help button home button Endocrine Society JCEM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mahmoud, A. M.
Right arrow Articles by Kaufman, J. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mahmoud, A. M.
Right arrow Articles by Kaufman, J. M.
The Journal of Clinical Endocrinology & Metabolism Vol. 88, No. 1 179-184
Copyright © 2003 by The Endocrine Society

Original Article

Testicular Volume in Relation to Hormonal Indices of Gonadal Function in Community-Dwelling Elderly Men

A. M. Mahmoud, S. Goemaere, Y. El-Garem, I. Van Pottelbergh, F. H. Comhaire and J. M. Kaufman

Department of Internal Medicine, Endocrinology Section (A.M.M., Y.E.-G., I.V.P., F.H.C., J.M.K.), and Unit for Osteoporosis and Metabolic Bone Diseases (S.G.), Ghent University Hospital, B-9000, Ghent, Belgium; and Andrology Department (Y.E.-G.), Faculty of Medicine, Alexandria University, Alexandria, Egypt 21544

Address all correspondence and requests for reprints to: Dr. Jean-Marc Kaufman, Ghent University Hospital, Department of Internal Medicine, Section Endocrinology, De Pintelaan 185 B-9000, Ghent, Belgium. E-mail: jean.kaufman{at}rug.ac.be.


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
Aging is accompanied by involutional changes in testicular function; limited data suggest a decrease in bilateral testicular volume (BTV). We studied BTV by ultrasonography in relation to serum gonadal hormones in 115 healthy elderly men (median age, 78 yr) and 42 young men (median age, 26.5 yr). Elderly men had a clearly smaller BTV (mean, 20.6 vs. 29.7 ml; P < 0.001), whereas serum inhibin B was slightly but significantly decreased (mean, 176.8 vs. 212.8 ng/liter; P = 0.04); lower values in the elderly were observed for bioavailable (Bio) testosterone (T), Bio 17ß-estradiol, inhibin B/FSH (mean, 18 vs. 58 ng/mU; P < 0.001), and T/LH ratios. In the elderly and the young, respectively, BTV was associated with inhibin B (r = 0.53, P < 0.001; r = 0.41, P < 0.01), FSH (r = -0.53, P < 0.001; r = -0.48, P < 0.01), and inhibin B/FSH ratio. Only in the old men was BTV significantly associated with LH (r = -0.32; P < 0.001), Bio T (r = 0.26; P < 0.01), and T/LH (r = 0.48; P < 0.001). In a multivariate analysis, FSH, inhibin B, and Bio T were independently associated with BTV in the elderly (R2 = 0.34). Receiver operating characteristics curve analysis indicated that BTV at a criterion value of 14.3 ml had a sensitivity of 46% and a specificity of 79% to predict low serum Bio T levels in the elderly. In conclusion, the moderately decreased BTV observed in elderly men, strongly associated with a decrease of the inhibin B/FSH ratio, is consistent with a reduced Sertoli cell mass, compensated by increased FSH stimulation resulting in only limited decrease of Sertoli cell function. Finding of a low testicular volume in elderly men can contribute to the diagnosis of hypogonadism, but this criterion has low sensitivity to detect decreased T production.


   Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
AGING IN HEALTHY men is associated with various changes in the hypothalamo-pituitary-testicular axis. This is manifested by a progressive, albeit variable, decline of Leydig cell function with an approximately 50% decrease of mean serum free [or bioavailable (Bio)] testosterone (T) levels in the population between ages 25 and 75 yr (1, 2, 3, 4). Underlying this decrease of T production are both primary testicular changes with reduced secretory response to gonadotropic stimulation (5) and alterations of the neuroendocrine regulation of Leydig cell function, with inadequate LH response to the prevailing state of relative hypoandrogenism (6, 7, 8).

Aging is also accompanied by an increase of FSH (9, 10), but limited available information indicates relatively well preserved spermatogenesis. A recent meta-analysis suggests that age is associated with some decline in semen volume, sperm motility, and sperm morphology but not sperm concentration (11). However, the available studies evaluated selected populations and included small numbers of men older than 60 yr of age (11). Besides the impracticability of obtaining semen samples from large numbers of elderly men, the use of semen analysis in epidemiological studies is hampered by technical problems (for review, see Refs.12 and13). Although Sertoli cell function and spermatogenic activity, as assessed indirectly through serum inhibin B levels, appear to be rather well maintained in ambulatory elderly men, aging is accompanied by a progressive marked decrease of the inhibin B/FSH ratio (14).

Although the age-related decline of testicular function has received a lot of attention, its impact on the well-being of elderly men remains ill defined, and the diagnostic criteria for hypogonadism in the elderly are controversial (15).

In this context, it is surprising that there is little compelling data on the age-related changes in testicular volume and virtually no information on the relationship between hormonal changes and testicular volume in aging men. Most available studies are inconclusive due to the small size and/or highly selective character of the considered sample of elderly men (16, 17, 18, 19, 20, 21, 22, 23). Moreover, these smaller studies yielded inconsistent results. In a larger necropsy study, Handelsman and Staraj (24) observed a decrease in testicular volume from the eighth decade on; in that study hormonal data were not obtained. A study by Stearns et al. (25) is the only larger study reporting on testicular volume and hormones in the elderly, but in their study, testicular volume in the elderly was compared with historical controls.

The aim of the present study was to assess testicular volume in a sizable group of elderly men over 70 yr of age in comparison with young men and in relation to hormonal indices of both Sertoli cell and Leydig cell function. Indeed, it is presently unknown how the age-related changes in testicular function, with mixed testicular and central pathogenesis, are reflected in changes in testicular size and in how far the relationship between the hormone levels and testicular volume might differ between the young and the elderly. The latter also has implications for the use of testicular volume in the clinical evaluation of elderly men.


   Subjects and Methods
Top
 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
Subjects

The elderly ambulatory men in this study (n = 168) have been recruited from the population register of a semirural community of 20,000 inhabitants near the Ghent University Hospital (Ghent, Belgium) and constitute a subgroup of a study population included in an ongoing longitudinal observational study initiated in 1996 on the relationship between androgen status and bone mineral density. The only initial selection criteria were age between 70 and 85 yr and willingness to participate. The data presented here have been obtained in a subgroup of the population at the occasion of the fifth yearly investigation performed in 2000. Included in the present study are also younger male reference subjects (18–40 yr; n = 71) consisting of volunteering students and hospital staff members. All men included in the study were Caucasians. All participants gave a written informed consent for participation in this study approved by the Ethical Committee of the Ghent University Hospital.

Data were analyzed after the exclusion of subjects (29 young men and 53 elderly men) with a history or physical finding indicative of gonadal abnormality including varicocele, cryptorchidism, testicular torsion, and orchitis, or on the basis of active debilitating diseases or the use of any of the following medications: androgens, antiandrogens, insulin and oral antidiabetic agents, antiepileptic drugs, dopaminergic drugs and neuroleptics, systemic glucocorticoids, and cimetidine. Debilitating diseases leading to exclusion from the study were osteoporosis requiring treatment, hyperthyroidism, adrenal insufficiency, malignancy, inflammatory rheumatic disease, elevated serum calcium (>2.65 mmol/liter), elevated fasting glucose (>8.33 mmol/liter), elevated serum creatinine (>177 µmol/liter), recent myocardial infarction, cerebrovascular accidents, or decompensated chronic obstructive pulmonary disease.

Common diseases in our study population that have not been reason for exclusion were atherosclerosis, treated hypertension, benign prostatic hypertrophy, osteoarthrosis, diabetes controlled with only diet, and compensated chronic obstructive pulmonary disease not requiring systemic steroid therapy.

Data from baseline examinations in 1996 of larger subgroups of the same elderly study population have been the subject of separate reports on not directly related issues as well as a report on inhibin B serum levels (14).

History taking, physical examination, and testicular volume measurement

History taking and physical examination were performed according to the recommendations of the World Health Organization (26). Testicular dimensions were measured using ultrasonography with a 7.5-MHz probe (Ultramark 6, Advanced Technology Laboratories, Bothell, WA). This method has been previously characterized as objective, accurate, and reproducible (27). The testicular volume was calculated using the following formula: V = {pi}/6 x L x D2, where V = testis volume, L = maximal length of the testis, and D = maximal diameter of the testis (27). The total testicular volume was calculated as the sum of the right and left testis volumes.

Hormone assays

Venous blood was obtained between 0800 and 1000 h, after an overnight fast. Serum was stored at -80 C until assay. Serum samples of elderly men and controls were proportionally represented in each hormone assay run.

Commercial kits for RIA were used to determine the serum concentrations of T (Medgenics Diagnostics, Fleurus, Belgium) and estradiol (E2; INCSTAR Corp., Stillwater, MN); commercial kits for immunoradiometric assays were used for determinations of serum SHBG (Orion Diagnostica, Espoo, Finland), LH, and FSH (Medgenics Diagnostics). Intra- and interassay coefficients of variation for all of these assays were less than 10 and 15%, respectively.

Serum Bio T and Bio E2 were calculated from the total serum hormone concentrations, serum SHBG, and serum albumin, using an equation derived from the mass action law (28).

Serum inhibin B was determined in duplicate using a specific (29) double-antibody, enzyme-linked immunoassay (Inhibin-B, dimer assay kit ultra-sensitive, Serotec, Oxford, UK). Intra- and interassay coefficients of variation were 6% and 9%, respectively.

Statistics

Some variables in the analysis turned out to be skewed. Their distributions were therefore characterized by the median and interquartile range. The t test was used, after transformations to obtain normal distributions when necessary, to test differences between the groups studied. Otherwise, the Mann-Whitney U test was used. Spearman rank correlations were calculated for studying univariate associations. To study the simultaneous effects of various variables on serum inhibin levels and total testicular volume, multiple linear regression was used. An a priori 5% level was used to indicate statistical significance. The receiver operating characteristics (ROC) curve was used to determine within the group of elderly men the performance of the total testicular volume in differentiating between men with low (positive group) or normal Bio T levels (negative group), using the mean -2.5 SD of Bio T level in the young control population as the lower limit of normality (4.9 nmol/liter). Statistical analyses were performed using SPSS software (SPSS for Windows, release 10.0.5, SPSS, Inc., Chicago, IL) and Medcalc software for ROC curve analysis (Medcalc for Windows, Version 6.16; Medcalc, Mariakerke, Belgium).


   Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
The findings for the considered variables in the ambulatory elderly men compared with the reference group of young men are summarized in Table 1Go. The mean testicular volume in men over 75 yr is 31% smaller than in the 18- to 40-yr-old men. This difference in testicular volume is accompanied by significantly higher mean serum levels of gonadotropins and lower serum Bio T. Serum inhibin B is slightly but significantly lower in the elderly by 17%. Figure 1AGo illustrates the shift in distribution toward lower values for total testicular volume in the elderly compared with young men, with more similar distribution patterns for serum inhibin B between age groups (Fig. 1BGo). The slight decrease of mean serum inhibin B in the elderly is largely due to 12% of the elderly men presenting with very low serum inhibin B (<50 ng/liter); in fact, the median inhibin B serum level in the elderly is only 10% lower than in the young control population, i.e. 174 vs. 194 ng/liter. Both the inhibin B/FSH and T/LH ratios are markedly lower in the elderly compared with the younger men. The elderly men with very low inhibin B (<50 ng/liter) were not significantly older than the rest of the elderly men (median age, 79 vs. 78 yr), but they had a significantly smaller total testicular volume (mean ± SD, 8.3 ± 5.7 vs. 22.3 ± 10.3 ml; P < 0.0001), lower Bio T (4.1 ± 1.4 vs. 5.4 ± 1.5 nmol/liter), and higher LH and FSH levels (data not shown), indicating marked primary testicular failure.


View this table:
[in this window]
[in a new window]
  		Table 1. Serum inhibin B, FSH, sex steroid levels, and total testicular volume in the age groups of selected men

 


View larger version (24K):
[in this window]
[in a new window]
  		Figure 1. Frequency distribution of total testicular volume (A) and inhibin B (B) in 115 elderly men (median age, 78 yr) and 42 young controls (median age, 26.5 yr).

 
ROC curve analysis indicated that in the elderly, total testicular volume at a criterion value of 14.3 ml or less had a rather low accuracy in differentiating elderly men with low Bio T (i.e. >2.5 SD below the mean for young men or <4.9 nmol/liter) from those with normal Bio T levels in serum, with an area under the curve of 0.611 [95% confidence interval (CI), 0.514–0.702], a sensitivity of 45.8% (95% CI, 31.4–60.8) a specificity of 79.4% (95% CI, 67.3–88.5), a positive likelihood ratio of 2.22, and a negative likelihood ratio of 0.68.

The associations between the variables studied within the groups of young and elderly men, respectively, are shown on Table 2Go. In both the young and the elderly, testicular volume was strongly associated positively with serum inhibin B and negatively with serum FSH, and thus also strongly positively associated to the inhibin B/FSH ratio. In the elderly but not in the young, testicular volume was also significantly associated positively with serum Bio T, negatively with serum LH, and positively with the T/LH ratio. Negative correlations between age and both Bio T and Bio E2, and a moderately positive association of age with serum inhibin B were observed in the young but not in the elderly. In both groups, serum inhibin B is strongly negatively correlated to FSH.


View this table:
[in this window]
[in a new window]
  		Table 2. Correlations between studied parameters in the young and elderly men

 
When fitting a multiple regression model for total testicular volume in the young group, which included multiple variables (Table 3Go), serum FSH is found to be the only independent determinant, with a rather low coefficient of determination (adjusted R2 = 0.16; P = 0.006). In the elderly (Table 4Go), FSH, inhibin B, and Bio T are selected as independent variables (adjusted R2 = 0.34; P < 0.001).


View this table:
[in this window]
[in a new window]
  		Table 3. Linear stepwise regression for the total testicular volume in young men (adjusted R2 = 0.156)

 

View this table:
[in this window]
[in a new window]
  		Table 4. Linear stepwise regression for the total testicular volume in old men (adjusted R2 = 0.342)

 
In a multiple regression model toward serum inhibin B that includes FSH, LH, total testicular volume, and Bio T, the determinants found to contribute independently in the group of young men are FSH and Bio T (adjusted R2 = 0.32; P < 0.001), whereas in the elderly, FSH, LH, and total testicular volume are selected as independent variables (adjusted R2 = 0.49; P < 0.001).


   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
The present study of testicular volume in relation to hormonal indices of gonadal function in a sizable group of healthy men in their eighth and ninth decades of life further refines our insight into the changes in testicular function in healthy old men. This study is, to the best of our knowledge, the first to analyze in detail the relationship between testicular volume, measured by ultrasonography, and hormonal indices of gonadal function in young and elderly men.

Testicular volume was found to be significantly smaller in the elderly compared with the young control group, which is in agreement with previous studies (18, 20, 21, 24). One study involving a small number of healthy men who had fathered children did not demonstrate such a decline (23). In the latter study, the elderly male population was about 10 yr younger than our group of elderly men, and the selection of men was based on proven fertility and may, therefore, not be representative of the general population. In a necropsy study, Handelsman and Staraj (24) observed that, in healthy men, age demonstrates a negative effect on testicular volume only from the eighth decade of life on. Most studies reporting on the effect of age on sperm parameters included relatively younger men compared with our elderly study population. Although these studies indicate no change in sperm concentration in men above 50 yr of age, a decrease of 3–22% in semen volume is reported, indicating at least some decline in the total sperm count (11).

Whereas testicular volume was clearly smaller in our elderly study population, serum inhibin B levels were less affected by aging, which confirms our previous finding on serum inhibin B obtained at baseline (4 yr earlier) in essentially the same elderly population (14). However, this limited decrease in inhibin B serum levels is accompanied by an almost 2-fold elevation of serum FSH levels, resulting in a marked decrease in the inhibin B/FSH ratio. The latter findings together with the reduced testicular volume are consistent with the concept that in elderly men Sertoli cell mass is reduced (30), with compensatory increase of FSH stimulation allowing for global Sertoli cell function (and spermatogenesis) to be relatively preserved. The subgroup of elderly men with very low inhibin B serum levels (<50 ng/liter) had a small testicular volume, lower Bio T, and higher LH and FSH, indicating marked primary testicular failure. This might reflect the existence of testicular pathology distinct from the normal aging, even though subjects with detectable causes of testicular failure were excluded. It is also possible that these changes represent an extreme of the spectrum of age-related alterations in testicular function.

Our findings show that the strong association between total testicular volume and serum inhibin B levels that has been reported for young men (13, 31, 32, 33, 34) also holds true in the oldest old. Interestingly, total testicular volume is similarly strongly correlated to serum FSH, serum inhibin B, and the inhibin B/FSH ratio in the elderly and in the younger reference group; whereas associations between testicular volume and Bio T, LH, and the T/LH ratio were clearly more prominent in the elderly compared with the young. The latter observation seems consistent with the view that age-related testicular changes affect both the Leydig cell and Sertoli cell function with, however, in the elderly, preservation of the neuroendocrine regulation of Sertoli cell function by FSH that is operational in young men, whereas in the case of Leydig cell function, involutional testicular changes are also accompanied by age-related alterations in the neuroendocrine regulation of LH secretion (6, 14).

The similar correlations between the total testicular volume and both FSH and inhibin B suggest that inhibin B does not provide additional information on Sertoli cell function. Nevertheless, multivariate analyses show that in the elderly, but not in the young, serum inhibin B is associated with testicular volume independently from serum FSH. This, in turn, indicates that in the elderly the decline of Sertoli cell mass is not fully compensated by increased FSH stimulation, or is not compensated in all subjects as suggested by the occurrence of a minority (i.e. 12%) of elderly men with very low serum inhibin B.

As to the predictive power of testicular volume for Bio T production in the elderly, ROC curve analysis of our data indicated that the total testicular volume had low sensitivity but reasonable specificity in differentiating between men with low or normal Bio T serum levels. In other words, the probability of an elderly man having a total testicular volume of 14.3 ml or less when his Bio T level in serum is decreased is only 46%, whereas there is an 80% probability of having a total testicular volume larger than 14.3 ml when Bio T level in serum is normal.

In conclusion, the strong correlation between testicular volume and serum inhibin B is maintained until old age in healthy men. An age-related moderate decrease of testicular volume reflects a decrease of Sertoli cell mass, global Sertoli cell function being largely, but not fully, preserved at the cost of increased pituitary FSH stimulation. Finding of a low testicular volume in elderly men can contribute to the diagnosis of hypogonadism, but this criterion has low sensitivity to detect decreased T production.


   Acknowledgments
 
We are indebted to Sabrina Stuyvaert and Inge Bocquaert for their expert technical assistance and to the team of the Unit for Osteoporosis and Metabolic Bone Diseases of the Ghent University Hospital for their invaluable assistance in the practical realization of this study.


   Footnotes
 
This work was supported by Grant G0058-97 of the Fonds voor Wetenschappelijk Onderzoek Vlaanderen. I.V.P. is a research fellow for the Fund for Scientific Research (Fonds Voor Wetenschappelijk Onderzoek Vlaanderen).

Parts of this work were presented at the 84th Annual Meeting of The Endocrine Society, San Francisco, CA, 2002 (Abstract P3-310) and the Third World Congress on the Aging Male, Berlin, Germany, 2002.

Abbreviations: Bio, Bioavailable; CI, confidence interval; E2, 17ß- estradiol; ROC, receiver operating characteristics; T, testosterone.

Received March 14, 2002.

Accepted October 10, 2002.


   References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

  1. Ferrini RL, Barrett-Connor E 1998 Sex hormones and age: a cross-sectional study of testosterone and estradiol and their bioavailable fractions in community-dwelling men. Am J Epidemiol 147:750–754[Abstract/Free Full Text]
  2. Morley JE, Kaiser FE, Perry HM, Patrick P, Morley PM, Stauber PM, Vellas B, Baumgartner RN, Garry PJ 1997 Longitudinal changes in testosterone, luteinizing hormone, and follicle-stimulating hormone in healthy older men. Metabolism 46:410–413[CrossRef][Medline]
  3. Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR 2001 Longitudinal effects of aging on serum total and free testosterone levels in healthy men. J Clin Endocrinol Metab 86:724–731[Abstract/Free Full Text]
  4. Vermeulen A 1991 Androgens in the aging male. J Clin Endocrinol Metab 73:221–224[Abstract/Free Full Text]
  5. Mulligan T, Iranmanesh A, Veldhuis JD 2001 Pulsatile iv infusion of recombinant human LH in leuprolide-suppressed men unmasks impoverished Leydig-cell secretory responsiveness to midphysiological LH drive in the aging male. J Clin Endocrinol Metab 86:5547–5553[Abstract/Free Full Text]
  6. Vermeulen A, Kaufman JM 1992 Role of the hypothalamo-pituitary function in the hypoandrogenism of healthy aging. J Clin Endocrinol Metab 75:704–706[CrossRef][Medline]
  7. Kaufman JM, Vermeulen A 1997 Declining gonadal function in elderly men. Baillieres Clin Endocrinol Metab 11:289–309[CrossRef][Medline]
  8. Veldhuis JD, Urban RJ, Dufau ML 1992 Evidence that androgen negative feedback regulates hypothalamic gonadotropin-releasing hormone impulse strength and the burst-like secretion of biologically active luteinizing hormone in men. J Clin Endocrinol Metab 74:1227–1235[Abstract]
  9. Matzkin H, Braf Z, Nava D 1991 Does age influence the bioactivity of follicle-stimulating hormone in men? Age Ageing 20:199–205[Abstract/Free Full Text]
  10. Urban RJ, Dahl KD, Lippert MC, Veldhuis JD 1992 Modulation of immunoradiometric and bioactive follicle stimulating hormone secretion and clearance in young and elderly men during treatment with tamoxifen or flutamide. J Androl 13:579–586[Abstract/Free Full Text]
  11. Kidd SA, Eskenazi B, Wyrobek AJ 2001 Effects of male age on semen quality and fertility: a review of the literature. Fertil Steril 75:237–248[CrossRef][Medline]
  12. Mahmoud AM, Depoorter B, Piens N, Comhaire FH 1997 The performance of 10 different methods for the estimation of sperm concentration. Fertil Steril 68:340–345[CrossRef][Medline]
  13. Mahmoud AM, Comhaire FH, Depuydt CE 1998 The clinical and biologic significance of serum inhibins in subfertile men. Reprod Toxicol 12:591–599[CrossRef][Medline]
  14. Mahmoud AM, Goemaere S, De Bacquer D, Comhaire FH, Kaufman JM 2000 Serum inhibin B levels in community-dwelling elderly men. Clin Endocrinol (Oxf) 53:141–147[CrossRef][Medline]
  15. Vermeulen A 2001 Androgen replacement therapy in the aging male–a critical evaluation. J Clin Endocrinol Metab 86:2380–2390[Free Full Text]
  16. Johnson L, Petty CS, Neaves WB 1984 Influence of age on sperm production and testicular weights in men. J Reprod Fertil 70:211–218[Abstract/Free Full Text]
  17. Johnson L, Petty CS, Neaves WB 1986 Age-related variation in seminiferous tubules in men. A stereologic evaluation. J Androl 7:316–322[Abstract/Free Full Text]
  18. Johnson L, Abdo JG, Petty CS, Neaves WB 1988 Effect of age on the composition of seminiferous tubular boundary tissue and on the volume of each component in humans. Fertil Steril 49:1045–1051[Medline]
  19. Kothari LK, Gupta AS 1974 Effect of ageing on the volume, structure and total Leydig cell content of the human testis. Int J Fertil 19:140–146[Medline]
  20. Neaves WB, Johnson L, Porter JC, Parker CRJ, Petty CS 1984 Leydig cell numbers, daily sperm production, and serum gonadotropin levels in aging men. J Clin Endocrinol Metab 59:756–763[Abstract/Free Full Text]
  21. Paniagua R, Martin A, Nistal M, Amat P 1987 Testicular involution in elderly men: comparison of histologic quantitative studies with hormone patterns. Fertil Steril 47:671–679[Medline]
  22. Rolf C, Behre HM, Nieschlag E 1996 Reproductive parameters of older compared to younger men of infertile couples. Int J Androl 19:135–142[Medline]
  23. Nieschlag E, Lammers U, Freischem CW, Langer K, Wickings EJ 1982 Reproductive functions in young fathers and grandfathers. J Clin Endocrinol Metab 55:676–681[Abstract/Free Full Text]
  24. Handelsman DJ, Staraj S 1985 Testicular size: the effects of aging, malnutrition, and illness. J Androl 6:144–151[Abstract/Free Full Text]
  25. Stearns EL, MacDonnell JA, Kaufman BJ, Padua R, Lucman TS, Winter JS, Faiman C 1974 Declining testicular function with age. Hormonal and clinical correlates. Am J Med 57:761–766[CrossRef][Medline]
  26. Rowe PJ, Comhaire FH, Hargreave TB, Mahmoud AMA 2000 WHO manual for the standardized investigation, diagnosis and management of the infertile male, 1st Ed. Cambridge: Cambridge University Press
  27. Behre HM, Nashan D, Nieschlag E 1989 Objective measurement of testicular volume by ultrasonography: evaluation of the technique and comparison with orchidometer estimates. Int J Androl 12:395–403[Medline]
  28. Vermeulen A, Verdonck L, Kaufman JM 1999 A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab 84:3666–3672[Abstract/Free Full Text]
  29. Groome NP, Illingworth PJ, O’Brien M, Pai R, Rodger FE, Mather JP, McNeilly AS 1996 Measurement of dimeric inhibin B throughout the human menstrual cycle. J Clin Endocrinol Metab 81:1401–1405[Abstract]
  30. Johnson L, Zane RS, Petty CS, Neaves WB 1984 Quantification of the human Sertoli cell population: its distribution, relation to germ cell numbers, and age-related decline. Biol Reprod 31:785–795[Abstract]
  31. Cicognani A, Cacciari E, Pasini A, Burnelli R, De Iasio R, Pirazzoli P, Paolucci G 2000 Low serum inhibin B levels as a marker of testicular damage after treatment for a childhood malignancy. Eur J Pediatr 159:103–107[CrossRef][Medline]
  32. Lahteenmaki PM, Toppari J, Ruokonen A, Laitinen P, Salmi TT 1999 Low serum inhibin B concentrations in male survivors of childhood malignancy. Eur J Cancer 35:612–619
  33. Pierik FH, Vreeburg JT, Stijnen T, De Jong FH, Weber RF 1998 Serum inhibin B as a marker of spermatogenesis. J Clin Endocrinol Metab 83:3110–3114[Abstract/Free Full Text]
  34. Bohring C, Krause W 1999 Serum levels of inhibin B in men with different causes of spermatogenic failure. Andrologia 31:137–141[CrossRef][Medline]



This article has been cited by other articles:


Home page
 Eur J EndocrinolHome page
V. Bogaert, G. Vanbillemont, Y. Taes, D. De Bacquer, E. Deschepper, K. Van Steen, and J.-M. Kaufman
Small effect of the androgen receptor gene GGN repeat polymorphism on serum testosterone levels in healthy men
Eur. J. Endocrinol., July 1, 2009; 161(1): 171 - 177.
[Abstract] [Full Text] [PDF]

Home page
 Eur J EndocrinolHome page
B Lapauw, S Goemaere, H Zmierczak, I Van Pottelbergh, A Mahmoud, Y Taes, D De Bacquer, S Vansteelandt, and J M Kaufman
The decline of serum testosterone levels in community-dwelling men over 70 years of age: descriptive data and predictors of longitudinal changes
Eur. J. Endocrinol., October 1, 2008; 159(4): 459 - 468.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
T. Scalvini, P. R. Martini, A. Gambera, R. Tardanico, L. Biasi, F. Scolari, G. Gregorini, and E. Agabiti Rosei
Spermatogenic and Steroidogenic Impairment of the Testicle Characterizes the Hereditary Leucine-75-Proline Apolipoprotein A-I Amyloidosis
J. Clin. Endocrinol. Metab., May 1, 2008; 93(5): 1850 - 1853.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Chem.Home page
F. Giton, S. Urien, C. Born, J. Tichet, J. Guechot, J. Callebert, F. Bronsard, J. P. Raynaud, and J. Fiet
Determination of Bioavailable Testosterone [Non Sex Hormone Binding Globulin (SHBG)-Bound Testosterone] in a Population of Healthy French Men: Influence of Androstenediol on Testosterone Binding to SHBG
Clin. Chem., December 1, 2007; 53(12): 2160 - 2168.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
J. M. Kaufman and A. Vermeulen
The Decline of Androgen Levels in Elderly Men and Its Clinical and Therapeutic Implications
Endocr. Rev., October 1, 2005; 26(6): 833 - 876.
[Abstract] [Full Text] [PDF]

Home page
 Hum Reprod UpdateHome page
B. Kuhnert and E. Nieschlag
Reproductive functions of the ageing male
Hum. Reprod. Update, July 1, 2004; 10(4): 327 - 339.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
R. Luboshitzky, Z. Shen-Orr, and P. Herer
Middle-Aged Men Secrete Less Testosterone at Night Than Young Healthy Men
J. Clin. Endocrinol. Metab., July 1, 2003; 88(7): 3160 - 3166.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mahmoud, A. M.
Right arrow Articles by Kaufman, J. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mahmoud, A. M.
Right arrow Articles by Kaufman, J. M.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals