ObjectivesThe aim of the study was to characterize contemporary patterns and correlates of testosterone therapy (TTh) use and discontinuation by HIV serostatus among men in the Multicenter AIDS Cohort Study (MACS). MethodsSelf-reported testosterone use data were collected semiannually from 2400 (1286 HIV-infected and 1114 HIV-uninfected) men who have sex with men. Multivariable Poisson regression was used to estimate prevalence ratios for TTh use and predictors of TTh discontinuation (2012-2015). ResultsUse was higher among HIV-infected compared with HIV-uninfected men in all age strata, with an age-adjusted prevalence of 17% vs. 5%, respectively (adjusted prevalence ratio 3.7; P < 0.001). Correlates of use in the multivariable model were similar by HIV serostatus: white race, the Los Angeles (LA) site, more than one recent sexual partner, non-smoking status, and higher American Heart Association/American College of Cardiology (AHA/ACC) cardiovascular disease (CVD) risk score category (approximately 70% of testosterone users were in the high-risk category). Compared with HIV-uninfected men, HIV-infected men more frequently reported building muscle mass as a motivation for testosterone use. The TTh discontinuation rate was 20.9/100 person-years [95% confidence interval (CI) 17.3, 25.0/100 person-years]. Relative to HIV-uninfected men, HIV-infected men were half as likely to discontinue (adjusted incidence rate ratio 0.4; P < 0.001). Discontinuation was 40% higher in the period after the US Food and Drug Administration (FDA) safety communication for testosterone in 2014, independent of co-factors (P = 0.06). ConclusionsGiven the high prevalence of both TTh use and CVD risk among HIV-infected men, the benefits and risks of TTh should be examined in future studies of aging HIV-infected men and monitored routinely in clinical practice.

Aging is a multifactorial process that is associated with a progressive decline of multiple organ systems, leading to chronic disease, disability, and eventually death. The universal dream of humans is to live as long and healthy as possible. However, aging mechanism(s) are not clearly understood, making it difficult to develop anti-aging interventions. Several theories have been proposed to explain the inevitability of aging such as DNA damage, protein aggregation and misfolding, alteration in Ca++ signaling, accumulation of oxidative stress, apoptosis, and alteration in mitochondrial permeability.1 All these mechanisms have been targeted for designing anti-aging interventions. This CAM Corner will briefly review some proposed anti-aging interventions including calorie restriction, drugs, antioxidant supplements, specific foods, and vitamins. Language: en

Context: In the absence of panhypopituitarism and low serum IGF-I levels, the diagnosis of adult GH deficiency (AGHD) requires confirmation with a GH stimulation test. Macimorelin is a novel, orally active ghrelin mimetic that stimulates GH secretion.Objective: The objective of the study was to determine the diagnostic efficacy and safety of macimorelin in AGHD.Design: This was a multicenter open-label study comparing the diagnostic accuracy of oral macimorelin with that of arginine+GHRH in AGHD patients and healthy, matched controls. After 43 AGHD patients and 10 controls were tested, the GHRH analog Geref Diagnostic [GHRH(1-29) NH2] became unavailable in the United States. The study was completed by testing 10 additional AGHD patients and 38 controls with macimorelin alone.Main Outcome Measure: Peak GH area under the receiver operating characteristic curve after macimorelin was measured.Results: Fifty AGHD subjects and 48 controls were evaluated. Peak GH levels in AGHD patients and controls after macimorelin were 2.36 +/- 5.69 and 17.71 +/- 19.11 ng/mL, respectively (P < .0001). With macimorelin, the receiver operating characteristic analysis yielded an optimal GH cut point of 2.7 ng/mL, with82% sensitivity, 92% specificity, and13% misclassification rate. For subjects receiving both tests, macimorelin showed discrimination comparable with arginine+GHRH (area under the receiver operating characteristic curve 0.99 vs 0.94, respectively, P = .29). Obesity (body mass index > 30 kg/m(2)) was present in 58% of subjects, and peak GH levels were inversely associated with body mass index in controls (r = -0.37, P = .01). Using the separate cut points of 6.8 ng/mL for nonobese and 2.7 for obese subjects reduced the misclassification rate to 11%. Only 1 drug-related serious adverse event, an asymptomatic QT interval prolongation on the electrocardiogram, was reported.Conclusion: Oral macimorelin is safe, convenient, and effective in diagnosing AGHD with accuracy comparable with the arginine+GHRH test.

Purpose of review To review recent data concerning the relationship between endogenous testosterone and lipids as well as testosterone replacement therapy and lipids. To describe the effects of sex hormones on cardiovascular disease (CVD) that may act via serum lipids. Recent findings Low endogenous testosterone is associated with high low-density lipoprotein and low high-density lipoprotein in both cross-sectional and prospective observational studies. Exogenous testosterone administration is associated with decreased high-density lipoprotein coupled with beneficial decreases in low-density lipoprotein and total cholesterol. The overall impact of testosterone administration on CVD is still unclear, with mixed safety results from recent randomized controlled trials. Summary There may be CVD risk reduction benefits, including an improved lipid profile, from testosterone administration in hypogonadal men. The overall effect of testosterone on CVD risk has not been definitively determined.

Low or high hematocrit levels are associated with increased morbidity and mortality, mediated via anemia or thromboembolic events, respectively. It is therefore important to identify factors that influence hematocrit. Although androgens are known to stimulate hematopoietic cells, it is unknown whether circulating sex steroid hormones affect hematocrit. The association between serum sex steroid hormone concentrations and hematocrit in men aged ≥ 20 years was evaluated in a cross-sectional study of 1273 men in the Third National Health and Nutrition Examination Survey (1988-1991). Outcomes were low (<10th percentile), high (>90th percentile), and mean hematocrit. Men with low free testosterone levels had a lower hematocrit than men with normal free testosterone levels (P = .03), although no relationship was found between total testosterone level and hematocrit. The relationship between sex hormone-binding globulin (SHBG) and hematocrit was complex, with both low (P < .001) and high (P = .01) SHBG levels associated with lower hematocrit in men aged ≥ 20 years and only high (P = .01) SHBG levels in men aged ≥ 50 years. The odds ratio (OR) of high vs normal hematocrit increased as total estradiol (OR, 2.84; P trend = .04) and free estradiol (OR, 2.23; P trend = .09) levels increased. In this nationally representative study of men, sex steroid hormone levels, particularly low free testosterone and high SHBG levels, were associated with lower hematocrit, and high total and free estradiol levels were associated with high hematocrit. Thus, changes in sex hormone levels with aging may contribute to the increased prevalence of anemia and thromboembolic stroke in men as they age.

OBJECTIVE: Waist-to-hip ratio (WHR) is strongly associated with prevalent atherosclerosis. We analyzed the associations of baseline serum levels of testosterone (T), estradiol (E2), sex-hormone-binding globulin (SHBG) and dehydroepiandrosterone (DHEA) with WHR in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. SUBJECTS: Baseline data was available for 3144 men and 2038 postmenopausal women, who were non-users of hormone therapy, who were 45–84 years of age, and of White, Chinese, Black or Hispanic racial/ethnic groups. Of these, 2708 men and 1678 women also had longitudinal measurements of WHR measured at the second and/or the third study visits (median follow-up 578 days and 1135 days, respectively). RESULTS: In cross-sectional analyses adjusted for age, race and cardiovascular disease risk factors, T was negatively associated with baseline WHR in men, whereas in both sexes, E2 was positively associated and SHBG was negatively associated with WHR (all P <0.001). In longitudinal analyses, further adjusted for follow-up time and baseline WHR, baseline T was negatively associated with WHR at follow-up ( P =0.001) in men, whereas in both sexes, E2 was positively associated ( P =0.004) and SHBG was negatively associated with WHR ( P <0.001). The longitudinal association of E2, but not T, was independent of SHBG. In cross-sectional or longitudinal analyses, there were no associations between DHEA and WHR in either men or women. CONCLUSION: Sex hormones are associated with WHR at baseline and also during follow-up above and beyond their baseline association. Future research is needed to determine if manipulation of hormones is associated with changes in central obesity.

ObjectiveThe aim of the study was to describe longitudinal changes in serum lipids among HIV-infected men receiving highly active antiretroviral therapy (HAART) with long-term follow-up.MethodsA total of 304 HIV-infected men who initiated HAART and who had serum lipid measurements prior to and for up to 7 years after HAART initiation were identified from the Multicenter AIDS Cohort Study (MACS). Mean levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were examined at biannual time-points.ResultsSignificant lipid changes were seen within 0.5 years of HAART initiation but increases in TC (+1.09 mmol/L), LDL-C (+0.57 mmol/L), HDL-C (+0.16 mmol/L) and non-HDL-C (+0.91 mmol/L) reached peak levels 2-3 years after HAART initiation. Declines in serum TC, LDL-C and non-HDL-C in subsequent years occurred concurrently with a substantial increase in use of lipid-lowering medications (from 1% usage pre-HAART to 43% 6-7 years after HAART initiation) but the proportion of men who either were treated with cholesterol-lowering medication or had elevated cholesterol levels (> 5.18 mmol/L) did not change during the 2-7-year interval after HAART. Mean HDL-C also decreased after 2-3 years and was low (< 1.04 mmol/L) in 55% of HIV-infected men 6-7 years after HAART initiation.ConclusionsAtherogenic serum lipids increased early after the initiation of HAART, peaked at 2-3 years and remained high or required treatment thereafter. Low HDL-C levels persisted in the majority of men. The long-term effects of lipid abnormalities on cardiovascular risk and the effectiveness and toxicity of prolonged use of lipid-lowering medications in combination with HAART are not known.

HomeCirculationVol. 116, No. 23Testosterone Making an Entry Into the Cardiometabolic World Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBTestosterone Making an Entry Into the Cardiometabolic World Shehzad Basaria and Adrian S. Dobs Shehzad BasariaShehzad Basaria From the Division of Endocrinology & Metabolism, The Johns Hopkins University School of Medicine, Baltimore, Md. Search for more papers by this author and Adrian S. DobsAdrian S. Dobs From the Division of Endocrinology & Metabolism, The Johns Hopkins University School of Medicine, Baltimore, Md. Search for more papers by this author Originally published4 Dec 2007https://doi.org/10.1161/CIRCULATIONAHA.107.740365Circulation. 2007;116:2658–2661Testosterone, the predominant sex hormone in men, is produced by the testes under stimulation by the gonadotrophs in the pituitary, which in turn are controlled by gonadotropin-releasing hormone neurons in the hypothalamus. A young adult man generally produces 3 to 10 mg of testosterone daily, which translates into serum values of 300 to 1000 ng/dL. The consequences of classical male hypogonadism (primary or secondary) have been long known to physicians and patients alike and include decreased libido, erectile dysfunction, osteoporosis, reduced sexual hair, and changes in body habitus. Recently, we have come to appreciate that reductions in serum testosterone resulting from aging or chronic disease have signs and symptoms similar to those seen in classical male hypogonadism, along with increased fat mass, decreased lean body mass, decreased muscle strength, and diminished quality of life.1 During the past decade, reports have been trickling in, mainly from laboratory and epidemiological studies (and a few clinical studies), linking differences in serum testosterone levels to various cardiovascular risk factors and also directly to cardiovascular disease and death. The article by Khaw et al2 in this issue of Circulation is another link to this growing chain.Article p 2694Thirteen years ago, Phillips et al3 reported that low total and free testosterone levels were inversely linked to coronary artery disease, even after adjusting for age and adiposity. This observation still holds true, as was recently supported by a study showing that men with angiographically proven coronary artery disease had lower levels of testosterone than those of controls.4 Furthermore, testosterone levels were negatively correlated to the degree of coronary involvement. A few population-based studies have been published that relate low serum testosterone level with risk of death. A study of male veterans showed that low testosterone was associated with increased risk of death5; however, it was a retrospective study, and the subjects were a clinic-based Veterans Administration population, who tend to have greater medical morbidity, rather than healthy men living in the community. Recently, a prospective population-based study of 794 men, 50 to 91 years of age, in the Rancho Bernardo community, looked at the relationship of testosterone with all-cause death over the subsequent 2 decades.6 The authors found that men whose total testosterone levels were in the lowest quartile, defined as <241 ng/dL, were 40% more likely to die than were men with higher androgen levels. These findings were independent of age, adiposity, lipids, adipokines, and lifestyle. In cause-specific analyses, low testosterone predicted increased risk of death due to cardiovascular and respiratory disease. The findings of this study are not surprising given the fact that low testosterone is independently associated with many of the individual risk factors for heart disease. For example, testosterone levels are inversely related to fat mass in men.7 Indeed, men undergoing androgen deprivation for the treatment of prostate cancer have higher body mass index and fat mass than age and disease-matched controls.8 This role of fat mass regulation by androgens is further supported by the fact that testosterone administration decreases adiposity in men.9 Because fat mass is an independent predictor of cardiovascular death, it seems that testosterone is an important player in regulating this cardiovascular risk.In addition to body mass index and fat mass, testosterone has been linked to other cardiovascular risk factors. The vascular system seems to be an important target of androgen action, and current evidence suggests that androgens are beneficial to the vascular system. Older clinical trials, though not as rigorously conducted, showed that testosterone replacement relieved symptoms of angina and peripheral vascular disease.10 Almost half a century later, experimental studies showed that acute treatment with testosterone results in dilatation of the coronary arteries in animals.11 Subsequently, a clinical trial showed that transdermal testosterone therapy improved exercise-induced myocardial ischemia (measured as time to ST depression) during an exercise stress test in men with stable angina.12 These vasodilatory effects of testosterone on coronary and other vasculature are confirmed by the findings that men with prostate cancer undergoing androgen-deprivation therapy experience an increase in central arterial pressure (reflecting stiffening of large arteries).13 Similarly, in population studies, systolic and diastolic blood pressures have been shown to be inversely correlated with testosterone level.14In addition to vasomotor regulation, testosterone levels are also inversely related with arterial calcification. In the Rotterdam Study, the association between total and bioavailable testosterone with aortic atherosclerosis was evaluated in 504 nonsmoking men ≥55 years of age.15 Compared with men with levels of total and bioavailable testosterone in the lowest tertile, men in the highest tertile had a risk reduction of 60% to 80% of severe aortic atherosclerosis. Adjustments for age and cardiovascular risk factors did not influence these results. Given that aortic atherosclerosis was assessed by radiographic detection of calcification in the abdominal aorta, it is likely that subclinical atherosclerosis was not detected in this study. Another prospective study of elderly men (mean age 77 years) showed free testosterone concentration to be inversely related to the progression of intima-media thickness of the common carotid artery after adjustment for age and other risk factors.16 Hence, it appears that arterial stiffening and increased atherosclerosis are 2 mechanisms by which male hypogonadism may contribute to high risk of death.Another mechanism by which low testosterone may contribute to a higher death rate is its association with diabetes. Epidemiological studies show that low testosterone levels are independently associated with type 2 diabetes mellitus after adjusting for potential confounders.17 In fact, lower concentrations of free and bioavailable testosterone even in the normal range are associated with diabetes, independent of adiposity.18 Furthermore, low total testosterone levels independently predict development of the metabolic syndrome in middle-aged men.19 A clinical model that further establishes the role of testosterone in the mediation of glucose metabolism is that of androgen deprivation in men with prostate cancer. It is seen that insulin resistance develops within a few months of initiation of androgen-deprivation therapy13; however, when men undergoing long-term androgen deprivation are studied, in addition to hyperinsulinemia, they have a higher prevalence of hyperglycemia and metabolic syndrome.20,21 This relationship between hypogonadism and hyperglycemia persists even after adjustment for age and body mass index, and the degree of hyperglycemia is directly related to the duration of sex hormone suppression.22 Thus, hypoandrogenism seems to be an early marker for disturbances in insulin and glucose metabolism and may contribute to the pathogenesis of diabetes and metabolic syndrome, thus again contributing to the cardiovascular risk.Another risk factor linking hypogonadism to cardiovascular disease is the association of androgens with lipids and inflammatory cytokines. Epidemiological data suggest that testosterone levels are associated with a beneficial lipid profile, with negative correlations with total cholesterol, low-density lipoprotein cholesterol, and triglycerides and a positive association with high-density lipoprotein cholesterol.23 Similarly, there are reports of inverse associations between inflammatory cytokines and testosterone.24 These associations are further validated by clinical trials showing improvement in lipid profile and reduction in inflammatory cytokines with testosterone replacement.25 Additionally, inverse associations between testosterone and plasminogen activator inhibitor I, fibrinogen, and factor VII have been reported in men.15 Animal experiments also suggest beneficial effects of testosterone on plaque development.26 In summary, these findings suggest that testosterone may influence cardiovascular disease via multiple mechanisms, including changes in body composition, fat metabolism, glucose regulation, vascular mechanisms, and clotting (see the Figure). Download figureDownload PowerPointFigure. Potential cardiovascular risk factors associated with male hypogonadism.In this issue of Circulation, Khaw et al2 provide more evidence that makes the chain linking low testosterone to risk of death even stronger.2 The authors conducted a nested case–control study to determine the association of endogenous serum testosterone with all-cause, cardiovascular, and cancer-related death. The authors compared 825 men, who did not have any cardiovascular disease or cancer at baseline but died during the course of follow-up, with 1489 men who were still alive. The cases and controls were matched for age and date of baseline visit. The authors found that baseline testosterone levels were inversely related to deaths due to all causes, cardiovascular disease, and malignancy, after controlling for the usual confounders (plus dehydroepiandrosterone sulfate and sex hormone–binding globulin). This protective effect of testosterone increased with increasing quartiles, such that men in the highest quartile had a 30% lower risk of death than that of those in the lowest quartile. Even after excluding deaths during the first 2 years of follow-up, this inverse relationship was maintained. In fact, every 6-nmol/L (173-ng/dL) increase in serum testosterone decreased the death rate by 14%, and this benefit was irrespective of patient’s age (above or below 65 years of age).Though the study was well conducted, the findings should be interpreted with caution. First, the testosterone values were based on only a single measurement. Hence, one cannot control for any errors in measurement or transient variation in testosterone secretion. Second, the authors did not measure or calculate either free or bioavailable testosterone, the moiety that binds to the androgen receptor. These measures are more accurate than total testosterone, especially in subjects with obesity or diabetes and in older men because changes in sex hormone–binding globulin levels are expected in such patients. Finally, the authors did not measure estradiol levels. It would have been interesting to see whether these beneficial effects of testosterone are mediated by the testosterone itself or via aromatization to estradiol.So is low serum testosterone just a marker for sickness (or wellness), or does it have a true pathogenic role? Even though Khaw et al2 excluded men with serious disease and also those who died within the first 2 years of baseline visit (assuming that they may have had subclinical illness), the authors were cautious enough (rightly so) in mentioning that they still might have included men with subclinical disease. Nevertheless, on the basis of all the evidence cited in the present editorial, we believe that testosterone has a pathogenic role in the development of cardiovascular disease and is not simply a “marker” for illness and wellness. In terms of death related to cancer and respiratory disease (an association suggested by other reports),27 the exact mechanism by which testosterone may cause an increased risk of death is currently unknown.Hence, increasing evidence indicates that low androgen levels are associated with all-cause death and especially cardiovascular death. What do we do now on the basis of the reasonably substantial information discussed with regard to testosterone and cardiovascular disease? We believe the answer lies in long-term, double-blind, randomized, placebo-controlled trials of androgen replacement in men with low testosterone levels to evaluate its effects on cardiovascular disease, cardiovascular death, and all-cause death. We cannot assume that testosterone replacement will ameliorate the increased risk seen in these epidemiological studies. We still have not answered questions about the critical level for starting treatment, optimal dose, target testosterone level to be reached, or long-term safety. What we need is a Men’s Health Initiative study. With all these data, androgens should no longer be considered as mediators of only sexual function or skeletal health, nor should they be discarded by defaming them as a “fountain of youth,” as has been done by some critics of androgen replacement. The aim is to critically evaluate the effects of testosterone treatment by performing large trials, similar to those recently performed in women, and not just to prevent a man from going through the last 2 stages of life (old age and dementia) as described by Shakespeare in the “Seven Ages of Man.” A few years ago, the Institute of Medicine did not recommend funding for such a large study. It appears that, in light of emerging evidence, the Institute may act differently if approached again.The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.DisclosuresBoth authors have received research funding from Solvay Pharmaceuticals.FootnotesCorrespondence to Adrian S. Dobs, MD, MHS, Division of Endocrinology & Metabolism, Johns Hopkins University School of Medicine, 1830 E Monument St, Suite 328, Baltimore, MD 21287. E-mail [email protected] References 1 Basaria S, Dobs AS. Hypogonadism and androgen replacement therapy in elderly men. Am J Med. 2001; 110: 563–572.CrossrefMedlineGoogle Scholar2 Khaw K-T, Dowsett M, Folkerd E, Bingham S, Wareham N, Luben R, Welch A, Day N. Endogenous testosterone and mortality due to all causes, cardiovascular disease, and cancer in men: European Prospective Investigation Into Cancer in Norfolk (EPIC-Norfolk) Prospective Population Study. Circulation. 2007; 116: 2694–2701.LinkGoogle Scholar3 Phillips GB, Pinkernell BH, Jing TY. The association of hypotestosteronemia with coronary artery disease in men. Arterioscler Thromb. 1994; 14: 701–706.CrossrefMedlineGoogle Scholar4 Rosano GM, Sheiban I, Massaro R, Pagnotta P, Marazzi G, Vitale C, Mercuro G, Volterrani M, Aversa A, Fini M. Low testosterone levels are associated with coronary artery disease in male patients with angina. Int J Impot Res. 2007; 19: 176–182.CrossrefMedlineGoogle Scholar5 Shores MM, Matsumoto AM, Sloan KL, Kivlahan DR. Low serum testosterone and mortality in male veterans. Arch Intern Med. 2006; 166: 1660–1665.CrossrefMedlineGoogle Scholar6 Laughlin GA, Barrett-Connor E, Bergstrom J. Low serum testosterone and mortality in older men. J Clin Endocrinol Metab. Published before print October 2, 2007. DOI: 10.1210/jc.2007-1792. Available at: http://jcem.endojournals.org. Accessed November 13, 2007.Google Scholar7 van den Beld AW, de Jong FH, Grobbee DE, Pols HA, Lamberts SW. Measures of bioavailable serum testosterone and estradiol and their relationships with muscle strength, bone density, and body composition in elderly men. J Clin Endocrinol Metab. 2000; 85: 3276–3282.MedlineGoogle Scholar8 Basaria S, Lieb J 2nd, Tang AM, DeWeese T, Carducci M, Eisenberger M, Dobs AS. Long-term effects of androgen deprivation therapy in prostate cancer patients. Clin Endocrinol (Oxf). 2002; 56: 779–786.CrossrefMedlineGoogle Scholar9 Snyder PJ, Peachey H, Hannoush P, Berlin JA, Loh L, Lenrow DA, Holmes JH, Dlewati A, Santanna J, Rosen CJ, Strom BL. Effect of testosterone treatment on body composition and muscle strength in men over 65 years of age. J Clin Endocrinol Metab. 1999; 84: 2647–2653.MedlineGoogle Scholar10 Lesser MA. Testosterone propionate therapy in one hundred cases of angina pectoris. J Clin Endocrinol Metab. 1946; 6: 549–557.CrossrefMedlineGoogle Scholar11 Chou TM, Sudhir K, Hutchison SJ, Ko E, Amidon TM, Collins P, Chatterjee K. Testosterone induces dilation of canine coronary conductance and resistance arteries in vivo. Circulation. 1996; 94: 2614–2619.CrossrefMedlineGoogle Scholar12 English KM, Steeds RP, Jones TH, Diver MJ, Channer KS. Low-dose transdermal testosterone therapy improves angina threshold in men with chronic stable angina: a randomized, double-blind, placebo-controlled study. Circulation. 2000; 102: 1906–1911.CrossrefMedlineGoogle Scholar13 Smith JC, Bennett S, Evans LM, Kynaston HG, Parmar M, Mason MD, Cockcroft JR, Scanlon MF, Davies JS. The effects of induced hypogonadism on arterial stiffness, body composition, and metabolic parameters in males with prostate cancer. J Clin Endocrinol Metab. 2001; 86: 4261–4267.CrossrefMedlineGoogle Scholar14 Khaw KT, Barrett-Connor E. Blood pressure and endogenous testosterone in men: an inverse relationship. J Hypertens. 1988; 6: 329–332.CrossrefMedlineGoogle Scholar15 Hak AE, Witteman JC, de Jong FH, Geerlings MI, Hofman A, Pols HA. Low levels of endogenous androgens increase the risk of atherosclerosis in elderly men: the Rotterdam study. J Clin Endocrinol Metab. 2002; 87: 3632–3639.CrossrefMedlineGoogle Scholar16 Muller M, van den Beld AW, Bots ML, Grobbee DE, Lamberts SW, van der Schouw YT. Endogenous sex hormones and progression of carotid atherosclerosis in elderly men. Circulation. 2004; 109: 2074–2079.LinkGoogle Scholar17 Stellato RK, Feldman HA, Hamdy O, Horton ES, McKinlay JB. Testosterone, sex hormone-binding globulin, and the development of type 2 diabetes in middle-aged men: prospective results from the Massachusetts male aging study. Diabetes Care. 2000; 23: 490–494.CrossrefMedlineGoogle Scholar18 Selvin E, Feinleib M, Zhang L, Rohrmann S, Rifai N, Nelson WG, Dobs A, Basaria S, Golden SH, Platz EA. Androgens and diabetes in men: results from the Third National Health and Nutrition Examination Survey (NHANES III). Diabetes Care. 2007; 30: 234–238.CrossrefMedlineGoogle Scholar19 Laaksonen DE, Niskanen L, Punnonen K, Nyyssonen K, Tuomainen TP, Valkonen VP, Salonen R, Salonen JT. Testosterone and sex hormone–binding globulin predict the metabolic syndrome and diabetes in middle-aged men. Diabetes Care. 2004; 27: 1036–1041.CrossrefMedlineGoogle Scholar20 Basaria S, Muller DC, Carducci MA, Egan J, Dobs AS. Hyperglycemia and insulin resistance in men with prostate carcinoma who receive androgen-deprivation therapy. Cancer. 2006; 106: 581–588.CrossrefMedlineGoogle Scholar21 Braga-Basaria M, Dobs AS, Muller DC, Carducci MA, John M, Egan J, Basaria S. Metabolic syndrome in men with prostate cancer undergoing long-term androgen-deprivation therapy. J Clin Oncol. 2006; 24: 3979–3983.CrossrefMedlineGoogle Scholar22 Basaria S, Muller DC, Carducci MA, Egan J, Dobs AS. Relation between duration of androgen deprivation therapy and degree of insulin resistance in men with prostate cancer. Arch Intern Med. 2007; 167: 612–613.CrossrefMedlineGoogle Scholar23 Haffner SM, Mykkanen L, Valdez RA, Katz MS. Relationship of sex hormones to lipids and lipoproteins in nondiabetic men. J Clin Endocrinol Metab. 1993; 77: 1610–1615.MedlineGoogle Scholar24 Maggio M, Basaria S, Ble A, Lauretani F, Bandinelli S, Ceda GP, Valenti G, Ling SM, Ferrucci L. Correlation between testosterone and the inflammatory marker soluble interleukin-6 receptor in older men. J Clin Endocrinol Metab. 2006; 91: 345–347.CrossrefMedlineGoogle Scholar25 Malkin CJ, Pugh PJ, Jones RD, Kapoor D, Channer KS, Jones TH. The effect of testosterone replacement on endogenous inflammatory cytokines and lipid profiles in hypogonadal men. J Clin Endocrinol Metab. 2004; 89: 3313–3318.CrossrefMedlineGoogle Scholar26 Hanke H, Lenz C, Hess B, Spindler KD, Weidemann W. Effect of testosterone on plaque development and androgen receptor expression in the arterial vessel wall. Circulation. 2001; 103: 1382–1385.CrossrefMedlineGoogle Scholar27 Araujo AB, Kupelian V, Page ST, Handelsman DJ, Bremner WJ, McKinlay JB. Sex steroids and all-cause and cause-specific mortality in men. Arch Intern Med. 2007; 167: 1252–1260.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Braga-Basaria M, Travison T, Taplin M, Lin A, Dufour A, Habtemariam D, Nguyen P, Kibel A, Ravi P, Bearup R, Kackley H, Kafel H, Reid K, Storer T, Simonson D, McDonnell M, Basaria S and Ummarino D (2023) Gaining metabolic insight in older men undergoing androgen deprivation therapy for prostate cancer (the ADT & Metabolism Study): Protocol of a longitudinal, observational, cohort study, PLOS ONE, 10.1371/journal.pone.0281508, 18:2, (e0281508) Gencer B, Bonomi M, Adorni M, Sirtori C, Mach F and Ruscica M (2021) Cardiovascular risk and testosterone – from subclinical atherosclerosis to lipoprotein function to heart failure, Reviews in Endocrine and Metabolic Disorders, 10.1007/s11154-021-09628-2, 22:2, (257-274), Online publication date: 1-Jun-2021. Traish A (2017) Negative Impact of Testosterone Deficiency and 5α-Reductase Inhibitors Therapy on Metabolic and Sexual Function in Men Sex and Gender Factors Affecting Metabolic Homeostasis, Diabetes and Obesity, 10.1007/978-3-319-70178-3_22, (473-526), . Dehlendorff C, Andersen K and Olsen T (2015) Sex Disparities in Stroke: Women Have More Severe Strokes but Better Survival Than Men, Journal of the American Heart Association, 4:7, Online publication date: 17-Jul-2015. Bello A, Stenvinkel P, Lin M, Hemmelgarn B, Thadhani R, Klarenbach S, Chan C, Zimmerman D, Cembrowski G, Strippoli G, Carrero J and Tonelli M (2014) Serum Testosterone Levels and Clinical Outcomes in Male Hemodialysis Patients, American Journal of Kidney Diseases, 10.1053/j.ajkd.2013.06.010, 63:2, (268-275), Online publication date: 1-Feb-2014. Vlachopoulos C, Terentes-Printzios D, Ioakeimidis N, Aznaouridis K and Stefanadis C (2013) Prediction of Cardiovascular Events and All-Cause Mortality With Erectile Dysfunction, Circulation: Cardiovascular Quality and Outcomes, 6:1, (99-109), Online publication date: 1-Jan-2013. Maggio M, Nicolini F, Cattabiani C, Beghi C, Gherli T, Schwartz R, Valenti G and Ceda G (2012) Effects of testosterone supplementation on clinical and rehabilitative outcomes in older men undergoing on-pump CABG, Contemporary Clinical Trials, 10.1016/j.cct.2012.02.019, 33:4, (730-738), Online publication date: 1-Jul-2012. Torkler S, Wallaschofski H, Baumeister S, Völzke H, Dörr M, Felix S, Rettig R, Nauck M and Haring R (2010) Inverse association between total testosterone concentrations, incident hypertension and blood pressure, The Aging Male, 10.3109/13685538.2010.529194, 14:3, (176-182), Online publication date: 1-Sep-2011. Yilmaz M, Sonmez A, Qureshi A, Saglam M, Stenvinkel P, Yaman H, Eyileten T, Caglar K, Oguz Y, Taslipinar A, Vural A, Gok M, Unal H, Yenicesu M and Carrero J (2011) Endogenous Testosterone, Endothelial Dysfunction, and Cardiovascular Events in Men with Nondialysis Chronic Kidney Disease, Clinical Journal of the American Society of Nephrology, 10.2215/CJN.10681210, 6:7, (1617-1625), Online publication date: 1-Jul-2011. Traish A and Kypreos K (2011) Testosterone and cardiovascular disease: An old idea with modern clinical implications, Atherosclerosis, 10.1016/j.atherosclerosis.2010.08.078, 214:2, (244-248), Online publication date: 1-Feb-2011. Abdel‐Rahman M (2010) Influence of dietary fat on renal function, lipid profile, sex hormones, and electrolyte balance in rats, European Journal of Lipid Science and Technology, 10.1002/ejlt.200900297, 112:10, (1166-1172), Online publication date: 1-Oct-2010. Moreno-Pérez O, Escoín C, Serna-Candel C, Portilla J, Boix V, Alfayate R, González-Sánchez V, Mauri M, Sánchez-Payá J and Picó A (2010) The Determination of Total Testosterone and Free Testosterone (RIA) are not Applicable to the Evaluation of Gonadal Function in HIV-Infected Males, The Journal of Sexual Medicine, 10.1111/j.1743-6109.2010.01886.x, 7:8, (2873-2883), Online publication date: 1-Aug-2010. Olsen T and Andersen K (2010) Female survival advantage relates to male inferiority rather than female superiority: A hypothesis based on the impact of age and stroke severity on 1-week to 1-year case fatality in 40,155 men and women, Gender Medicine, 10.1016/j.genm.2010.08.001, 7:4, (284-295), Online publication date: 1-Aug-2010. Corona G, Monami M, Boddi V, Balzi D, Melani C, Federico N, Balzi D, Sforza A, Rotella C, Forti G, Mannucci E and Maggi M (2010) Is Obesity a Further Cardiovascular Risk Factor in Patients with Erectile Dysfunction?, The Journal of Sexual Medicine, 10.1111/j.1743-6109.2010.01839.x, 7:7, (2538-2546), Online publication date: 1-Jul-2010. Jackson G (2010) Testosterone deficiency syndrome (TDS) and the heart, European Heart Journal, 10.1093/eurheartj/ehq096, 31:12, (1436-1437), Online publication date: 2-Jun-2010. Haring R, Volzke H, Steveling A, Krebs A, Felix S, Schofl C, Dorr M, Nauck M and Wallaschofski H (2010) Low serum testosterone levels are associated with increased risk of mortality in a population-based cohort of men aged 20-79, European Heart Journal, 10.1093/eurheartj/ehq009, 31:12, (1494-1501), Online publication date: 2-Jun-2010. Jackson G, Boon N, Eardley I, Kirby M, Dean J, Hackett G, Montorsi P, Montorsi F, Vlachopoulos C, Kloner R, Sharlip I and Miner M (2010) Erectile dysfunction and coronary artery disease prediction: evidence-based guidance and consensus, International Journal of Clinical Practice, 10.1111/j.1742-1241.2010.02410.x, 64:7, (848-857) Corona G, Monami M, Boddi V, Cameron-Smith M, Fisher A, De Vita G, Melani C, Balzi D, Sforza A, Forti G, Mannucci E and Maggi M (2010) Low Testosterone is Associated with an Increased Risk of MACE Lethality in Subjects with Erectile Dysfunction, The Journal of Sexual Medicine, 10.1111/j.1743-6109.2009.01690.x, 7:4, (1557-1564), Online publication date: 1-Apr-2010. Traish A, Abdou R and Kypreos K (2009) Androgen deficiency and atherosclerosis: The lipid link, Vascular Pharmacology, 10.1016/j.vph.2009.09.003, 51:5-6, (303-313), Online publication date: 1-Nov-2009. Yi S, Selvin E, Rohrmann S, Basaria S, Menke A, Rifai N, Guallar E, Platz E and Astor B (2009) Endogenous sex steroid hormones and measures of chronic kidney disease (CKD) in a nationally representative sample of men, Clinical Endocrinology, 10.1111/j.1365-2265.2008.03455.x, 71:2, (246-252), Online publication date: 1-Aug-2009. Archer J and Baker E (2009) Diabetes and metabolic dysfunction in COPD, Respiratory Medicine: COPD Update, 10.1016/j.rmedu.2009.10.001, 5:3-4, (67-74), Online publication date: 1-Aug-2009. Tivesten A, Vandenput L, Labrie F, Karlsson M, Ljunggren O, Mellström D and Ohlsson C (2009) Low Serum Testosterone and Estradiol Predict Mortality in Elderly Men, The Journal of Clinical Endocrinology & Metabolism, 10.1210/jc.2008-2650, 94:7, (2482-2488), Online publication date: 1-Jul-2009. Moreno-Pérez O, Picó Alfonso A and Portilla J (2009) Hipogonadismo, disfunción eréctil y disfunción endotelial en varones con infección por el virus de la inmunodeficiencia humana, Medicina Clínica, 10.1016/j.medcli.2008.07.018, 132:8, (311-321), Online publication date: 1-Mar-2009. Newton T (2009) Cardiovascular functioning, personality, and the social world: The domain of hierarchical power, Neuroscience & Biobehavioral Reviews, 10.1016/j.neubiorev.2008.07.005, 33:2, (145-159), Online publication date: 1-Feb-2009. Er F, Gassanov N, Brandt M, Madershahian N and Hoppe U (2009) Impact of Dihydrotestosterone on L-Type Calcium Channels in Human Ventricular Cardiomyocytes, Endocrine Research, 10.1080/07435800903136953, 34:3, (59-67), Online publication date: 1-Jan-2009. Jackson G (2008) Cardiovascular effects of testosterone, Current Sexual Health Reports, 10.1007/s11930-008-0033-6, 5:4, (187-189), Online publication date: 1-Dec-2008. Jackson G (2008) Testosterone reducing cardiovascular risk - looks promising but randomised trials needed, International Journal of Clinical Practice, 10.1111/j.1742-1241.2008.01839.x, 62:8, (1131-1132) Potenza M and Shimshi M (2008) Male hypogonadism: The unrecognized cardiovascular risk factor, Journal of Clinical Lipidology, 10.1016/j.jacl.2008.01.011, 2:2, (71-78), Online publication date: 1-Apr-2008. December 4, 2007Vol 116, Issue 23 Advertisement Article InformationMetrics https://doi.org/10.1161/CIRCULATIONAHA.107.740365PMID: 18056536 Originally publishedDecember 4, 2007 KeywordsEditorialshormonesepidemiologymentestosteronePDF download Advertisement SubjectsEpidemiology

The Journal of Alternative and Complementary MedicineVol. 13, No. 3 Letters to the EditorClinicians' Attitudes and Usage of Complementary and Alternative Integrative Medicine: A Survey at The Johns Hopkins Medical InstituteMi-Yeon Song, Majnu John, and Adrian S. DobsMi-Yeon Song, Majnu John, and Adrian S. DobsPublished Online:4 May 2007https://doi.org/10.1089/acm.2006.5340AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail FiguresReferencesRelatedDetailsCited byA cross-sectional survey exploring clinician perceptions of a novel Medicaid back pain policy31 October 2022 | Journal of Complementary and Integrative Medicine, Vol. 0, No. 0Perceptions and use of complementary and integrative health practices among rehabilitation professionals: A surveyEuropean Journal of Integrative Medicine, Vol. 55Whole Systems Within Whole Systems: The Oregon Health Plan's Expansion of Services for Back and Neck Pain Emery R. Eaves, Clarissa W. Hsu, Lynn L. DeBar, Catherine J. Livingston, Laura E. Ocker, Sarah J. McDonald, Laurel Dillon-Sumner, and Cheryl Ritenbaugh19 March 2019 | The Journal of Alternative and Complementary Medicine, Vol. 25, No. S1Conocimientos y actitudes sobre la acupuntura en médicos de hospitales y servicios públicos del EcuadorRevista Internacional de Acupuntura, Vol. 11, No. 3Personal and professional influences on practitioners' attitudes to traditional and complementary approaches to health in the UKJournal of Traditional Chinese Medical Sciences, Vol. 1, No. 2"It keeps me going" – older people's perception of well‐being and use of complementary and alternative medicine (CAM)Quality in Ageing and Older Adults, Vol. 13, No. 2Integratieve geneeskunde, een nieuwe zorgvisie24 May 2012 | Tijdschrift voor Kindergeneeskunde, Vol. 79, No. 6Demand for CAM Practice at Hospitals in Japan: A Population Survey in Mie PrefectureEvidence-Based Complementary and Alternative Medicine, Vol. 2011Comparison of knowledge, attitude, and experience about complementary and alternative medicine between primary care physicians and academic physicians in KoreaJournal of the Korean Medical Association, Vol. 54, No. 2Parents' and practitioners' differing perspectives on traditional and complementary health approaches (TCAs) for childrenEuropean Journal of Integrative Medicine, Vol. 2, No. 1Health Care Transitions: A Review of Integrated, Integrative, and Integration ConceptsJournal of Manipulative and Physiological Therapeutics, Vol. 32, No. 9 Volume 13Issue 3Apr 2007 InformationMary Ann Liebert, Inc.To cite this article:Mi-Yeon Song, Majnu John, and Adrian S. Dobs.Clinicians' Attitudes and Usage of Complementary and Alternative Integrative Medicine: A Survey at The Johns Hopkins Medical Institute.The Journal of Alternative and Complementary Medicine.Apr 2007.305-306.http://doi.org/10.1089/acm.2006.5340Published in Volume: 13 Issue 3: May 4, 2007PDF download

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal

This cross-sectional study of adult (137 male, 128 female), urban, community dwelling users and nonusers of illicit drugs evaluated associations of demographic, medical, and drug factors with body composition. The population was 49% HIV-positive and 94% African-American. In multivariate analysis, there were no body composition differences among males based on drug use. Among females, the highest tertile of drug use had less fat (12.3 vs. 19.9 kg, p = .01) and lower body mass index (21.9 vs. 25.1, p = .01) versus less frequent or nonusers. These data suggest a sex difference in body composition associated with drug use.

Objective: To determine if simvastatin effectively decreases the elevated levels of triglyceride (TG), TG-rich lipoproteins, and small, dense LDL particles, which are characteristic of diabetic dyslipidemia.Research design and methods: We conducted a prespecified analysis from a double-blind, placebo-controlled, randomized, 6-week crossover trial in patients with type 2 diabetes and low HDL-C (less than 40 mg/dL). Each patient was randomized to 1 of 6 possible treatment arms; each patient received simvastatin 80 mg, simvastatin 40 mg, and placebo over 3 periods. We used the validated vertical auto profile (VAP dagger) method to directly assess TG-rich lipoproteins and LDL subclasses. We assessed the efficacy of simvastatin to improve the lipoprotein profile in adult men (71%) and women (29%) (n = 151) with stable type 2 diabetes (HbA(1c) < 9%), LDL-C > 100 mg/dL, HDL-C < 40 mg/dL, and fasting TG level > 150 and < 700 mg/dL (median = 273 mg/dL).Main outcome measures: Percentage change from baseline in LDL and VLDL (TG-rich lipoproteins), LDL subclasses, and additional lipoproteins at the end of each 6-week treatment interval; percentage of patients who reached NCEP ATP III non-HDL goal of < 130 mg/dL by the end of each 6-week period.Results: Both simvastatin 80 mg and 40 mg significantly reduced VLDL-C, VLDL3, and IDL, as well as the four LDL subclasses measured with VAP, compared with placebo. Simvastatin 80 mg, compared with simvastatin 40mg, provided additional efficacy. With simvastatin 80 mg, 77.2% of patients not at their non-HDL-C goal of < 130mg/dL at study baseline reached goal, compared with 65.7% following simvastatin 40mg treatment, and 2.2% following placebo.Conclusions: Treatment with simvastatin effectively reduced the elevated levels of TG-rich lipoproteins and improved LDL composition in patients with type 2 diabetes. A large percentage of these patients attained the NCEP ATP III non-HDL-C goal of < 130 mg/dL, which demonstrates the improvement of the atherogenic profile in these patients.

There are an estimated 200 million users of an illicit drug in the world today. In addition, an estimated 40 million people are infected with the human immunodeficiency virus (HIV) and an estimated 180 million people are infected with the hepatitis C virus (HCV). Both the use of an illicit drug and the co-occurrence of infections are associated with a multitude of medical and health consequences including hormonal and metabolic disorders. Thus, the National Institute on Drug Abuse (NIDA), a part of the National Institutes of Health (NIH) hosted a workshop on hormonal and metabolic disorders of HIV among substance abusers. A number of clinicians and scientists participated and discussed a wide range of issues concerning hormones, nutrition and metabolic complications in HIV and substance abuse. Their observations and the recommendations they made for future research are presented in these proceedings. The readers are encouraged to contact the NIH staff (JK, FV) for technical guidance and programmatic priorities on the subject and directly contact the individual authors for collaborations.

Purpose Prostate cancer (PCa) is one of the most common cancers in men. Men with recurrent or metastatic PCa are treated with androgen-deprivation therapy (ADT), resulting in profound hypogonadism. Because male hypogonadism is a risk factor for metabolic syndrome and men with PCa have high cardiovascular mortality, we evaluated the prevalence of metabolic syndrome in men undergoing long-term ADT. Patients and Methods This was a cross-sectional study. We evaluated 58 men, including 20 with PCa undergoing ADT for at least 12 months (ADT group), 18 age-matched men with nonmetastatic PCa who had received local treatment and were recently found to have an increasing prostate-specific antigen (non-ADT group), and 20 age-matched controls (control group). Men in the non-ADT and control groups were eugonadal. Metabolic syndrome was defined according to the Adult Treatment Panel III criteria. Results Mean age was similar among the groups. Men on ADT had significantly higher body mass index and lower total and free testosterone levels. The prevalence of metabolic syndrome was higher in the ADT group compared with the non-ADT (P < .01) and control (P = .03) groups. Among the components of metabolic syndrome, men on ADT had a higher prevalence of abdominal obesity and hyperglycemia. Androgen-deprived men also had elevated triglycerides compared with controls (P = .02). The prevalence of hypertension and low high-density lipoprotein levels were similar. Conclusion These data suggest that metabolic syndrome was present in more than 50% of the men undergoing long-term ADT, predisposing them to higher cardiovascular risk. Abdominal obesity and hyperglycemia were responsible for this higher prevalence. We recommend prospective studies to further delineate this association.

Effectiveness research (a term we use in preference to the more confining and difficult health services or outcomes research) evaluates the clinical setting and the health care system on which it depends. It uses a variety of health care assessment techniques and the practical clinical trial to inform clinical practice, quality interventions, and health policy decisions.Effectiveness research had not had sufficient public or private funding to produce the information needed to facilitate evidence-based health care improvement. However, recent trends, such as the likelihood for continued substantial increases in health care costs and concern regarding the quality and safety of the US health care system, are among the important arguments for increasing its funding and capacity. We propose a new entity, a public-private consortium to expand and offer new capability and resources in this area. The consortium would consist of all relevant public and private entities. It would be organized into an executive committee, which would identify research priorities and panels to design requests for proposals. Competitive peer-reviewed proposals, transparency and balance of forces in choice of topics, conduct of research, and interpretation of results would be important features. Metrics for success would be use of the data derived from consortium projects in medical decision making and benefit design.The consortium would provide balance and potential mediation of conflicting or competing interests in which all stakeholders will be present to establish the rules. Broad representation of all interests would serve to avoid the economic, policy, and political issues that have bedeviled past efforts. Models for the consortium include the Health Effectiveness Institute, the Centers for Education and Research on Therapeutics, and the Transportation Research Board.

The penetration enhancer SEPA (2-n-nonyl-1,3-dioxolane) was formulated in a 1% testosterone hydroalcoholic gel (Opterone (R)) to provide more efficient drug delivery. In a randomized 3-way crossover study in 15 hypogonadal men, testosterone pharmacokinetics (PK) of three daily 1.25 or 2.5 g doses of the SEPA-enhanced gel were compared to three daily 5 g doses of a marketed testosterone gel applied to abdomen skin. Areas under the concentration Vs time curve (AUC) suggested bioequivalence between 2.5 g of Opterone gel and 5 g of the marketed gel. To extend drug delivery to cover 24 hours after application, Opterone was reformulated into a cream. In a second PK study, 32 hypogonadal men were randomly assigned to receive seven daily doses of 3 different amounts of the cream. Maximum serum total testosterone concentrations (C-max) across treatment groups ranged from 400-800 ng/dL, and terminal serum half lives (T-1/2) were approximately 50 hours. This new Opterone cream is currently in human clinical trials.