Hypogonadism

Hypogonadism
Classification and external resources
Specialty Endocrinology
ICD-10 E28.3,E29.1,E23.0
ICD-9-CM 257.2
OMIM 146110
DiseasesDB 21057
MedlinePlus 001195
eMedicine article/922038
MeSH D007006
GeneReviews

Hypogonadism means diminished functional activity of the gonads—the testes in males or the ovaries in females—that may result in diminished sex hormone biosynthesis. In layman's terms, it is sometimes called interrupted stage 1 puberty. Low androgen (e.g., testosterone) levels are referred to as hypoandrogenism and low estrogen (e.g., estradiol) as hypoestrogenism, and may occur as symptoms of hypogonadism in both sexes, but are generally only diagnosed in males and females respectively. Other hormones produced by the gonads that hypogonadism can decrease include progesterone, DHEA, anti-Müllerian hormone, activin, and inhibin. Spermatogenesis in males, and ovulation in females, may be impaired by hypogonadism, which, depending on the degree of severity, may result in partial or complete infertility.

Classification

Deficiency of sex hormones can result in defective primary or secondary sexual development, or withdrawal effects (e.g., premature menopause) in adults. Defective egg or sperm development results in infertility. The term hypogonadism usually means permanent rather than transient or reversible defects, and usually implies deficiency of reproductive hormones, with or without fertility defects. The term is less commonly used for infertility without hormone deficiency. There are many possible types of hypogonadism and several ways to categorize them. Hypogonadism is also categorized by endocrinologists by the level of the reproductive system that is defective. Physicians measure gonadotropins (LH and FSH) to distinguish primary from secondary hypogonadism. In primary hypogonadism the LH and/or FSH are usually elevated, meaning the problem is in the testicles, whereas in secondary hypogonadism, both are normal or low, suggesting the problem is in the brain.

Affected system

Primary or secondary

Congenital vs. acquired

Hormones vs. fertility

Hypogonadism can involve just hormone production or just fertility, but most commonly involves both.

Signs and symptoms

Women with hypogonadism do not begin menstruating and it may affect their height and breast development. Onset in women after puberty causes cessation of menstruation, lowered libido, loss of body hair and hot flashes. In boys it causes impaired muscle and beard development and reduced height. In men it can cause reduced body hair and beard, enlarged breasts, loss of muscle, and sexual difficulties. A brain tumor (central hypogonadism) may involve headaches, impaired vision, milky discharge from the breast and symptoms caused by other hormone problems.[3]

Hypogonadotrophic hypogonadism

The symptoms of hypogonadotrophic hypogonadism, a subtype of hypogonadism, include late, incomplete or lack of development at puberty, and sometimes short stature or the inability to smell; in females, a lack of breasts and menstrual periods, and in males a lack of sexual development, e.g., facial hair, penis and testes enlargement, deepening voice.

Diagnosis

Men

Low testosterone can be identified through a simple blood test performed by a laboratory, ordered by a physician. This test is typically ordered in the morning hours, when levels are highest, as levels can drop by as much as 13% during the day.[4]

Normal total testosterone levels range from 240–950 ng/dL (nanograms per decilitre)[5]

Treatment is often prescribed for total testosterone levels below 230 ng/dL.[6] If the serum total testosterone level is between 230 and 350 ng/dL, repeating the measurement of total testosterone with sex hormone-binding globulin (SHBG) to calculate free testosterone or free testosterone by equilibrium dialysis may be helpful.

The standard range given is based off widely varying ages and, given that testosterone levels naturally decrease as humans age, age-group specific averages should be taken into consideration when discussing treatment between doctor and patient.[7] In men, testosterone falls approximately 1 to 3 percent each year.[8]

Blood testing

A position statement by The Endocrine Society expressed dissatisfaction with most assays for TT (Total Testosterone) and FT (Free Testosterone).[9] In particular, research has questioned the validity of commonly administered assays of FT by RIA.[9] The FAI (Free Androgen Index) has been found to be the worst predictor of Free Testosterone.[10]

Women

Similar to men, the LH and FSH is used, particularly in women who believe they are in menopause. These levels change during a woman's normal menstrual cycle, so the history of having ceased menstruation coupled with high levels aids the diagnosis of being menopausal. Commonly, the post-menopausal woman is not called hypogonadal if she is of typical menopausal age. Contrast with a young woman or teen, who would have hypogonadism rather than menopause. This is because hypogonadism is an abnormality, whereas menopause is a normal change in hormone levels.

Hypogonadism is often discovered during evaluation of delayed puberty, but ordinary delay, which eventually results in normal pubertal development, wherein reproductive function is termed constitutional delay. It may be discovered during an infertility evaluation in either men or women.

Treatment

Male hypogonadism is most often treated with testosterone replacement therapy (TRT) in people who are not trying to conceive. Adverse effects of testosterone replacement therapy include increased cardiovascular events (including strokes and heart attacks) and deaths.[11] The Food and Drug Administration (FDA) stated in 2015 that neither the benefits nor the safety of testosterone have been established for low testosterone levels due to aging.[12][13] The FDA has required that testosterone pharmaceutical labels include warning information about the possibility of an increased risk of heart attacks and stroke.[12][13]

Commonly used testosterone replacement therapies include transdermal (through the skin) using a patch or gel, injections, or pellets. Oral testosterone is no longer used in the U.S. because it is broken down in the liver and rendered inactive; it also can cause severe liver damage. Like many hormonal therapies, changes take place over time. It may take as long as 2–3 months at optimum level to reduce the symptoms, particularly the wordfinding and cognitive dysfunction. Testosterone levels in the blood should be evaluated to ensure the increase is adequate. Levels between 400 and 700 ng/dL are considered appropriate mid-dose levels. Treatment usually starts with 200 mg intramuscular testosterone, repeated every 14 days.

While historically, men with prostate cancer risk were warned against testosterone therapy, that has shown to be a myth.[14]

Other side effects can include an elevation of the hematocrit to levels that require blood withdrawal (phlebotomy) to prevent complications from "too thick" blood. Another is that a man may have some growth in the size of the breasts (gynecomastia), though this is relatively rare. Finally, some physicians worry that Obstructive Sleep Apnea may worsen with testosterone therapy, and should be monitored.[15]

Another feasible treatment alternative is human chorionic gonadotropin (hCG).[16]

For both men and women, an alternative to testosterone replacement is Clomifene treatment, which can stimulate the body to naturally increase hormone levels while avoiding infertility and other side effects that can result from direct hormone replacement therapy.[17]

For men, Aquaviron injections may be useful.

For women, estradiol and progesterone are replaced. Some types of fertility defects can be treated, others cannot. Some physicians also give testosterone to women, mainly to increase libido.

See also

References

  1. ↑ MedlinePlus Encyclopedia Hypogonadotropic hypogonadism
  2. ↑ http://www.irondisorders.org/symptoms/
  3. ↑ MedlinePlus Encyclopedia Hypogonadism
  4. ↑ Crawford, E. David; Barqawi, Al Baha; O'Donnell, Colin; Morgentaler, Abraham (2007). "The association of time of day and serum testosterone concentration in a large screening population". BJU International. 100 (3): 509–13. doi:10.1111/j.1464-410X.2007.07022.x. PMID 17555474. Lay summary – UroToday (12 July 2007).
  5. ↑ MedlinePlus Encyclopedia Testosterone
  6. ↑ Nieschlag E, Swerdloff R, Behre HM, et al. (2006). "Investigation, treatment, and monitoring of late-onset hypogonadism in males: ISA, ISSAM, and EAU recommendations". Journal of Andrology. 27 (2): 135–7. doi:10.2164/jandrol.05047. PMID 16474020.
  7. ↑ http://www.mens-hormonal-health.com/normal-testosterone-levels.html
  8. ↑ School, Florence Comite, MD ; Foreword by Abraham Morgentaler, MD associate clinical professor of urology, Harvard Medical (2013). Keep it up : the power of precision medicine to conquer low T and revitalize your life. Rodale Books. p. 14. ISBN 978-1609611019.
  9. 1 2 Rosner W, Auchus RJ, Azziz R, Sluss PM, Raff H (February 2007). "Position statement: Utility, limitations, and pitfalls in measuring testosterone: an Endocrine Society position statement". The Journal of Clinical Endocrinology and Metabolism. 92 (2): 405–13. doi:10.1210/jc.2006-1864. PMID 17090633.
  10. ↑ Morris PD, Malkin CJ, Channer KS, Jones TH (August 2004). "A mathematical comparison of techniques to predict biologically available testosterone in a cohort of 1072 men". European Journal of Endocrinology. 151 (2): 241–9. doi:10.1530/eje.0.1510241. PMID 15296480.
  11. ↑ Finkle WD, Greenland S, Ridgeway GK, Adams JL, Frasco MA, Cook MB, Fraumeni JF, Hoover RN (January 2014). "Increased Risk of Non-fatal Myocardial Infarction Following Testosterone Therapy Prescription in Men" (PDF). PLoS ONE. 9 (1): e85805. doi:10.1371/journal.pone.0085805. PMC 3905977Freely accessible. PMID 24489673.
  12. 1 2 Staff (3 March 2015). "Testosterone Products: Drug Safety Communication - FDA Cautions About Using Testosterone Products for Low Testosterone Due to Aging; Requires Labeling Change to Inform of Possible Increased Risk of Heart Attack And Stroke". FDA. Retrieved 5 March 2015.
  13. 1 2 Tavernise, Sabrina (March 3, 2015). "Drugs Using Testosterone Will Label Heart Risks". New York Times. Retrieved March 19, 2015.
  14. ↑ Morgentaler (2006). "Testosterone and prostate cancer: an historical perspective on a modern myth". European Urology. 50 (5): 935–9. doi:10.1016/j.eururo.2006.06.034. PMID 16875775.
  15. ↑ Matsumoto, A. M.; Sandblom, R. E.; Schoene, R. B.; Lee, K. A.; Giblin, E. C.; Pierson, D. J.; Bremner, W. J. (1985-06-01). "Testosterone replacement in hypogonadal men: effects on obstructive sleep apnoea, respiratory drives, and sleep". Clinical Endocrinology. 22 (6): 713–721. doi:10.1111/j.1365-2265.1985.tb00161.x. ISSN 0300-0664. PMID 4017261.
  16. ↑ Chudnovsky, A.; Niederberger, C. S. (2007). "Gonadotropin Therapy for Infertile Men with Hypogonadotropic Hypogonadism". Journal of Andrology. 28 (5): 644–6. doi:10.2164/jandrol.107.003400. PMID 17522414.
  17. ↑ Whitten, S; Nangia, A; Kolettis, P (2006). "Select patients with hypogonadotropic hypogonadism may respond to treatment with clomiphene citrate". Fertility and Sterility. 86 (6): 1664–8. doi:10.1016/j.fertnstert.2006.05.042. PMID 17007848.
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