North Am. 1987 Sep. 16(3):793-804. [Medline].

  28. Lamberts SW, de Herder WW, van der Lely AJ. Pituitary insufficiency. Lancet. 1998 Jul 11. 352(9122):127-34. [Medline].

  29. McDonough PG. Molecular abnormalities of FSH and LH action. Ann N Y Acad Sci. 2003 Nov. 997:22-34. [Medline].

  30. McIver B, Romanski SA, Nippoldt TB. Evaluation and management of amenorrhea. Mayo Clin Proc. 1997 Dec. 72(12):1161-9. [Medline].

  31. Plymate S. Hypogonadism. Endocrinol Metab Clin North Am. 1994 Dec. 23(4):749-72. [Medline].

  32. Practice Committee of the American Society for Reproductive Medicine. Current evaluation of amenorrhea. Fertil Steril. 2004 Jul. 82(1):266-72. [Medline].

  33. Silber SJ. Evaluation and treatment of male infertility. Clin Obstet Gynecol. 2000 Dec. 43(4):854-88. [Medline].

  34. Wang C, Swerdloff RS. Androgen replacement therapy. Ann Med. 1997 Oct. 29(5):365-70. [Medline].

  35. Women''s Health Initiative. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women''s Health Initiative randomized controlled trial. JAMA. 2002 Jul 17. 288(3):321-33. [Medline].

  36. Young J, Chanson P, Salenave S, et al. Testicular anti-mullerian hormone secretion is stimulated by recombinant human FSH in patients with congenital hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 2005 Feb. 90(2):724-8. [Medline].

Human G protein-coupled receptor 54 (GPR54) receptor model. Mutations identified in patients with idiopathic hypogonadotropic hypogonadism are indicated.
This is a frequently sampled serum luteinizing hormone (LH) profile in a male patient with Kallmann syndrome (KS), compared with that in a healthy individual. A lack of LH pulsatility is seen in the former.
Magnetic resonance imaging (MRI) scan of pituitary macroadenoma.
Adolescent male with Klinefelter syndrome who has female-type distribution of pubic hair, as well as testicular dysgenesis.
Hypoplastic right hemiscrotum in a patient with an undescended right testis.
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.