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Clinical features and diagnosis of male hypogonadism

Clinical features and diagnosis of male hypogonadism
Literature review current through: Jan 2024.
This topic last updated: May 05, 2022.

INTRODUCTION — The clinical features of male hypogonadism are sufficiently well recognized, the causes sufficiently well known, and the tests of the hypothalamic-pituitary-testicular axis sufficiently accurate to permit the diagnosis in most patients.

This topic will review the major clinical features and diagnostic approach to hypogonadism in adult men. The causes and management of primary and secondary male hypogonadism and an overview of hypogonadism in older men are reviewed elsewhere. (See "Causes of primary hypogonadism in males" and "Causes of secondary hypogonadism in males" and "Testosterone treatment of male hypogonadism" and "Approach to older males with low testosterone".)

BACKGROUND — Hypogonadism in a male refers to a decrease in one or both of the two major functions of the testes: sperm production or testosterone production. These abnormalities can result from disease of the testes (primary hypogonadism) or disease of the hypothalamus or pituitary (secondary hypogonadism). The distinction between these disorders, which will be described below, is made by measurement of the serum concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH):

The patient has primary hypogonadism if the serum testosterone concentration and/or the sperm count are below normal and the serum LH and/or FSH concentrations are above normal.

The patient has secondary hypogonadism if the serum testosterone concentration and/or the sperm count are below normal and the serum LH and/or FSH concentrations are normal or low.

In primary hypogonadism, spermatogenesis tends to be impaired to a greater degree than Leydig cell function, at least in its early stages. In contrast, both functions are impaired to the same degree in secondary hypogonadism (figure 1).

Spermatogenesis cannot be increased in men with primary hypogonadism, because of damage to the seminiferous tubules. However, successful pregnancies have now been reported with men with primary hypogonadism, including men with Klinefelter syndrome, using sperm extracted from the testes with subsequent in vitro fertilization by intracytoplasmic sperm injection (see "Treatments for male infertility", section on 'Retrieval of sperm'). In contrast, treatment with gonadotropins can often restore spermatogenesis in men with secondary hypogonadism. (See "Induction of fertility in males with secondary hypogonadism".)

CLINICAL FEATURES — The clinical features of male hypogonadism depend upon the age of onset, severity of testosterone deficiency, and whether there is a decrease in one or both of the two major functions of the testes: sperm production and testosterone production.

There are several possible clinical manifestations of testosterone deficiency, which are determined by its time of onset during reproductive development (table 1).

Time of onset — A clinician should obtain an account of the developmental milestones of sexual development, current symptoms, and information about possible causes of hypogonadism (table 2 and table 3). (See "Causes of primary hypogonadism in males" and "Causes of secondary hypogonadism in males".)

Specific abnormalities of sexual development may indicate both the cause and the time of the hypogonadism (table 1):

First trimester – Ambiguous genitalia in a male at birth indicates deficient testosterone production or androgen action during the first trimester. Complete lack of testosterone production or androgen action during this period results in female external genitalia (clitoris and labia). Incomplete testosterone deficiency or androgen action causes partial virilization, ranging from posterior labioscrotal fusion and micropenis when the deficiency is severe, to simply hypospadias when it is mild. (See "Evaluation of the infant with atypical genital appearance (difference of sex development)" and "Pathogenesis and clinical features of disorders of androgen action".)

Third trimester – Micropenis at birth suggests deficient testosterone production in the third trimester. Bilateral cryptorchidism is usually associated with diminished spermatogenesis and sometimes with low testosterone in adulthood. (See "Typical sex development", section on 'Development of the male phenotype' and "Undescended testes (cryptorchidism) in children: Clinical features and evaluation".)

Prepubertal – When the onset of testosterone deficiency occurs at any time after birth during the first decade, the result is failure to undergo or complete puberty. (See "Approach to the patient with delayed puberty".)

Adult – When testosterone deficiency first occurs after completion of puberty, symptoms may include a decrease in energy and libido that occurs within days to weeks. However, sexual hair, muscle mass, and bone mineral density usually do not diminish to a significant degree for several years, although profound deficiency may cause a more rapid decline. Adults may also present with infertility. (See "Etiology of osteoporosis in men" and "Causes of male infertility".)

Symptoms — Because testosterone affects many tissues, lack of testosterone can cause many different symptoms. In adults, the symptoms are likely to be worse if the hypogonadism develops over the course of weeks or months than slowly over years.

Adolescents and young adults who have not yet completed puberty appear younger than their chronologic age. They may also present with small genitalia, difficulty gaining muscle mass in spite of vigorous exercise, lack of a beard, and failure of the voice to deepen. (See "Approach to the patient with delayed puberty".)

In adult men, several common but nonspecific symptoms begin within a few weeks of the onset of testosterone deficiency: decreased vigor and libido and depressed mood [1]. Decreased muscle mass and body hair are less common but do not occur for a year or many years. Hot flashes occur only when the degree of hypogonadism is severe and especially when the rate of fall is rapid. Gynecomastia, tender or not, is more likely to occur in primary than secondary hypogonadism, as is infertility.

Physical findings — There are a number of signs on physical examination that provide strong evidence of hypogonadism. The physical examination should focus first on whether or not the patient is normally virilized and has normal genitalia. If either is abnormal, the exam should then be directed toward clues as to whether the hypogonadism is primary or secondary and if it began before or after puberty.

Males who develop hypogonadism before the onset of puberty and are not treated do not develop body hair and a beard characteristic of other men in the family, temporal hair recession, full male musculature, or deep voice. Men who develop hypogonadism after puberty may lose these characteristics if the hypogonadism is severe enough and/or of sufficient duration, usually years.

Males who develop hypogonadism before the onset of puberty have small testes (<20 mL) and a small phallus (<8 cm) (table 4). If hypogonadism develops after puberty, the testes usually decrease in size if the hypogonadism is primary, which preferentially damages the seminiferous tubules, but they usually do not decrease to a recognizable degree if it is secondary. The phallus does not decrease in size.

Gynecomastia, the presence of glandular breast tissue in a male, is more likely to occur in primary than secondary hypogonadism. (See "Epidemiology, pathophysiology, and causes of gynecomastia" and "Clinical features, diagnosis, and evaluation of gynecomastia in adults".)

Finding eunuchoid proportions in an adult male at any age indicates that the hypogonadism developed prepubertally. Eunuchoid proportions include a lower body segment (floor to pubis) that is more than 2 cm longer than upper body segment (pubis to crown) and an arm span that is more than 5 cm longer than height. In comparison, a normal adult male has approximately equal upper and lower body segments as well as arm span and height. The absence of testosterone (and as a result, estradiol) during puberty causes a delay in epiphyseal closure so that the continued presence of growth hormone results in an increase in the length of the long bones. This relationship persists even after testosterone treatment.

While the presence of physical findings provides evidence of hypogonadism, their absence in an adult is less helpful because regression of secondary sexual characteristics, such as body hair and muscle mass, may not occur for years after the onset of hypogonadism. Consequently, men with symptoms of hypogonadism should be evaluated by appropriate laboratory tests even in the absence of physical findings.

Biochemical findings — As noted above, the biochemical features of hypogonadism in the adult male include the following:

The patient has primary hypogonadism if the serum testosterone concentration and/or the sperm count are below normal and the serum luteinizing hormone (LH) and/or follicle-stimulating hormone (FSH) concentrations are above normal.

The patient has secondary hypogonadism if the serum testosterone concentration and/or the sperm count are subnormal and the serum LH and/or FSH concentrations are normal or low.

DIAGNOSIS — The diagnosis is based upon the presence of signs and symptoms of male hypogonadism and unequivocally low serum total testosterone concentrations between 8 and 10 AM on at least two occasions (algorithm 1).

Candidates for testing — Population screening for male hypogonadism has not been shown to be cost effective and is not recommended [1]. Instead, we suggest case detection by measuring serum testosterone in situations in which the prevalence of hypogonadism is high, as suggested by the Endocrine Society guidelines [1]:

Diseases of the sellar region

Medications that affect testosterone production, such as high-dose glucocorticoids for a prolonged period and sustained-release opioids

Human immunodeficiency virus (HIV)-associated weight loss

End-stage kidney disease and maintenance hemodialysis

Moderate to severe chronic obstructive lung disease

Infertility

Osteoporosis or low-trauma fracture, especially in a young man

Type 2 diabetes mellitus

Men with acute or subacute illness should not be assessed for hypogonadism, as they will have a transient functional secondary hypogonadism.

Initial evaluation — The evaluation and diagnosis of male hypogonadism are usually straightforward. The clinician obtains clues to the possible presence of hypogonadism from the history and physical examination and confirms the diagnosis by appropriate laboratory testing (algorithm 1).

Initial laboratory testing is based upon measuring the products of the testes (testosterone and sperm) and the pituitary hormones that control their production (luteinizing hormone [LH] and follicle-stimulating hormone [FSH]). Testosterone is produced by the Leydig cells of the testes under stimulation of LH. Sperm are produced in the seminiferous tubules under stimulation principally by the high concentration of testosterone in the testes but also by FSH. Testosterone, in turn, inhibits both LH and FSH secretion, the latter via conversion to estradiol. FSH is also inhibited by inhibin, a product of the Sertoli cells of the seminiferous tubules.

Serum total testosterone — Measurement of the serum testosterone concentration is usually the most important single test in the evaluation of male hypogonadism because a low value usually indicates hypogonadism. Three aspects of testosterone measurement should be considered: what form (total or free), when during the day, and how often should serum testosterone be measured (algorithm 1)?

Measurement of the serum total (free plus protein-bound) testosterone concentration is usually an accurate reflection of testosterone secretion. The normal range in adult men in most laboratories is approximately 300 to 800 ng/dL.

Effect of abnormal SHBG — Measurement of the serum free testosterone concentration is worthwhile only when it is suspected that an abnormality in testosterone binding to sex hormone-binding globulin (SHBG) coexists with hypogonadism.

The two most common situations of abnormal testosterone binding are obesity, which decreases SHBG concentrations in proportion to the degree of obesity (figure 2) [2], and male aging, which increases SHBG slightly [3].

Obesity decreases the serum concentration of SHBG, thereby decreasing the serum total testosterone concentration, usually without lowering the free testosterone concentration (figure 2) [2,4]. The binding abnormality is proportional to the degree of obesity and is corrected by weight loss. However, severe obesity (body mass index [BMI] >40 kg/m2) may cause hypothalamic hypogonadism as well as the binding abnormality [5]. Measurement of the serum free testosterone in a laboratory capable of performing the equilibrium dialysis assay accurately will distinguish between a binding abnormality and hypogonadism in an obese male. (See 'Free testosterone' below.)

Although the serum total testosterone concentration falls slightly with increasing age, the serum free testosterone falls to a greater degree (figure 3). As a result, men who are 80 years old have values that are one-half to one-third of those in men who are 20 years old [3,6]. Studies suggest that this decrease has adverse consequences since increasing the testosterone levels of older men to those of young men improves their sexual function, walking, anemia, and bone density.

Causes of abnormal SHBG include the following:

Increased SHBG concentrations – Aging, hyperthyroidism, high estrogen concentrations, liver disease, HIV, antiseizure medications

Decreased SHBG concentrations – Moderate obesity, insulin resistance, type 2 diabetes, hypothyroidism, growth hormone excess, exogenous androgens/anabolic steroids, glucocorticoids, progestins, nephrotic syndrome

Free testosterone — If serum free testosterone concentration is measured, the following points should be kept in mind:

Serum free testosterone should be performed by equilibrium dialysis and only in those few laboratories that specialize in endocrine testing.

The free testosterone concentration, as calculated from the total testosterone, SHBG, and albumin concentrations, is also available, but there are many different equations for this calculation and they give vastly different results, some of which reflect the results obtained by equilibrium dialysis better than others [7]. Consequently, it is essential that the result be compared with the normal range for the laboratory that performed the assay.

Free testosterone measured by an analog method, which is the assay most commonly offered by hospital and commercial laboratories, does not correlate with the results of equilibrium dialysis. This test gives misleading information and should never be ordered.

The problem with the analog method was illustrated in a study in which sera from patients who had a variety of SHBG concentrations were assayed by each of the above methods [8]. The results using each of the assays correlated well with the results using each of the other methods, except for free testosterone by the analog method, in which the results were both systematically lower than in the other methods and varied as a function of SHBG.

When during the day should the serum testosterone concentration be measured? — Interpretation of serum testosterone measurements in men should take into consideration its diurnal fluctuation, which reaches a maximum at about 8 AM and a minimum (approximately 70 percent of the maximum) at about 8 PM (figure 4) [9]. It is easier to distinguish subnormal from normal when normal is higher, so the measurements should always be made in the morning, ideally between 8 to 10 AM. Food [10], especially glucose ingestion [11], also decreases the serum testosterone concentration, so the blood should also be drawn fasting.

How often should testosterone be measured? — The serum testosterone concentration fluctuates somewhat even early in the morning, although to a limited degree. If a single 8 to 10 AM value is well within the normal range, testosterone production can be assumed to be normal. If a single 8 to 10 AM value is low or borderline low or does not fit with the clinical findings, the measurement should be repeated once or twice before making the diagnosis of hypogonadism. If the results are equivocal, measurement of free testosterone can be considered [1]. (See "Testosterone treatment of male hypogonadism", section on 'Hypogonadal adult men'.)

LH and FSH — If the serum testosterone is below normal on two occasions, a serum luteinizing hormone (LH) concentration should be measured to distinguish primary from secondary hypogonadism (algorithm 1). Measuring basal serum concentrations of both LH and follicle-stimulating hormone (FSH) help to interpret subnormal values for serum testosterone and sperm count. However, a semen analysis is not part of the evaluation for all men presenting with hypogonadism, only those pursuing fertility or those with known infertility. The following patterns may be found:

If the serum testosterone concentration is subnormal, supranormal serum LH and FSH concentrations (normal range for both approximately 1 to 8 mIU/mL in most laboratories) indicate primary hypogonadism and values that are not supranormal indicate secondary hypogonadism. Clearly elevated gonadotropin values are indicative of primary hypogonadism even if the serum testosterone concentration is in the low-normal range. Age probably causes some degree of secondary hypogonadism, so an elevated LH due to primary hypogonadism may not be as high in older men as in younger men.

Some men with primary hypogonadism present with a subnormal sperm count, high serum FSH, but normal serum testosterone and LH concentrations. This pattern indicates seminiferous tubule damage, but normal testosterone production by the Leydig cells.

In secondary hypogonadism, measuring the serum LH response to exogenous gonadotropin-releasing hormone (GnRH) is not helpful in distinguishing pituitary from hypothalamic disease because a subnormal response occurs in both settings.

Semen analysis — In men being evaluated for infertility, analysis of semen, especially the number of sperm in an ejaculated specimen and their motility, is the best means of assessing sperm production and function in the postpubertal male. Normal men produce more than 15 million sperm/mL of ejaculate and more than 39 million sperm/total ejaculate [12]. In addition, normally, more than 40 percent of the sperm ejaculated are motile, more than 32 percent have rapid forward progression, and more than 4 percent have normal morphology (using "strict" Tygerberg methods) [12,13]. The role of the semen analysis in the evaluation of male infertility is reviewed in detail separately. (See "Approach to the male with infertility", section on 'Semen analysis'.)

A severely subnormal sperm count, eg, below five million sperm/ejaculate, can occur with either primary or secondary hypogonadism.

A mildly subnormal sperm count (eg, 39 million sperm/ejaculate, as defined by the World Health Organization [WHO]) associated with markedly abnormal sperm motility is much more likely to be associated with either a sperm function abnormality or primary hypogonadism than with secondary hypogonadism. (See "Approach to the male with infertility", section on 'Reference limits'.)

ADDITIONAL TESTING TO DETERMINE ETIOLOGY

Possible causes — Patients should also be asked about and examined for clues to possible causes of hypogonadism, including (table 2 and table 3):

Gynecomastia, small firm testes, and behavioral/learning abnormalities suggest Klinefelter syndrome. (See "Causes of primary hypogonadism in males", section on 'Klinefelter syndrome'.)

Chemotherapy (eg, alkylating agents such as cyclophosphamide), radiation therapy (to the pelvis or as part of total body protocols), excessive alcohol consumption, bilateral torsion, trauma, or a history of painful testicular swelling (as may occur with mumps orchitis) suggests primary testicular failure as a cause of infertility. (See "Effects of cytotoxic agents on gonadal function in adult men" and "Causes of male infertility".)

Anosmia or hyposmia suggests Kallmann syndrome. (See "Isolated gonadotropin-releasing hormone deficiency (idiopathic hypogonadotropic hypogonadism)".)

Peripheral vision abnormalities or pituitary target gland hormone deficiencies suggest a mass lesion in the pituitary gland or hypothalamus. (See "Causes, presentation, and evaluation of sellar masses".)

Medications that cause primary or secondary hypogonadism, such as ketoconazole or sustained-release opioid preparations, respectively. (See "Causes of primary hypogonadism in males", section on 'Acquired diseases' and "Causes of secondary hypogonadism in males", section on 'Acquired diseases'.)

Primary hypogonadism — There are certain settings in which other tests may be helpful (algorithm 1):

Karyotype — Determination of the peripheral leukocyte karyotype should be considered in a man who has primary hypogonadism unrelated to a known acquired etiology to determine if Klinefelter syndrome is the cause because of the nongonadal features of Klinefelter. (See "Causes of primary hypogonadism in males", section on 'Klinefelter syndrome'.)

Secondary hypogonadism

Pituitary function testing — Men who have acquired secondary hypogonadism should be evaluated for other pituitary hormonal deficiencies by measurement of the serum concentrations of cortisol at 8 AM and of thyroxine or free thyroxine. (See "Diagnostic testing for hypopituitarism".)

Men who have acquired secondary hypogonadism should also be considered for evaluation of possible causes by measuring the serum concentration of prolactin and iron saturation.

MRI — In men with secondary hypogonadism, magnetic resonance imaging (MRI) should always be performed if the patient has other pituitary hormonal abnormalities, a visual field abnormality, or other neurologic abnormalities. If there is no other evidence of pituitary or hypothalamic disease, finding a mass lesion on MRI is more likely the younger and healthier the patient and the lower the serum testosterone concentration.

In a man <40 years old, as an example, a confirmed testosterone value of <250 ng/dL would warrant an MRI, but in a man >60 years old, a value of <150 ng/dL would be necessary to warrant it. The rationale for the age differential is that the serum testosterone concentration decreases with increasing age, so that moderately low serum testosterone concentrations, eg, 200 to 300 ng/dL, are relatively common in men >65 years old and are usually not associated with sellar mass lesions (see "Approach to older males with low testosterone"). Illness, like age, might influence the decision.

Genetic testing — In men who have congenital isolated hypogonadotropic hypogonadism, genetic testing should be considered, especially if induction of fertility is planned. Genetic testing laboratories now offer batteries of tests for mutations known to cause this deficiency. (See "Isolated gonadotropin-releasing hormone deficiency (idiopathic hypogonadotropic hypogonadism)".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Male infertility or hypogonadism".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topic (see "Patient education: Late puberty (The Basics)" and "Patient education: Androgen replacement in men (The Basics)")

SUMMARY AND RECOMMENDATIONS

Definition – Hypogonadism in a male refers to a decrease in either or both of the two major functions of the testes: sperm production and testosterone production. These abnormalities may result from disease of the testes (primary hypogonadism) or disease of the pituitary or hypothalamus (secondary hypogonadism). (See 'Background' above.)

Signs and symptoms

Failure to undergo or complete puberty indicates deficient testosterone secretion. (See 'Time of onset' above.)

Symptoms that could indicate hypogonadism in a man are decreases in energy, libido, muscle mass, and body hair, as well as hot flashes, gynecomastia, and infertility. (See 'Clinical features' above.)

Candidates for testing – We suggest case detection by measuring serum testosterone when hypogonadism is suspected, such as in those with sexual symptoms, osteoporosis-associated fractures, human immunodeficiency virus (HIV)-associated weight loss, those taking sustained-release opioids or high-dose glucocorticoids for prolonged periods, and those who are incompletely virilized or have small testes on examination.

Men with acute or subacute illness should not be assessed for hypogonadism, as they will have a transient functional secondary hypogonadism. (See 'Candidates for testing' above.)

Evaluation

Serum total testosterone – To make the diagnosis of hypogonadism, we suggest measuring a morning serum total testosterone concentration between 8 and 10 AM on at least two days.

Serum free testosterone – Measurement of the serum free testosterone concentration is worthwhile only when it is suspected that an abnormality in testosterone binding to sex hormone-binding globulin (SHBG) coexists with hypogonadism. The two most common situations of abnormal testosterone binding are obesity, which decreases SHBG concentrations, and aging, which increases SHBG. (See 'Initial evaluation' above and 'Effect of abnormal SHBG' above.)

LH and FSH – If the total testosterone is subnormal, it should be repeated between 8 and 10 AM, and serum luteinizing hormone (LH) and follicle stimulating (FSH) concentrations should be measured to distinguish primary from secondary hypogonadism. (See 'LH and FSH' above.)

Semen analysis – A semen analysis is also part of the evaluation of hypogonadism if the patient is pursuing fertility or has been diagnosed with infertility. If subnormal, a serum FSH concentration is measured to distinguish primary from secondary hypogonadism. (See 'Semen analysis' above.)

Interpretation of results

Primary hypogonadism – The patient has primary hypogonadism if the serum testosterone concentration and/or the sperm count are consistently below normal and the serum LH and/or FSH concentrations are above normal. (See 'Primary hypogonadism' above.)

Secondary hypogonadism – The patient has secondary hypogonadism if the serum testosterone concentration and/or the sperm count are consistently subnormal and the serum LH and/or FSH concentrations are normal or reduced. (See 'Secondary hypogonadism' above.)

  1. Bhasin S, Cunningham GR, Hayes FJ, et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2010; 95:2536.
  2. Glass AR, Swerdloff RS, Bray GA, et al. Low serum testosterone and sex-hormone-binding-globulin in massively obese men. J Clin Endocrinol Metab 1977; 45:1211.
  3. Purifoy FE, Koopmans LH, Mayes DM. Age differences in serum androgen levels in normal adult males. Hum Biol 1981; 53:499.
  4. Mingrone G, Greco AV, Giancaterini A, et al. Sex hormone-binding globulin levels and cardiovascular risk factors in morbidly obese subjects before and after weight reduction induced by diet or malabsorptive surgery. Atherosclerosis 2002; 161:455.
  5. Giagulli VA, Kaufman JM, Vermeulen A. Pathogenesis of the decreased androgen levels in obese men. J Clin Endocrinol Metab 1994; 79:997.
  6. Deslypere JP, Vermeulen A. Leydig cell function in normal men: effect of age, life-style, residence, diet, and activity. J Clin Endocrinol Metab 1984; 59:955.
  7. Ly LP, Sartorius G, Hull L, et al. Accuracy of calculated free testosterone formulae in men. Clin Endocrinol (Oxf) 2010; 73:382.
  8. Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab 1999; 84:3666.
  9. Bremner WJ, Vitiello MV, Prinz PN. Loss of circadian rhythmicity in blood testosterone levels with aging in normal men. J Clin Endocrinol Metab 1983; 56:1278.
  10. Sartorius G, Spasevska S, Idan A, et al. Serum testosterone, dihydrotestosterone and estradiol concentrations in older men self-reporting very good health: the healthy man study. Clin Endocrinol (Oxf) 2012; 77:755.
  11. Caronia LM, Dwyer AA, Hayden D, et al. Abrupt decrease in serum testosterone levels after an oral glucose load in men: implications for screening for hypogonadism. Clin Endocrinol (Oxf) 2013; 78:291.
  12. Cooper TG, Noonan E, von Eckardstein S, et al. World Health Organization reference values for human semen characteristics. Hum Reprod Update 2010; 16:231.
  13. World Health Organization. WHO laboratory manual for the examination of human semen and sperm-cervical mucus interaction, 4th, Cambridge University Press, Cambridge, UK 2000.
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