Male hypogonadism : an update on diagnosis and treatment.

Male hypogonadism is one of the most common endocrinologic syndromes. The diagnosis is based on clinical signs and symptoms plus laboratory confirmation via the measurement of low morning testosterone levels on two different occasions. Serum luteinizing hormone and follicle-stimulating hormone levels distinguish between primary (hypergonadotropic) and secondary (hypogonadotropic) hypogonadism. Hypogonadism associated with aging (andropause) may present a mixed picture, with low testosterone levels and low to low-normal gonadotropin levels. Androgen replacement therapy in hypogonadal men has many potential benefits: improved sexual function, an enhanced sense of well-being, increased lean body mass, decreased body fat, and increased bone density. However, it also carries potential risks, including the possibility of stimulating the growth of an occult prostate cancer. The benefits of androgen therapy outweigh the risks in men with classic hypogonadism. However, for men with mild hypogonadism or andropause, the balance between benefits and risks is not always clear. Unfortunately, studies to date have included too small a number of patients and have been too short in duration to provide meaningful data on the long-term risks versus the benefits of androgen replacement therapy in these populations. Several products are currently marketed for the treatment of male hypogonadism. Weekly-to-biweekly injections of testosterone cypionate (cipionate) or testosterone enanthate (enantate) are widely used, as they are economical and generally well tolerated. However, once-daily transdermal therapies have become increasingly popular and now include both patch and gel systems. Intramuscular injection of testosterone undecanoate is an attractive new therapy that can be administered quarterly. To confirm an adequate replacement dosage, assessment of clinical responses and measurement of serum testosterone levels generally suffice. For selected men, serial measurement of bone mineral density during androgen therapy might be helpful to confirm end-organ effects. For men aged >50 years, we advocate measurement of hematocrit for detection of polycythemia and a digital rectal examination with a serum prostate-specific antigen level measurement for prostate cancer screening during the first few months of androgen therapy. Subsequently, a hematocrit should be obtained yearly or after changes in therapy, and annual prostate cancer screening can be offered to the patient after a discussion of its risks and benefits.

[1]  R. Casaburi,et al.  Dose-dependent effects of testosterone on sexual function, mood, and visuospatial cognition in older men. , 2005, The Journal of clinical endocrinology and metabolism.

[2]  W. Bremner,et al.  Oral testosterone in oil plus dutasteride in men: a pharmacokinetic study. , 2005, The Journal of clinical endocrinology and metabolism.

[3]  A. Matsumoto,et al.  Exogenous testosterone (T) alone or with finasteride increases physical performance, grip strength, and lean body mass in older men with low serum T. , 2005, The Journal of clinical endocrinology and metabolism.

[4]  Duane D. Miller,et al.  Comparison of the pharmacological effects of a novel selective androgen receptor modulator, the 5alpha-reductase inhibitor finasteride, and the antiandrogen hydroxyflutamide in intact rats: new approach for benign prostate hyperplasia. , 2004, Endocrinology.

[5]  A. Araujo,et al.  Prevalence and incidence of androgen deficiency in middle-aged and older men: estimates from the Massachusetts Male Aging Study. , 2004, The Journal of clinical endocrinology and metabolism.

[6]  U. Jonas,et al.  Review article Testosterone therapy in the ageing male: what about the prostate? , 2004, Andrologia.

[7]  T. Gasser,et al.  Is there a clinical relevance of partial androgen deficiency of the aging male? , 2004, The Journal of urology.

[8]  A. Dobs,et al.  New testosterone buccal system (Striant) delivers physiological testosterone levels: pharmacokinetics study in hypogonadal men. , 2004, The Journal of clinical endocrinology and metabolism.

[9]  R. Jones,et al.  Testosterone replacement in hypogonadal men with angina improves ischaemic threshold and quality of life , 2004, Heart.

[10]  Ali Iranmanesh,et al.  Long-term testosterone gel (AndroGel) treatment maintains beneficial effects on sexual function and mood, lean and fat mass, and bone mineral density in hypogonadal men. , 2004, The Journal of clinical endocrinology and metabolism.

[11]  M. Korbonits,et al.  A comparison of a novel testosterone bioadhesive buccal system, striant, with a testosterone adhesive patch in hypogonadal males. , 2004, The Journal of clinical endocrinology and metabolism.

[12]  C. Christiansen,et al.  The aging male: testosterone deficiency and testosterone replacement. An up-date. , 2004, Atherosclerosis.

[13]  David Handelsman,et al.  Testosterone release rate and duration of action of testosterone pellet implants , 2004, Clinical Endocrinology.

[14]  A. Hoffman,et al.  Transdermal testosterone gel: pharmacokinetics, efficacy of dosing and application site in hypogonadal men , 2004, BJU international.

[15]  A. Dobs,et al.  Short-term pharmacokinetic comparison of a novel testosterone buccal system and a testosterone gel in testosterone deficient men , 2004, Current medical research and opinion.

[16]  Christina Wang,et al.  Measurement of total serum testosterone in adult men: comparison of current laboratory methods versus liquid chromatography-tandem mass spectrometry. , 2004, The Journal of clinical endocrinology and metabolism.

[17]  N. Watts,et al.  Exogenous testosterone or testosterone with finasteride increases bone mineral density in older men with low serum testosterone. , 2004, The Journal of clinical endocrinology and metabolism.

[18]  A. Morgentaler,et al.  Risks of testosterone-replacement therapy and recommendations for monitoring. , 2004, The New England journal of medicine.

[19]  P. Stattin,et al.  High levels of circulating testosterone are not associated with increased prostate cancer risk: A pooled prospective study , 2004, International journal of cancer.

[20]  Ruth Etzioni,et al.  Endogenous sex hormones and prostate cancer risk: a case-control study nested within the Carotene and Retinol Efficacy Trial. , 2003, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[21]  B. Anawalt,et al.  Male hypogonadism in the primary care clinic. , 2003, Primary care.

[22]  S. Bhasin Testosterone supplementation for aging-associated sarcopenia. , 2003, The journals of gerontology. Series A, Biological sciences and medical sciences.

[23]  P. Delmas,et al.  Increased risk of falls and increased bone resorption in elderly men with partial androgen deficiency: the MINOS study. , 2003, The Journal of clinical endocrinology and metabolism.

[24]  W. Schill,et al.  A new oral testosterone undecanoate formulation , 2003, World Journal of Urology.

[25]  B. Lunenfeld Androgen therapy in the aging male , 2003, World Journal of Urology.

[26]  G. Scriba,et al.  Oral testosterone-triglyceride conjugate in rabbits: single-dose pharmacokinetics and comparison with oral testosterone undecanoate. , 2003, Journal of andrology.

[27]  H. Perry,et al.  Andropause: an old concept in new clothing. , 2003, Clinics in geriatric medicine.

[28]  Michael M Lieber,et al.  The influence of finasteride on the development of prostate cancer. , 2003, The New England journal of medicine.

[29]  Matthew T. Haren,et al.  Oral testosterone supplementation increases muscle and decreases fat mass in healthy elderly males with low-normal gonadal status. , 2003, The journals of gerontology. Series A, Biological sciences and medical sciences.

[30]  C. Reiners,et al.  Osteoporosis in Male Hypogonadism: Responses to Androgen Substitution Differ among Men with Primary and Secondary Hypogonadism , 2003, Hormone Research in Paediatrics.

[31]  T. Smith,et al.  AA2500 testosterone gel normalizes androgen levels in aging males with improvements in body composition and sexual function. , 2003, The Journal of clinical endocrinology and metabolism.

[32]  Richard A. Anderson,et al.  Evidence for tissue selectivity of the synthetic androgen 7 alpha-methyl-19-nortestosterone in hypogonadal men. , 2003, The Journal of clinical endocrinology and metabolism.

[33]  W. Fraser,et al.  Diurnal rhythms of serum total, free and bioavailable testosterone and of SHBG in middle‐aged men compared with those in young men , 2003, Clinical endocrinology.

[34]  S. Bhasin,et al.  Managing the risks of prostate disease during testosterone replacement therapy in older men: recommendations for a standardized monitoring plan. , 2003, Journal of andrology.

[35]  T. Smith,et al.  Evaluation of the pharmacokinetic profiles of the new testosterone topical gel formulation, Testim™, compared to AndroGel® , 2003, Biopharmaceutics & drug disposition.

[36]  A. von Eckardstein,et al.  Androgens and coronary artery disease. , 2003, Endocrine reviews.

[37]  Duane D. Miller,et al.  Pharmacodynamics of Selective Androgen Receptor Modulators , 2003, Journal of Pharmacology and Experimental Therapeutics.

[38]  J. Chung,et al.  Oral testosterone undecanoate (Andriol®) supplement therapy improves the quality of life for men with testosterone deficiency , 2003, The aging male : the official journal of the International Society for the Study of the Aging Male.

[39]  J. Kaufman The effect of androgen supplementation therapy on the prostate , 2003, The aging male : the official journal of the International Society for the Study of the Aging Male.

[40]  A. Matsumoto,et al.  Testosterone Supplementation Therapy for Older Men: Potential Benefits and Risks , 2003, Journal of the American Geriatrics Society.

[41]  T. McNicholas,et al.  A novel testosterone gel formulation normalizes androgen levels in hypogonadal men, with improvements in body composition and sexual function , 2003, BJU international.

[42]  J. Patrie,et al.  Single and combined effects of growth hormone and testosterone administration on measures of body composition, physical performance, mood, sexual function, bone turnover, and muscle gene expression in healthy older men. , 2002, The Journal of clinical endocrinology and metabolism.

[43]  A. Morales,et al.  Androgen deficiency in the aging male: when, who, and how to investigate and treat. , 2002, The Urologic clinics of North America.

[44]  S. Petak,et al.  American Association of Clinical Endocrinologists Medical Guidelines for clinical practice for the evaluation and treatment of hypogonadism in adult male patients--2002 update. , 2002, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[45]  E. Nieschlag,et al.  Interpersonal testosterone transfer after topical application of a newly developed testosterone gel preparation , 2002, Clinical endocrinology.

[46]  H. Perry,et al.  Evaluation of assays available to measure free testosterone. , 2002, Metabolism: clinical and experimental.

[47]  D. Kadmon,et al.  The Long-Term Effect Of Specific Type II 5α-Reductase Inhibition With Finasteride on Bone Mineral Density in Men: Results of a 4-Year Placebo Controlled Trial , 2002 .

[48]  R. Swerdloff,et al.  Should the nonaromatizable androgen dihydrotestosterone be considered as an alternative to testosterone in the treatment of the andropause? , 2002, The Journal of clinical endocrinology and metabolism.

[49]  O. Itkonen,et al.  The effects of transdermal dihydrotestosterone in the aging male: a prospective, randomized, double blind study. , 2002, The Journal of clinical endocrinology and metabolism.

[50]  David Handelsman,et al.  A randomised controlled clinical trial of antibiotic impregnation of testosterone pellet implants to reduce extrusion rate. , 2002, European journal of endocrinology.

[51]  R. Wolfe,et al.  Testosterone administration to older men improves muscle function: molecular and physiological mechanisms. , 2002, American journal of physiology. Endocrinology and metabolism.

[52]  A. Matsumoto Andropause: clinical implications of the decline in serum testosterone levels with aging in men. , 2002, The journals of gerontology. Series A, Biological sciences and medical sciences.

[53]  A. Matsumoto,et al.  Testosterone release from a subcutaneous, biodegradable microcapsule formulation (Viatrel) in hypogonadal men. , 2002, Journal of andrology.

[54]  A. Vermeulen,et al.  Diagnosis of hypogonadism in the aging male , 2002, The aging male : the official journal of the International Society for the Study of the Aging Male.

[55]  R. Casaburi,et al.  Testosterone dose-response relationships in healthy young men. , 2001, American journal of physiology. Endocrinology and metabolism.

[56]  David Handelsman,et al.  Influence of implantation site and track geometry on the extrusion rate and pharmacology of testosterone implants , 2001, Clinical endocrinology.

[57]  David Handelsman,et al.  A double-blind, placebo-controlled, randomized clinical trial of transdermal dihydrotestosterone gel on muscular strength, mobility, and quality of life in older men with partial androgen deficiency. , 2001, The Journal of clinical endocrinology and metabolism.

[58]  D. Siscovick,et al.  Intramuscular testosterone esters and plasma lipids in hypogonadal men: a meta-analysis. , 2001, The American journal of medicine.

[59]  A. Iranmanesh,et al.  Effects of transdermal testosterone gel on bone turnover markers and bone mineral density in hypogonadal men , 2001, Clinical endocrinology.

[60]  Keith C. Norris,et al.  Pharmacokinetics of a transdermal testosterone system in men with end stage renal disease receiving maintenance hemodialysis and healthy hypogonadal men. , 2001, The Journal of clinical endocrinology and metabolism.

[61]  A. Dobs,et al.  Hypogonadism and androgen replacement therapy in elderly men. , 2001, The American journal of medicine.

[62]  A. Kenny,et al.  Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels. , 2001, The journals of gerontology. Series A, Biological sciences and medical sciences.

[63]  E. Metter,et al.  Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. , 2001, The Journal of clinical endocrinology and metabolism.

[64]  A. Iranmanesh,et al.  Long-term pharmacokinetics of transdermal testosterone gel in hypogonadal men. , 2000, The Journal of clinical endocrinology and metabolism.

[65]  J. Mckinlay,et al.  Construction and field validation of a self‐administered screener for testosterone deficiency (hypogonadism) in ageing men , 2000, Clinical endocrinology.

[66]  R. Steeds,et al.  Chronic Stable Angina : A Randomized , Double-Blind , Placebo-Controlled Study Low-Dose Transdermal Testosterone Therapy Improves Angina Threshold in Men With , 2000 .

[67]  H. Perry,et al.  Validation of a screening questionnaire for androgen deficiency in aging males. , 2000, Metabolism: clinical and experimental.

[68]  A. Kenny,et al.  Determinants of bone density in healthy older men with low testosterone levels. , 2000, The journals of gerontology. Series A, Biological sciences and medical sciences.

[69]  J. Berlin,et al.  Effects of testosterone replacement in hypogonadal men. , 2000, The Journal of clinical endocrinology and metabolism.

[70]  A. Iranmanesh,et al.  Transdermal testosterone gel improves sexual function, mood, muscle strength, and body composition parameters in hypogonadal men. , 2000, The Journal of clinical endocrinology and metabolism.

[71]  E. Nieschlag,et al.  Hormone substitution in male hypogonadism , 2000, Molecular and Cellular Endocrinology.

[72]  R. Swerdloff,et al.  Pharmacokinetics of transdermal testosterone gel in hypogonadal men: application of gel at one site versus four sites: a General Clinical Research Center Study. , 2000, The Journal of clinical endocrinology and metabolism.

[73]  C. Mantzoros,et al.  Hormonal predictors of prostate cancer: a meta-analysis. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[74]  E. Nieschlag,et al.  Repeated intramuscular injections of testosterone undecanoate for substitution therapy in hypogonadal men , 1999, Clinical endocrinology.

[75]  J. Suvisaari,et al.  Pharmacokinetics of 7 alpha-methyl-19-nortestosterone (MENT) delivery using subdermal implants in healthy men. , 1999, Contraception.

[76]  D. Baird,et al.  7Alpha-methyl-19-nortestosterone maintains sexual behavior and mood in hypogonadal men. , 1999, The Journal of clinical endocrinology and metabolism.

[77]  S. Arver,et al.  Pharmacokinetics, efficacy, and safety of a permeation-enhanced testosterone transdermal system in comparison with bi-weekly injections of testosterone enanthate for the treatment of hypogonadal men. , 1999, The Journal of clinical endocrinology and metabolism.

[78]  David Handelsman,et al.  Extrusion of testosterone pellets: a randomized controlled clinical study , 1999, Clinical endocrinology.

[79]  A. Vermeulen,et al.  A critical evaluation of simple methods for the estimation of free testosterone in serum. , 1999, The Journal of clinical endocrinology and metabolism.

[80]  J. Suvisaari,et al.  Gonadotrophin and testosterone suppression by 7alpha-methyl-19-nortestosterone acetate administered by subdermal implant to healthy men. , 1999, Human reproduction.

[81]  J. Berlin,et al.  Effect of testosterone treatment on body composition and muscle strength in men over 65 years of age. , 1999, The Journal of clinical endocrinology and metabolism.

[82]  M. Horan,et al.  Difficulties in measuring the effect of testosterone replacement therapy on muscle function in older men. , 1999, International journal of andrology.

[83]  T. Key,et al.  Endogenous sex hormones and prostate cancer: a quantitative review of prospective studies , 1999, British Journal of Cancer.

[84]  J. Berlin,et al.  Effect of testosterone treatment on bone mineral density in men over 65 years of age. , 1999, The Journal of clinical endocrinology and metabolism.

[85]  E. Nieschlag,et al.  Intramuscular injection of testosterone undecanoate for the treatment of male hypogonadism: phase I studies. , 1999, European journal of endocrinology.

[86]  M. Schubert,et al.  Influence of various modes of androgen substitution on serum lipids and lipoproteins in hypogonadal men. , 1999, Metabolism: clinical and experimental.

[87]  E. Nieschlag,et al.  Long‐term substitution therapy of hypogonadal men with transscrotal testosterone over 7–10 years , 1999, Clinical endocrinology.

[88]  M. Armitage,et al.  Experience with transdermal testosterone replacement therapy for hypogonadal men , 1999, Clinical endocrinology.

[89]  D. Cummings,et al.  Prostate-sparing effects in primates of the potent androgen 7alpha-methyl-19-nortestosterone: a potential alternative to testosterone for androgen replacement and male contraception. , 1998, The Journal of clinical endocrinology and metabolism.

[90]  W. Bremner,et al.  A pharmacokinetic study of injectable testosterone undecanoate in hypogonadal men. , 1998, Journal of andrology.

[91]  B. Goodpaster,et al.  The analog free testosterone assay: are the results in men clinically useful? , 1998, Clinical chemistry.

[92]  J. Bilezikian,et al.  Increased bone mass as a result of estrogen therapy in a man with aromatase deficiency. , 1998, The New England journal of medicine.

[93]  A. Iranmanesh,et al.  Comparative pharmacokinetics of three doses of percutaneous dihydrotestosterone gel in healthy elderly men--a clinical research center study. , 1998, The Journal of clinical endocrinology and metabolism.

[94]  D. Jorkasky,et al.  Use of topical corticosteroid pretreatment to reduce the incidence and severity of skin reactions associated with testosterone transdermal therapy. , 1998, Clinical therapeutics.

[95]  S. Arver,et al.  Long‐term efficacy and safety of a permeation‐enhanced testosterone transdermal system in hypogonadal men , 1997, Clinical endocrinology.

[96]  Zhiling Yu,et al.  Transdermal Testosterone Administration in Hypogonadal Men: Comparison of Pharmacokinetics at Different Sites of Application and at the First and Fifth Days of Application , 1997, Journal of clinical pharmacology.

[97]  Zhiling Yu,et al.  Testosterone Pharmacokinetics after Application of an Investigational Transdermal System in Hypogonadal Men , 1997, Journal of clinical pharmacology.

[98]  J. Morley,et al.  Outcomes of long-term testosterone replacement in older hypogonadal males: a retrospective analysis. , 1997, The Journal of clinical endocrinology and metabolism.

[99]  I. Thompson,et al.  The effect of parenteral testosterone replacement on prostate specific antigen in hypogonadal men with erectile dysfunction. , 1997, The Journal of urology.

[100]  David Handelsman,et al.  An analysis of testosterone implants for androgen replacement therapy , 1997, Clinical endocrinology.

[101]  T. Link,et al.  Long-term effect of testosterone therapy on bone mineral density in hypogonadal men. , 1997, The Journal of clinical endocrinology and metabolism.

[102]  M. Zacharin,et al.  Treatment of hypogonadal adolescent boys with long acting subcutaneous testosterone pellets , 1997, Archives of disease in childhood.

[103]  H. Perry,et al.  Testosterone replacement in older hypogonadal men: a 12-month randomized controlled trial. , 1997, The Journal of clinical endocrinology and metabolism.

[104]  M. Lundie,et al.  Testosterone supplementation for hypogonadal impotence: assessment of biochemical measures and therapeutic outcomes. , 1997, The Journal of urology.

[105]  R. Casaburi,et al.  Testosterone replacement increases fat-free mass and muscle size in hypogonadal men. , 1997, The Journal of clinical endocrinology and metabolism.

[106]  W. DeWolf,et al.  Occult prostate cancer in men with low serum testosterone levels. , 1996, JAMA.

[107]  D. Schoenfeld,et al.  Increase in bone density and lean body mass during testosterone administration in men with acquired hypogonadism. , 1996, The Journal of clinical endocrinology and metabolism.

[108]  R. Swerdloff,et al.  Testosterone replacement therapy improves mood in hypogonadal men--a clinical research center study. , 1996, The Journal of clinical endocrinology and metabolism.

[109]  K. Nair,et al.  Effects of testosterone replacement on muscle mass and muscle protein synthesis in hypogonadal men--a clinical research center study. , 1996, The Journal of clinical endocrinology and metabolism.

[110]  A. Iranmanesh,et al.  Sublingual testosterone replacement improves muscle mass and strength, decreases bone resorption, and increases bone formation markers in hypogonadal men--a clinical research center study. , 1996, The Journal of clinical endocrinology and metabolism.

[111]  F. Jockenhövel,et al.  Pharmacokinetics and pharmacodynamics of subcutaneous testosterone implants in hypogonadal men , 1996, Clinical endocrinology.

[112]  M. Vallotton Primary aldosteronism. Part II Differential diagnosis of primary hyperaldosteronism and pseudoaldosteronism , 1996, Clinical endocrinology.

[113]  S. Arver,et al.  Pharmacokinetics and metabolism of a permeation-enhanced testosterone transdermal system in hypogonadal men: influence of application site- -a clinical research center study. , 1996, The Journal of clinical endocrinology and metabolism.

[114]  S. Arver,et al.  Improvement of sexual function in testosterone deficient men treated for 1 year with a permeation enhanced testosterone transdermal system. , 1996, The Journal of urology.

[115]  W. Bremner,et al.  Androgens in men--uses and abuses. , 1996, The New England journal of medicine.

[116]  S. Lim,et al.  Site-specific effect of testosterone on bone mineral density in male hypogonadism. , 1995, Journal of Korean medical science.

[117]  E. Simpson,et al.  Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of estrogens. , 1995, The Journal of clinical endocrinology and metabolism.

[118]  G. Alexander,et al.  Pharmacokinetics, bioefficacy, and safety of sublingual testosterone cyclodextrin in hypogonadal men: comparison to testosterone enanthate--a clinical research center study. , 1995, The Journal of clinical endocrinology and metabolism.

[119]  David Handelsman,et al.  Andrology: Tolerability of intramuscular injections of testosterone ester in oil vehicle , 1995 .

[120]  O. Arisaka,et al.  Effect of testosterone on bone density and bone metabolism in adolescent male hypogonadism. , 1995, Metabolism: clinical and experimental.

[121]  K. Korach,et al.  Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. , 1994, The New England journal of medicine.

[122]  B. de Lignières,et al.  Transdermal dihydrotestosterone treatment of 'andropause'. , 1993 .

[123]  H. Perry,et al.  Effects of Testosterone Replacement Therapy in Old Hypogonadal Males: A Preliminary Study , 1993, Journal of the American Geriatrics Society.

[124]  E. Nieschlag,et al.  Testosterone buciclate (20 Aet-1) in hypogonadal men: pharmacokinetics and pharmacodynamics of the new long-acting androgen ester. , 1992, The Journal of clinical endocrinology and metabolism.

[125]  J. S. Tenover,et al.  Effects of testosterone supplementation in the aging male. , 1992, The Journal of clinical endocrinology and metabolism.

[126]  J. Devogelaer,et al.  Low bone mass in hypogonadal males. Effect of testosterone substitution therapy, a densitometric study. , 1992, Maturitas.

[127]  M. Riggs,et al.  Testosterone Deficiency As a Risk Factor for Hip Fractures in Men: A Case‐Control Study , 1992, The American journal of the medical sciences.

[128]  C. Bardin,et al.  The biological activity of 7 alpha-methyl-19-nortestosterone is not amplified in male reproductive tract as is that of testosterone. , 1992, Endocrinology.

[129]  K. Tolman,et al.  Enhanced transdermal delivery of testosterone across nonscrotal skin produces physiological concentrations of testosterone and its metabolites in hypogonadal men. , 1992, The Journal of clinical endocrinology and metabolism.

[130]  S. Yen,et al.  Sublingual administration of testosterone-hydroxypropyl-beta-cyclodextrin inclusion complex simulates episodic androgen release in hypogonadal men. , 1991, The Journal of clinical endocrinology and metabolism.

[131]  S. Posen,et al.  Effects of testosterone and venesection on spinal and peripheral bone mineral in six hypogonadal men with hemochromatosis , 1991, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[132]  M. Rajalakshmi,et al.  Pharmacokinetics and pharmacodynamics of a new long-acting androgen ester: maintenance of physiological androgen levels for 4 months after a single injection. , 1989, Contraception.

[133]  W. Bremner,et al.  Circadian variation in testosterone, sex hormone-binding globulin, and calculated non-sex hormone-binding globulin bound testosterone in healthy young and elderly men. , 1989, Journal of andrology.

[134]  J. Findlay,et al.  Treatment of primary hypogonadism in men by the transdermal administration of testosterone. , 1989, The Journal of clinical endocrinology and metabolism.

[135]  W. Crowley,et al.  Increases in bone density during treatment of men with idiopathic hypogonadotropic hypogonadism. , 1988, The Journal of clinical endocrinology and metabolism.

[136]  L. Ewing,et al.  Initial trial of slow-release testosterone microspheres in hypogonadal men. , 1988, Fertility and sterility.

[137]  David Handelsman,et al.  Randomized clinical trial of testosterone replacement therapy in hypogonadal men. , 1988, International journal of andrology.

[138]  M. Vance,et al.  Transdermal testosterone treatment of hypogonadal men. , 1988, The Journal of urology.

[139]  K. Langer,et al.  Substitution therapy of hypogonadal men with transdermal testosterone over one year. , 1988, Acta endocrinologica.

[140]  R. Santen,et al.  Transdermal testosterone therapy in the treatment of male hypogonadism. , 1988, The Journal of clinical endocrinology and metabolism.

[141]  H. Nankin Hormone kinetics after intramuscular testosterone cypionate. , 1987, Fertility and sterility.

[142]  W. Crowley,et al.  Osteoporosis in Men with Idiopathic Hypogonadotropic Hypogonadism , 1987 .

[143]  A. Klibanski,et al.  Osteoporosis in men with hyperprolactinemic hypogonadism. , 1986, Annals of internal medicine.

[144]  M. Vitiello,et al.  Loss of circadian rhythmicity in blood testosterone levels with aging in normal men. , 1983, The Journal of clinical endocrinology and metabolism.

[145]  J. Fiet,et al.  Percutaneous absorption of 5 alpha-dihydrotestosterone in man. II. Percutaneous administration of 5 alpha-dihydrotestosterone in hypogonadal men with idiopathic haemochromatosis; clinical, metabolic and hormonal effectiveness. , 1982, International journal of andrology.

[146]  J. Fiet,et al.  Percutaneous absorption of 5α-dihydrotestosterone in man.: I. Plasma androgen and gonadotrophin levels in normal adult men after percutaneous administration of 5α-dihydrotestosterone , 1982 .

[147]  P. Snyder,et al.  Treatment of male hypogonadism with testosterone enanthate. , 1980, The Journal of clinical endocrinology and metabolism.

[148]  E. Nieschlag,et al.  Comparison of testosterone, dihydrotestosterone, luteinizing hormone, and follicle-stimulating hormone in serum after injection of testosterone enanthate of testosterone cypionate. , 1980, Fertility and sterility.

[149]  A. Kenny,et al.  Effects of testosterone on behavior, depression, and cognitive function in older men with mild cognitive loss. , 2004, The journals of gerontology. Series A, Biological sciences and medical sciences.

[150]  A. Morales,et al.  Androgen deficiency in the aging male. , 2003, International journal of impotence research.

[151]  A. Siegel,et al.  Testosterone gel supplementation for men with refractory depression: a randomized, placebo-controlled trial. , 2003, The American journal of psychiatry.

[152]  T. Link,et al.  Effects of testosterone replacement therapy on cortical and trabecular bone mineral density, vertebral body area and paraspinal muscle area in hypogonadal men. , 1998, European journal of endocrinology.

[153]  M. Tschöp,et al.  A Time-Resolved Fluorescence Immunoassay for the Measurement of Testosterone in Saliva: Monitoring of Testosterone Replacement Therapy with Testosterone Buciclate , 1998, Clinical chemistry and laboratory medicine.

[154]  W. Jordan,et al.  Comparison of the skin irritation potential of two testosterone transdermal systems: an investigational system and a marketed product. , 1998, Clinical therapeutics.

[155]  A. Dobs,et al.  Pharmacokinetic characteristics, efficacy, and safety of buccal testosterone in hypogonadal males: a pilot study. , 1998, The Journal of clinical endocrinology and metabolism.

[156]  M. Pandian,et al.  A biodegradable testosterone microcapsule formulation provides uniform eugonadal levels of testosterone for 10-11 weeks in hypogonadal men. , 1992, The Journal of clinical endocrinology and metabolism.

[157]  H. Croxatto,et al.  Pharmacokinetics and metabolism of RU 486. , 1987, Journal of steroid biochemistry.