The relationship between testosterone levels, the metabolic syndrome (by two criteria), and insulin resistance in a population of men with organic erectile dysfunction.
J Sex Med. 2007 Jul;4(4 Pt 1):1046-55.
Guay A, Jacobson J.
Department of Endocrinology/Center for Sexual Function, Lahey Clinic Northshore, One Essex Center Drive, Peabody, MA 01960, USA. email@example.com
INTRODUCTION: Erectile dysfunction (ED) in men increases with age, as does cardiovascular disease (CVD). Major risk factors of CVD are similar to ED, including insulin resistance (IR) and metabolic syndrome (MS). Hypogonadism has been associated with MS and IR in general populations. AIM: To determine the association between hypogonadism and MS and/or IR in men with ED, and to determine if hypogonadism is related to these cardiovascular (CV) risks. MAIN OUTCOME MEASURES: To compare the mean testosterone levels in men with and without IR and MS, and to show the difference in hypogonadism prevalence in mutually exclusive definitions of MS. METHODS: Mean testosterone for the National Cholesterol Education Program (NCEP) and the World Health Organization (WHO) criteria of MS were calculated using independent t-tests. Multiple range t-tests were used to compare and contrast four groups: (i) only NCEP-Third Adult Treatment Panel criteria; (ii) only the WHO criteria; (iii) men with no MS; and (iv) men fulfilling both MS definitions. Chi-squared analysis was employed to determine the association of hypogonadism with IR. RESULTS: The prevalence of IR was 79% and of MS was 35 % by the WHO but 43% by the NCEP. Differences in point prevalences were negligible when mutually exclusive groups of MS were compared. Mean free testosterone was lower for the WHO MS or the WHO and NCEP MS (P = 0.04) but not for only the NCEP MS criteria. IR was significantly associated with low free testosterone and hypogonadism (P = 0.02 for each). If more than one criteria were present for either the WHO or NCEP MS, free testosterone was lower (P = 0.02). CONCLUSION: MS and IR are strongly associated with lower testosterone and hypogonadism. The WHO criteria are a more sensitive indicator of MS and may predict ED better. Men with ED should not only have CV risks evaluated, but should also have testosterone levels drawn.
NCEP-ATPIII-defined metabolic syndrome, type 2 diabetes mellitus, and prevalence of hypogonadism in male patients with sexual dysfunction.
Corona G, Mannucci E, Petrone L, Balercia G, Paggi F, Fisher AD, Lotti F, Chiarini V, Fedele D, Forti G, Maggi M.
Andrology Unit, Department of Clinical Physiopathology, University of Florence, Fiale Pieraccini 6, 50139 Florence, Italy.
INTRODUCTION: Type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) are characterized by insulin resistance and often associated with male hypogonadism. AIM: To discriminate the specific contribution of T2DM and MetS to male hypogonadism. METHODS: A consecutive series of 1,134 (mean age 52.1 +/- 13 years) male patients with sexual dysfunction was studied. MAIN OUTCOME MEASURES: Several hormonal and biochemical parameters were studied along with ANDROTEST, a 12-item validated structured interview, specifically designed for the screening of hypogonadism (total testosterone [TT] <10.4 nmol/L or free testosterone [FT] <37 pmol/L) in a male population with sexual dysfunction. RESULTS: Irrespective of the criteria used to define hypogonadism, MetS was associated with a significantly higher prevalence of the condition, both in subjects with and without T2DM (41% and 29% vs. 13.2% and 77.1% and 58% vs. 40.6%, respectively, for TT and FT in patients with MetS and with or without T2DM, when compared with subjects without MetS and T2DM; both P < 0.0001). Conversely, T2DM was associated with a higher prevalence of hypogonadism in subjects with MetS but not in those without MetS. Patients with MetS, with or without T2DM, also showed a higher ANDROTEST score when compared with patients without MetS. Logistic multivariate regression analysis, incorporating the five components of MetS, identified a significant association of elevated waist circumference and hypertriglyceridemia with hypogonadism both in patients, with or without T2DM. CONCLUSIONS: Our study demonstrated that MetS, and in particular visceral adiposity (as assessed by increased waistline and hypertriglyceridemia), is specifically associated with hypogonadism in subjects consulting for sexual dysfunction.
A comparison of NCEP-ATPIII and IDF metabolic syndrome definitions with relation to metabolic syndrome-associated sexual dysfunction.
J Sex Med. 2007 May;4(3):789-96.
Corona G, Mannucci E, Petrone L, Schulman C, Balercia G, Fisher AD, Chiarini V, Forti G, Maggi M.
Andrology Unit, Department of Clinical Physiopathology, University of Florence, Florence, Italy.
INTRODUCTION: Metabolic syndrome (MetS) is a clustering of cardiovascular and metabolic risk factors, often associated with erectile dysfunction (ED) and hypogonadism. Recently, the International Diabetes Federation (IDF) proposed a substantial revision of the National Cholesterol Education Program-Third Adult Treatment Panel (NCEP-ATPIII) MetS criteria, essentially lowering the diagnostic cutoff values. Aim. To investigate the associations between these two recently proposed definitions of MetS with the relative risk of arteriogenic ED and hypogonadism in a large cohort of patients with male sexual dysfunction. METHODS: A consecutive series of 1086 patients with sexual dysfunction (mean age 51.9 +/- 12.8 years) was studied. MAIN OUTCOME MEASURES: Several hormonal, biochemical, and instrumental (penile Doppler ultrasound) parameters were studied, along with ANDROTEST, a 12-item validated structured interview, specifically designed for the screening hypogonadism in a sexual dysfunction population. In particular, a score >8 is predictive of low testosterone (<10.4 nmol/L) with a sensitivity and specificity of about 70%. RESULTS: The prevalence of MetS was 32.0% and 44.7% according to NCEP-ATPIII and IDF criteria, respectively. After adjustment for confounding factors, only NCEP-ATPIII was significantly associated with dynamic prostaglandin E(1)-stimulated penile flow (Vpmax, B = -7.7 +/- 3.8; P < 0.05). Patients with MetS defined according to both criteria reported lower total and free testosterone levels, higher prevalence of hypogonadism, and higher ANDROTEST score. However, when IDF, but not NCEP-ATPIII, criteria were fulfilled, the prevalence of hypogonadism was significantly lower than that observed in patients fulfilling both criteria (15.6% vs. 34.8%, respectively; P < 0.00001). Conversely, patients fulfilling NCEP-ATPIII, but not IDF, criteria did not show a significant different prevalence of hypogonadism than those positive for both sets of criteria (30.8% vs. 34.8%; P = NS). CONCLUSIONS: In patients with ED, NCEP-ATPIII criteria seem to be a better predictor of hypogonadism and impaired penile blood flow than IDF ones.
Urology. 2008 Feb 28
Kohler TS, Kim J, Feia K, Bodie J, Johnson N, Makhlouf A, Monga M.
Department of Urologic Surgery, University of Minnesota School of Medicine, Minneapolis, Minnesota.
OBJECTIVES: Erectile dysfunction (ED) and androgen deficiency in aging men are two separate clinical entities that often overlap. Controversy exists regarding the most appropriate total testosterone level that defines androgen deficiency in aging men, and its prevalence in men with ED is still uncertain. We evaluated the prevalence and risk factors of low and low-normal testosterone levels in men presenting for an initial ED evaluation. METHODS: The computerized charts from 1987 to 2002 of 2794 men aged 25 to 80 years and presenting with a primary complaint of ED who also had serum total testosterone levels measured were retrospectively reviewed. Multiple testosterone level cutpoints and a linear regression model (including age, diabetes, cholesterol, anemia, creatinine, and prostate-specific antigen) were used to analyze the factors that correlated with hypogonadism. RESULTS: The prevalence of androgen deficiency was 7%, 23%, 33%, and 47% for testosterone levels of less than 200, less than 300, less than 346, and less than 400 ng/dL, respectively. An abrupt increase in hypogonadism prevalence occurred in men aged 45 to 50, beyond which a plateau of prevalence was maintained until older than 80 years of age. Age, the presence of uncontrolled diabetes, high total cholesterol, and anemia all correlated with significantly decreased testosterone levels in men with ED. The prostate-specific antigen level and creatinine did not affect the testosterone levels. CONCLUSIONS: Androgen deficiency was quite common in men presenting with ED and correlated significantly with age, uncontrolled diabetes, hypercholesteremia, and anemia. Although additional prospective studies evaluating the effect of testosterone supplementation in this population are needed, clinicians, including urologists, should be keenly aware of the large overlap of patients with ED who might also have the entity, androgen deficiency in the aging male.
Role of endogenous androgen against insulin resistance and athero- sclerosis in men with type 2 diabetes.
Curr Diabetes Rev. 2007 Feb;3(1):25-31.
Fukui M, Kitagawa Y, Ose H, Hasegawa G, Yoshikawa T, Nakamura N.
Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. firstname.lastname@example.org
Age-related decline in serum testosterone and dehydroepiandrosterone sulfate concentrations occur in men. Low concentrations of these endogenous androgens have been linked with insulin resistance, which is an important upstream driver for metabolic abnormalities such as hyperglycemia, hypertension, or hyperlipidemia, and increased cardiovascular risk. Moreover, men with diabetes have significantly less circulating androgen than nondiabetic men. Here, we summarize how androgen affects insulin resistance and atherosclerosis in men with type 2 diabetes. Low serum concentrations of endogenous androgens are associated with visceral fat accumulation. Androgen deprivation by castration to treat prostate cancer increases insulin resistance, while testosterone administration in type 2 diabetic men with androgen deficiency improves glucose homeostasis and decreases visceral fat, in addition to alleviating symptoms of androgen deficiency including erectile dysfunction. Androgen correlates inversely with severity of atherosclerosis and has beneficial effects upon vascular reactivity, inflammatory cytokine, adhesion molecules, insulin resistance, serum lipids, and hemostatic factors. Because men with type 2 diabetes have relative hypogonadism, testosterone supplementation could decrease both insulin resistance and atherosclerosis.
Curr Opin Endocrinol Diabetes Obes. 2007 Jun;14(3):226-34.
Kalyani RR, Dobs AS.
Division of Endocrinology and Metabolism, Johns Hopkins School of Medicine, Baltimore, Maryland 21287, USA.
PURPOSE OF REVIEW: The burden of androgen deficiency in men with diabetes and the metabolic syndrome has become increasingly apparent in population-based studies. This article focuses on the mechanisms underlying the interdependent relationship between these conditions. RECENT FINDINGS: Various definitions of hypogonadism, the metabolic syndrome and diabetes have been proposed and are used in the literature. Cross-sectional studies have found that between 20 and 64% of men with diabetes have hypogonadism, with higher prevalence rates found in the elderly. Hypogonadism can be a risk factor for the development of diabetes and the metabolic syndrome through various mechanisms including changes in body composition; androgen receptor polymorphisms; glucose transport; and reduced antioxidant effect. Conversely, diabetes and the metabolic syndrome can be risk factors for hypogonadism through some similar but mostly distinct mechanisms, such as increased body weight; decreased sex hormone binding globulin levels; suppression of gonadotrophin release or Leydig cell testosterone production; cytokine-mediated inhibition of testicular steroid production; and increased aromatase activity contributing to relative estrogen excess. SUMMARY: The relationship between diabetes, the metabolic syndrome and androgen deficiency is complex. Testosterone supplementation, by either oral or intramuscular routes and through exogenous or endogenous delivery, has a promising role in this population although further clinical trials are needed.
Aging Male. 2007 Jun;10(2):53-6.
Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.
Evidence is presented to link components of the metabolic syndrome to testosterone deficiency and obesity. Testosterone deficiency in hypogonadism or testosterone deprivation in normo-gonadotropic men increases fat mass as well as fasting insulin levels. Testosterone supplementation (TS) in a dose dependent manner, increase lean body mass (LBM), reduces fat mass, body mass index (BMI) and waist hip ratio in both young and elderly hypogonadal men. A negative association between T and insulin resistance as well as impaired glucose intolerance has been demonstrated and in type 2 diabetic men TS improves metabolic parameters. TS improves most components of the metabolic syndrome and also reduces inflammatory cytokines.
Increasing insulin resistance is associated with a decrease in Leydig cell testosterone secretion in men.
J Clin Endocrinol Metab. 2005 May;90(5):2636-41. Epub 2005 Feb 15.
Pitteloud N, Hardin M, Dwyer AA, Valassi E, Yialamas M, Elahi D, Hayes FJ.
Reproductive Endocrine Unit, BHX 511, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts 02114, USA.
Insulin resistance is associated with low testosterone (T) levels in men, the mechanism of which is unclear. Thus, the aim of this study was to evaluate the hypothalamic-pituitary-gonadal axis in men with a spectrum of insulin sensitivity. Twenty-one men (aged 25-65 yr) had a glucose tolerance test and assessment of insulin sensitivity using a hyperinsulinemic-euglycemic clamp. Insulin sensitivity, expressed as the M value (milligrams per kilograms(-1) per minute(-1)), was calculated from the glucose disposal rate during the final 30 min of the clamp. Eighteen subjects had blood sampling every 10 min for 12 h to assess LH pulsatility. Hypogonadism was then induced with a GnRH antagonist, followed by sequential stimulation testing with GnRH (750 ng/kg, iv) and human chorionic gonadotropin (hCG; 1000 IU, im) to assess pituitary and testicular responsiveness, respectively. Nine subjects had normal glucose tolerance, nine had impaired glucose tolerance, and three had diabetes mellitus. There was a positive relationship between M and T levels (r = 0.46; P < 0.05). No relationship was seen between M and parameters of LH secretion, including mean LH levels, LH pulse amplitude, LH pulse frequency, and LH response to exogenous GnRH administration. In contrast, a strong correlation was observed between M and the T response to hCG (r = 0.73; P < 0.005). Baseline T levels correlated with the increase in T after hCG administration (r = 0.47; P < 0.05). During the clamp, T levels increased from a baseline level of 367 +/- 30 to 419 +/- 38 ng/dl during the last 30 min (P < 0.05). From these data we conclude that insulin resistance is associated with a decrease in Leydig cell T secretion in men. Additional studies are required to determine the mechanism of this effect.
Acute sex steroid withdrawal reduces insulin sensitivity in healthy men with idiopathic hypogonadotropic hypogonadism.
J Clin Endocrinol Metab. 2007 Nov;92(11):4254-9. Epub 2007 Aug 28.
Yialamas MA, Dwyer AA, Hanley E, Lee H, Pitteloud N, Hayes FJ.
Reproductive Endocrine Unit of the Department of Medicine , Massachusetts General Hospital, Bartlett Hall Extension 511, Boston, Massachusetts 02114, USA.CONTEXT: Evidence suggests that testosterone (T) influences insulin sensitivity in men. The mechanism of this effect is unclear but is thought to involve changes in body composition. OBJECTIVE: The aim of this study was to determine whether acute sex steroid withdrawal decreases insulin sensitivity in young, healthy men with idiopathic hypogonadotropic hypogonadism (IHH). DESIGN: This was a 2-wk prospective study. SETTING: The study was conducted at a General Clinical Research Center. PATIENTS: Twelve men with IHH (age 40.8 +/- 2.8 yr) were studied: 1) on hormone replacement with normal T levels and 2) 2 wk after discontinuing therapy. MAIN OUTCOME MEASURES: Each evaluation comprised a 75-g oral glucose tolerance test with assessment of insulin sensitivity (fasting insulin levels, homeostatic model assessment for insulin resistance, and Matsuda insulin sensitivity index) and insulin secretion (corrected insulin response). Serum cortisol, leptin, adiponectin, free fatty acids, IL-6, C-reactive protein, and TNF-alpha levels were also measured. RESULTS: Body mass index was unchanged (27.1 +/- 1.1 to 27.2 +/- 1.1 kg/m(2)). Serum T levels decreased from 529 +/- 65 to 28 +/- 8 ng/dl (P < 0.00005). Fasting insulin levels increased from 4.9 +/- 0.7 to 6.2 +/- 0.6 microU/ml (P = 0.005), homeostatic model assessment of insulin resistance increased from 1.07 +/- 0.2 to 1.4 +/- 1.01 (P < 0.005), and insulin sensitivity index decreased from 11.0 +/- 2.3 to 7.5 +/- 0.7 (P < 0.05). There was a trend for fasting glucose levels to increase, 86.7 +/- 1.3 to 90.8 +/- 1.7 mg/dl (P = 0.09). IL-6 levels increased from 1.2 +/- 0.2 to 2.4 +/- 0.5 pg/ml (P < 0.01), whereas TNF-alpha levels decreased from 1.0 +/- 0.1 to 0.6 +/- 0.1 pg/ml (P < 0.05). No other significant changes were observed. CONCLUSIONS: 1) Acute sex steroid withdrawal reduces insulin sensitivity in young healthy IHH men. 2) The acuity of the hypogonadism and absence of changes in body mass index or leptin levels suggest that sex steroids modulate insulin sensitivity in the absence of apparent or detectable changes in body composition.
N Engl J Med. 2007 Aug 30;357(9):863-73.
N Engl J Med. 2007 Aug 30;357(9):929-32.
Raivio T, Falardeau J, Dwyer A, Quinton R, Hayes FJ, Hughes VA, Cole LW, Pearce SH, Lee H, Boepple P, Crowley WF Jr, Pitteloud N.
Harvard Center for Reproductive Endocrine Sciences and the Reproductive Endocrine Unit of the Department of Medicine, Massachusetts General Hospital, Boston 02114, USA.
BACKGROUND: Idiopathic hypogonadotropic hypogonadism, which may be associated with anosmia (the Kallmann syndrome) or with a normal sense of smell, is a treatable form of male infertility caused by a congenital defect in the secretion or action of gonadotropin-releasing hormone (GnRH). Patients have absent or incomplete sexual maturation by the age of 18. Idiopathic hypogonadotropic hypogonadism was previously thought to require lifelong therapy. We describe 15 men in whom reversal of idiopathic hypogonadotropic hypogonadism was sustained after discontinuation of hormonal therapy. METHODS: We defined the sustained reversal of idiopathic hypogonadotropic hypogonadism as the presence of normal adult testosterone levels after hormonal therapy was discontinued. RESULTS: Ten sustained reversals were identified retrospectively. Five sustained reversals were identified prospectively among 50 men with idiopathic hypogonadotropic hypogonadism after a mean (+/-SD) duration of treatment interruption of 6+/-3 weeks. Of the 15 men who had a sustained reversal, 4 had anosmia. At initial evaluation, 6 men had absent puberty, 9 had partial puberty, and all had abnormal secretion of GnRH-induced luteinizing hormone. All 15 men had received previous hormonal therapy to induce virilization, fertility, or both. Among those whose hypogonadism was reversed, the mean serum level of endogenous testosterone increased from 55+/-29 ng per deciliter (1.9+/-1.0 nmol per liter) to 386+/-91 ng per deciliter (13.4+/-3.2 nmol per liter, P<0.001), the luteinizing hormone level increased from 2.7+/-2.0 to 8.5+/-4.6 IU per liter (P<0.001), the level of follicle-stimulating hormone increased from 2.5+/-1.7 to 9.5+/-12.2 IU per liter (P<0.01), and testicular volume increased from 8+/-5 to 16+/-7 ml (P<0.001). Pulsatile luteinizing hormone secretion and spermatogenesis were documented. CONCLUSIONS: Sustained reversal of normosmic idiopathic hypogonadotropic hypogonadism and the Kallmann syndrome was noted after discontinuation of treatment in about 10% of patients with either absent or partial puberty. Therefore, brief discontinuation of hormonal therapy to assess reversibility of hypogonadotropic hypogonadism is reasonable.
J Clin Endocrinol Metab. 2008 Jan;93(1):68-75. Epub 2007 Oct 2.
J Clin Endocrinol Metab. 2008 Jan;93(1):32-3.
Laughlin GA, Barrett-Connor E, Bergstrom J.
Department of Family and Preventive Medicine, School of Medicine, University of California, San Diego, 9500 Gilman Drive, MC 0631C, La Jolla, California 92093, USA. email@example.comCONTEXT: Declining testosterone levels in elderly men are thought to underlie many of the symptoms and diseases of aging; however, studies demonstrating associations of low testosterone with clinical outcomes are few. OBJECTIVE: The objective of the study was to examine the association of endogenous testosterone levels with mortality in older community-dwelling men. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective, population-based study of 794 men, aged 50-91 (median 73.6) yr who had serum testosterone measurements at baseline (1984-1987) and were followed for mortality through July 2004. MAIN OUTCOME MEASURE: All-cause mortality by serum testosterone level was measured. RESULTS: During an average 11.8-yr follow-up, 538 deaths occurred. Men whose total testosterone levels were in the lowest quartile (<241 ng/dl) were 40% [hazards ratio (HR) 1.40; 95% confidence interval (CI) 1.14-1.71] more likely to die than those with higher levels, independent of age, adiposity, and lifestyle. Additional adjustment for health status markers, lipids, lipoproteins, blood pressure, glycemia, adipocytokines, and estradiol levels had minimal effect on results. The low testosterone-mortality association was also independent of the metabolic syndrome, diabetes, and prevalent cardiovascular disease but was attenuated by adjustment for IL-6 and C-reactive protein. In cause-specific analyses, low testosterone predicted increased risk of cardiovascular (HR 1.38; 95% CI 1.02-1.85) and respiratory disease (HR 2.29; 95% CI 1.25-4.20) mortality but was not significantly related to cancer death (HR 1.34; 95% CI 0.89-2.00). Results were similar for bioavailable testosterone. CONCLUSIONS: Testosterone insufficiency in older men is associated with increased risk of death over the following 20 yr, independent of multiple risk factors and several preexisting health conditions.
Testosterone therapy in adult men with androgen deficiency syndromes: an endocrine society clinical practice guideline.
J Clin Endocrinol Metab. 2006 Jun;91(6):1995-2010. Epub 2006 May 23.
Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, Montori VM.
Boston University School of Medicine (S.B.), Boston, Massachusetts 02118, USA.
OBJECTIVE: The objective was to provide guidelines for the evaluation and treatment of androgen deficiency syndromes in adult men. PARTICIPANTS: The Task Force was composed of a chair, selected by the Clinical Guidelines Subcommittee of The Endocrine Society, five additional experts, a methodologist, and a professional writer. The Task Force received no corporate funding or remuneration. EVIDENCE: The Task Force used systematic reviews of available evidence to inform its key recommendations. The Task Force used consistent language and graphical descriptions of both the strength of recommendation and the quality of evidence, using the recommendations of the Grading of Recommendations, Assessment, Development, and Evaluation group. CONSENSUS PROCESS: Consensus was guided by systematic reviews of evidence and discussions during three group meetings, several conference calls, and e-mail communications. The drafts prepared by the panelists with the help of a professional writer were reviewed successively by The Endocrine Society's Clinical Guidelines Subcommittee, Clinical Affairs Committee, and Council. The version approved by the Council was placed on The Endocrine Society's web site for comments by members. At each stage of review, the Task Force received written comments and incorporated needed changes. CONCLUSIONS: We recommend making a diagnosis of androgen deficiency only in men with consistent symptoms and signs and unequivocally low serum testosterone levels. We suggest the measurement of morning total testosterone level by a reliable assay as the initial diagnostic test. We recommend confirmation of the diagnosis by repeating the measurement of morning total testosterone and in some patients by measurement of free or bioavailable testosterone level, using accurate assays. We recommend testosterone therapy for symptomatic men with androgen deficiency, who have low testosterone levels, to induce and maintain secondary sex characteristics and to improve their sexual function, sense of well-being, muscle mass and strength, and bone mineral density. We recommend against starting testosterone therapy in patients with breast or prostate cancer, a palpable prostate nodule or induration or prostate-specific antigen greater than 3 ng/ml without further urological evaluation, erythrocytosis (hematocrit > 50%), hyperviscosity, untreated obstructive sleep apnea, severe lower urinary tract symptoms with International Prostate Symptom Score (IPSS) greater than 19, or class III or IV heart failure. When testosterone therapy is instituted, we suggest aiming at achieving testosterone levels during treatment in the mid-normal range with any of the approved formulations, chosen on the basis of the patient's preference, consideration of pharmacokinetics, treatment burden, and cost. Men receiving testosterone therapy should be monitored using a standardized plan.
A clinical trial of injectable testosterone undecanoate as a potential male contraceptive in normal Chinese men.
J Clin Endocrinol Metab. 1999 Oct;84(10):3642-7.
Zhang GY, Gu YQ, Wang XH, Cui YG, Bremner WJ.
Department of Endocrinology, National Research Institute for Family Planning, Beijing, China.
This is a pilot dose-finding study of spermatogenic suppression using testosterone undecanoate (TU) injections alone in normal Chinese men. Thirty-two healthy men were recruited. Volunteers underwent pretreatment evaluation, then a treatment period in which group I (n = 13) received 500 mg TU, group II (n = 12) received 1000 mg TU, and group III (n = 7) received placebo, respectively, at monthly intervals during the treatment period (or until azoospermia was achieved). Thereafter, they underwent a recovery period until all parameters returned to pretreatment levels. Eleven of 12 volunteers in the 500-mg TU group, and all volunteers in the 1000-mg TU group became azoospermic. Faster suppression of spermatogenesis was achieved in the 1000-mg TU group. Serum testosterone increased significantly in the higher dose group at weeks 8 and 12, but remained within the normal range. Mean serum LH and FSH were profoundly suppressed by both doses to undetectable levels at week 16. TU injections did not cause a significant change in high density lipoprotein cholesterol levels. No serious side-effects were found. We conclude that both dosages of TU can effectively, safely, and reversibly suppress spermatogenesis in normal Chinese men.
Endocr Rev. 2008 Jun;29(4):465-93. Epub 2008 Apr 24.
Page ST, Amory JK, Bremner WJ.
Center for Research in Reproduction and Contraception, Department of Medicine, University of Washington School of Medicine, Seattle, Washington 98195, USA. firstname.lastname@example.org
Despite significant advances in contraceptive options for women over the last 50 yr, world population continues to grow rapidly. Scientists and activists alike point to the devastating environmental impacts that population pressures have caused, including global warming from the developed world and hunger and disease in less developed areas. Moreover, almost half of all pregnancies are still unwanted or unplanned. Clearly, there is a need for expanded, reversible, contraceptive options. Multicultural surveys demonstrate the willingness of men to participate in contraception and their female partners to trust them to do so. Notwithstanding their paucity of options, male methods including vasectomy and condoms account for almost one third of contraceptive use in the United States and other countries. Recent international clinical research efforts have demonstrated high efficacy rates (90-95%) for hormonally based male contraceptives. Current barriers to expanded use include limited delivery methods and perceived regulatory obstacles, which stymie introduction to the marketplace. However, advances in oral and injectable androgen delivery are cause for optimism that these hurdles may be overcome. Nonhormonal methods, such as compounds that target sperm motility, are attractive in their theoretical promise of specificity for the reproductive tract. Gene and protein array technologies continue to identify potential targets for this approach. Such nonhormonal agents will likely reach clinical trials in the near future. Great strides have been made in understanding male reproductive physiology; the combined efforts of scientists, clinicians, industry and governmental funding agencies could make an effective, reversible, male contraceptive an option for family planning over the next decade.