Oral Enclomiphene Citrate Stimulates the Endogenous Production of Testosterone and Sperm Counts in Men with Low Testosterone: Comparison with Testosterone Gel

IntroductionClomiphene citrate is employed off‐label in men who have low testosterone and for the restoration of sperm counts in men who have used exogenous testosterone. Clomiphene is a mixture of two diastereoisomers: zuclomiphene and enclomiphene. We evaluated enclomiphene citrate in men with secondary hypogonadism.AimOur aim was to compare oral enclomiphene citrate as an alternative to topical testosterone.Main Outcome MeasuresBlood levels of total testosterone (TT), estradiol, follicle‐stimulating hormone (FSH), luteinizing hormone (LH), sex hormone binding globulin, thyroid stimulation hormone, prolactin, and insulin‐like growth factor 1 IGF‐1 were measured at certain times after treatment with each agent. Sperm parameters were determined at the same visits. Free testosterone (FT) was calculated.MethodsThis was a proof‐of‐principle, randomized, open‐label, fixed dose, active‐control, two‐center phase IIB study in 12 men with secondary hypogonadism treated previously with topical testosterone.ResultsAfter discontinuation of topical testosterone, morning TT values averaged 165 ± 66 pg/dL. After 3 months, there was a significant rise in men receiving enclomiphene citrate and gel that was sustained for 3 months. At 6 months, TT levels were 545 ± 268 and 525 ± 256 pg/dL for groups receiving the gel and enclomiphene citrate, respectively. Only men in the enclomiphene citrate group demonstrated increased LH and FSH. TT decreased one month posttreatment to pretreatment values. Enclomiphene citrate elevated sperm counts in seven out of seven men at 3 months and six out of six men at 6 months with sperm concentrations in the 75–334 × 10⁶/mL range. The gel was ineffective in raising sperm counts above 20 × 10⁶/mL for all five men at 3 months and raised counts in only two or five men at 6 months. At follow‐up, only enclomiphene citrate treatment was associated with elevated sperm counts.ConclusionsEnclomiphene citrate increased testosterone and sperm counts. Concomitant changes in LH and FSH suggest normalization of endogenous testosterone production and restoration of sperm counts through the hypothalamic–pituitary–testicular axis.     

Testosterone Replacement with 1% Testosterone Gel and Priapism: No Definite Risk Relationship

IntroductionAlthough testosterone replacement therapy (TRT) is the preferred treatment for hypogonadism, information for patients using testosterone includes too frequent or prolonged erections as a potential side effect.AimTo assess the frequency and risk of priapism or related adverse events (AEs) in hypogonadal men treated with a 1% testosterone gel.MethodsSafety and tolerability data for AndroGel 1% were assessed, including three randomized, controlled clinical trials in varying populations of hypogonadal or near hypogonadal men. Study 1 was a Phase 3 trial of AndroGel 1% 5 g, 7.5 g, or 10 g once daily for 6 months (N = 227). Study 2 was a Phase 2 trial of AndroGel 1% 7.5 g once daily titrated as needed vs. placebo for 26 weeks in men with type 2 diabetes (N = 180). Study 3 was a Phase 4 trial of AndroGel 1% 5 g once daily vs. placebo for 12 weeks in men previously unresponsive to sildenafil 100 mg monotherapy and receiving concomitant sildenafil 100 mg (N = 75). Postmarketing AndroGel pharmacovigilance reporting data from 2001 to 2011 was searched for events coded as priapism.Main Outcome MeasuresThe incidence of priapism and/or related symptoms reported as urogenital or reproductive system AEs.ResultsIn the 283 men exposed to AndroGel 1% over the three trials, mean exposure ranged from 84 days to 149 days. No AEs described as priapism or related symptoms were reported in the three trials. In the postmarketing data, representing 40 million units sold, eight cases described as priapism were reported. Of the six cases with accompanying data, all were judged as possibly related to AndroGel.ConclusionsSafety data from the clinical trials for AndroGel 1% did not report any cases of priapism, and its incidence in the postmarketing pharmacovigilance data is extremely low, indicating a minimal risk of inducing priapism.     

Testosterone and Body Composition in Men after Treatment for Rectal Cancer

IntroductionPreoperative radiotherapy for rectal cancer may affect Leydig cell function. However, the diagnosis of posttreatment hypogonadism is complicated as sexual symptoms associated to hypogonadism can rely on adverse events of pelvic radiation and surgery.AimThe objective of this study was to investigate the association of testosterone levels and body composition. The clinical value of such an association is tested subsequently in the study population.MethodsThis was a longitudinal study with prospective registration during 2010–2012 and 1‐year follow up. Men with rectal cancer stage I–III, treated with radiotherapy and surgery, were eligible, and 40 of 53 men were available for analysis.Main Outcome MeasuresThe areas of skeletal muscle and adipose tissue were assessed on a defined section of a computed tomography at baseline and after 1 year. Androgen levels were recorded from morning blood samples.ResultsThe area of skeletal muscle was related to the level of bioavailable testosterone (P = 0.01) but not to the level of serum testosterone (P = 0.36). The subcutaneous adipose tissue was not related to testosterone levels. Men with posttreatment serum testosterone levels of 8–12 nmol/L and longitudinal loss of psoas muscle area had a significantly increased luteinizing hormone‐testosterone ratio compared with those with longitudinal gain of psoas muscle.ConclusionsThe area of psoas muscle is related to the unbound fraction of circulating testosterone in men treated for rectal cancer. The longitudinal loss of psoas muscle in men with borderline levels of serum testosterone seems to be an androgen‐related symptom associated with compensatory activation of the pituitary–gonadal axis indicating a testicular failure in this group of patients. Buchli C, Tapper J, Bottai M, Holm T, Arver S, Blomqvist L, and Martling A. Testosterone and body composition in men after treatment for rectal cancer. J Sex Med 2015;12:774–782.     

Hypogonadal Men Nonresponders to the PDE5 Inhibitor Tadalafil Benefit from Normalization of Testosterone Levels with a 1% Hydroalcoholic Testosterone Gel in the Treatment of Erectile Dysfunction (TADTEST Study)

IntroductionAddition of testosterone (T) may improve the action of phosphodiesterase type 5 inhibitors (PDE5‐Is) in patients with erectile dysfunction not responding to PDE5‐Is with low or low‐normal T levels.AimsTo confirm this add‐on effect of T in men optimally treated with PDE5‐Is and to specify the baseline T levels at which such an effect becomes significant.MethodsA multicenter, multinational, double‐blind, placebo‐controlled study of 173 men, 45–80 years, nonresponders to treatment with different PDE5‐Is, with baseline total T levels ≤4 ng/mL or bioavailable T ≤ 1 ng/mL. Men were first treated with tadalafil 10 mg once a day (OAD) for 4 weeks; if not successful, they were randomized in a double‐blind, placebo‐controlled design to receive placebo or a 1% hydroalcoholic T gel (50 mg/5 g gel), to be increased to 10 mg T if results were clinically unsatisfactory.Main Outcomes MeasuresMean change from baseline in the Erectile Function Domain Score of the International Index of Erectile Function and rate of successful intercourses (Sexual Encounter Profile 3 question).ResultsErectile function progressively improved over a period of at least 12 weeks in both the placebo and T treatment groups. In the overall population with a mean baseline T level of 3.37 ± 1.48 ng/mL, no additional effect of T administration to men optimally treated with PDE5‐Is was encountered. The differences between the T and placebo groups were significant for both criteria only in the men with baseline T ≤3 ng/mL.ConclusionsThe maximal beneficial effects of OAD dosing with 10 mg tadalafil may occur only after as many as 12 weeks. Furthermore, addition of T to this PDE5‐I regimen is beneficial, but only in hypogonadal men with baseline T levels ≤3 ng/mL. Buvat J, Montorsi F, Maggi M, Porst H, Kaipia A, Colson MH, Cuzin B, Moncada I, Martin‐Morales A, Yassin A, Meuleman E, Eardley I, Dean JD, and Shabsigh R. Hypogonadal men nonresponders to the PDE5 inhibitor tadalafil benefit from normalization of testosterone levels with a 1% hydroalcoholic testosterone gel in the treatment of erectile dysfunction (TADTEST study).     

Absorption of Testosterone Gel 1% (Testim) from Three Different Application Sites

IntroductionA popular treatment choice for male hypogonadism is topical testosterone gel. Two proprietary formulations, Testim Gel 1% (Auxilium Pharmaceuticals, Malvern, PA, USA) and AndroGel 1% (Solvay Pharmaceuticals, Marietta, GA, USA), are available. The recommended Testim application site is limited to the arms/shoulders, whereas AndroGel may be applied to the abdomen, shoulders, and upper arms.AimTo compare absorption variability when applying Testim to various body sites.Main Outcome MeasuresTotal testosterone (TT) and calculated free testosterone (CT_free).MethodsHypogonadal men (TT < 300 ng/mL) applied Testim to three distinct anatomical sites for 1 month per site: arms/shoulders (A), chest/abdomen (C), and calves/legs (L). Pretreatment TT and CT_free were compared with end-of-month measurements. Safety was assessed with prostate-specific antigen (PSA) and hemoglobin (Hb) measurements.ResultsTwenty-one hypogonadal men (age 56.9 ± 9.0) naïve to prior testosterone therapy and otherwise in good health participated. Three groups of seven applied Testim in the sequence ACL, CLA, and LAC. Overall TT and CT_free increased significantly over pretreatment levels (P < 0.0001) into the normal range. Application sites differed with regard to TT levels achieved, A > C ≥ L (P = 0.011). No significant sequence effects were observed, however, the ACL group achieved the highest levels. CT_free correlated well with TT in all men (R² = 0.87) and by application site (R² = 0.91, 0.85, and 0.86 for A, C, L, respectively). Pre- and post-treatment PSAs were similar; mean pretreatment Hb increased from 14.7 ± 1.47 to 15.5 ± 1.3 g/dL at month 3. Hemoglobin corrected to normal in four subjects with anemia at enrollment (Hb < 13.5 g/dL).ConclusionsTestim Gel 1% applied to various anatomical sites increases TT and CT_free into the normal range; the best levels are achieved with arms/shoulder application. Flexibility in the application site of Testim is possible if TT or CT_free is monitored to ensure adequate therapeutic levels. Anemia, possibly associated with testosterone deficiency, was an incidental finding in several men and was corrected with topical testosterone replacement. Guay AT, Smith TM, and Offutt LA. Absorption of testosterone gel 1% (Testim) from three different application sites. J Sex Med 2009;6:2601–2610.     

Increased Body Mass Index Associated with Increased Risky Sexual Behaviors

Study ObjectiveThe increasing prevalence of adolescent obesity has led to consideration of the potential effect of obesity on risky sexual behaviors. In the current study we examined whether body mass index (BMI) was related to age at sexual debut, type of sexual behavior, partner number, and condom use in a population of adolescent women at high risk for obesity and risky sexual behaviors.Design, Setting, and ParticipantsCross-sectional examination of 860 sexually active, predominantly minority, adolescent women who received medical care at an urban health center from 2007 through 2013.Intervention and Main Outcome MeasuresSelf-reported age at sexual debut, types of sexual intercourse, number of partners and condom use was compared with clinically assessed BMI.ResultsBMI was positively associated with number of sexual partners (P = .001) and history of attempted anal intercourse (P = .002). An inverse association was observed with age at first anal intercourse (P = .040).ConclusionIn this sample of adolescent women, increased BMI was associated with riskier sexual practices at a younger age. Results of this study suggest that overweight and obese adolescents are a vulnerable population who might need targeted sexual health counseling.     

Perinatal Outcomes and Satisfaction with Care in Women with High Body Mass Index

Introduction: The majority of studies on pregnant women with high body mass index (BMI) have focused on medical complications and birth outcome, rather than these women's encounters with health care providers. The aims were to identify the proportion of pregnant women with high BMIs (≥30); compare maternal characteristics and pregnancy and birth outcomes; and assess the experiences of prenatal, intrapartum, and postnatal care in women with high (≥30) and lower (<30) BMIs. Methods: Data were collected through questionnaires and antenatal records from 919 women recruited in mid‐pregnancy at 3 hospitals in the north of Sweden, with a follow‐up questionnaire 2 months after birth. Results: The prevalence of obesity was 15.2%. Women with high BMIs were more often aged 35 years or older and less likely to have a university education. They had more negative attitudes regarding being pregnant and reported more childbirth fear compared to women with lower BMIs, but they did not differ in regard to their feelings about the approaching birth or the first weeks with the newborn. They reported more pregnancy complications and had less continuity of caregiver. High BMI was associated with labor induction and emergency cesarean birth. No differences were found in birth complications; birth experience; or satisfaction with prenatal, intrapartum, or postnatal care. Discussion: The findings reveal that women who are obese have more complicated pregnancies and births but are generally satisfied with the care they receive. There are some differences in the way they experience care. Health care providers have a delicate task to provide sufficient information about health risks while still offering respect, encouragement, and support.     

Metabolic Syndrome in Men with Low Testosterone Levels: Relationship with Cardiovascular Risk Factors and Comorbidities and with Erectile Dysfunction

IntroductionTestosterone deficiency and metabolic syndrome (MetS) are strongly associated. Patients consulting for sexual dysfunction may have testosterone deficiency, providing a valuable opportunity to assess MetS. The identification of variables predicting MetS is of great importance.AimsTo identify cardiovascular comorbidities and risk factors, including erectile dysfunction (ED), associated with MetS in men aged ≥45 with total testosterone (TT) < 8 nmol/L (or <12 nmol/L when calculated free testosterone was <250 pmol/L) and to gain further insight into the relationship between both conditions.MethodsData were collected from a multicenter, cross‐sectional, observational study conducted in Spain among men visiting men's health‐care offices with a confirmed diagnosis of testosterone deficiency. Subjects with data for MetS assessment were included in this analysis. Other data available were anthropometrics, toxic habits, cardiovascular comorbidities, ED diagnosis, and TT values.Main Outcome MeasuresThe MetS harmonized definition was used. Waist circumference threshold was 94 cm. ED was diagnosed and classified using the International Index of Erectile Function‐5 (IIEF‐5) questionnaire. Bivariate and multivariate logistic regression analyses were performed to calculate odds ratios (ORs) for MetS.ResultsMean age was 61.2 ± 8.1 years. Prevalences of ED and MetS were 97.6% and 69%, respectively, both increasing with age. Bivariate analysis showed that moderate or severe ED, obesity, and peripheral vascular disease (PVD) were the variables associated with the greatest odds of MetS (OR = 2.672 and 2.514, respectively), followed by alcohol intake (OR = 1.911). Tobacco use, ag,e and testosterone deficiency severity had a minimal effect that disappeared on multivariate analysis. Elevated triglycerides and HDL‐cholesterol were MetS risk factors associated with a lower TT level.ConclusionThe high prevalence of MetS among men with testosterone deficiency highlights the opportunity to assess cardiovascular health in patients consulting for sexual dysfunction. Moderate to severe ED, obesity, PVD, and alcohol intake significantly increase the likelihood of MetS. García‐Cruz E, Leibar‐Tamayo A, Romero J, Piqueras M, Luque P, Cardeñosa O, and Alcaraz A. Metabolic syndrome in men with low testosterone levels: Relationship with cardiovascular risk factors and comorbidities and with erectile dysfunction. J Sex Med 2013;10:2529–2538.     

Are We Testing Appropriately for Low Testosterone?: Characterization of Tested Men and Compliance with Current Guidelines

IntroductionDirect‐to‐consumer ads for testosterone replacement therapies have significantly increased over the past several years. Subsequently, testing for low serum testosterone has correspondingly increased.AimsWe sought to determine the testing behaviors of practitioners as well as the characteristics of men who are undergoing testing for low testosterone.MethodsMen aged 18–85 years were queried from the institutional electronic data warehouse from 2009 to 2012. Men were considered “tested” if their serum total testosterone level had been measured for any purpose. Tested men (TM) were compared with those not tested (NT).Main Outcome MeasuresThe frequency and timing of testing for low testosterone as well as patient demographics and clinical characteristics were compared between TM and NT using multivariable logistic regression models.ResultsOf the 321,674 total men, 10,133 (3.2%) underwent testing with a serum total testosterone (mean age of 55.2 ± 14.1 years). The frequency of testing increased from 2.5% to 3.6% during the study period (P < 0.001). Multivariable analysis demonstrated that TM were significantly (P < 0.001) more likely to be Caucasian and have increased body mass index. In addition, TM were significantly more likely to have comorbid conditions including decreased libido (adjusted odds ratio [aOR] 10.0, 95% confidence interval [CI] 8.5, 11.7), infertility (aOR 4.8, 95% CI 3.6, 6.6), erectile dysfunction (aOR 3.6, 95% CI 3.4, 3.8), osteoporosis (aOR 3.3, 95% CI 2.8, 3.8), depression (aOR 1.7, 95% CI 1.6, 1.8), prostate cancer (aOR 1.7, 95% CI 1.5, 1.8), hypertension (aOR 1.3. 95% CI 1.2, 1.4), chronic obstructive pulmonary disease (aOR 1.2, 95% CI 1.0, 1.4), and benign prostatic hyperplasia (aOR 1.2, 95% CI 1.1, 1.2). Among TM, only 889 (9%) men underwent testing between 7 am and 12 pm.ConclusionsThe rate of testosterone testing is increasing with most testing practices directed toward a subset of men with comorbidities that are associated with hypogonadism. Compliance of physicians obtaining early morning serum testosterone levels is low. Further education of practitioners is required to appropriately test patients for hypogonadism. Malik RD, Lapin B, Wang CE, Lakeman JC, and Helfand BT. Are we testing appropriately for low testosterone?: Characterization of tested men and compliance with current guidelines. J Sex Med 2015;12:66–75.     

Relation Between Dysmenorrhea and Body Mass Index in Adolescents with Rural Versus Urban Variation

Objectives

To find out the relation between the frequency of dysmenorrhea and body mass index in adolescents and to assess the impact of socio-demographic factors, especially rural/urban variation in the frequency of dysmenorrhea.

Methods

Cross-sectional study of 200 urban and 200 rural school going adolescent girls at Udaipur and Bedla Districts, Rajasthan.

Results

Of the 400 girls, the prevalence of dysmenorrhea was found to be very high (81.5 % rural and 76 % urban). In the rural setup, of the total girls with mild dysmenorrhea, 71.84 % had BMI < 16.5, with 27.18 % underweight. All girls with moderate and severe dysmenorrhea had BMI < 16.5. In the urban setup, of all girls with mild dysmenorrhea, 38.05 % had BMI < 16.5 and 54.86 % were underweight. All girls with severe and 80 % with moderate dysmenorrhea had BMI < 16.5. All girls with no dysmenorrhea had normal BMI. There was significant rural versus urban variation.

Conclusions

Relation between dysmenorrhea and BMI was found to be significant (p < 0.01) with increased prevalence in the low BMI group. Hence, improving the nutritional status of adolescent girls may reduce dysmenorrhea.     

Impact of Body Mass Index on In Vitro Fertilization Outcomes

PURPOSE: To determine if body mass index (BMI) impacts IVF outcome. METHODS: Retrospective, cohort study. Main outcome measure was number of oocytes obtained. RESULTS: BMI did not correlate with the prestimulation parameters. There was a significant positive correlation between BMI and the number of follicles on ultrasound prior to egg retrieval. A threshold analysis revealed a significant change in parameters at a BMI > 24 kg/m2. Patients with BMI > 24 kg/m2 demonstrated a significant increase in the number of follicles after stimulation (p = 0.03) and a comparative decrease in the number ampules of gonadotropins used (p = 0.04) and days of stimulation required (p = 0.01). CONCLUSION: These data demonstrated that an elevated BMI significantly correlates with the number of follicles, days of stimulation, and number of ampules of gonadotropins used. Further correlation to an actual increase in number of oocytes and pregnancy rates may be limited by insufficient power in this study.     

Testosterone Replacement Therapy Improves Metabolic Parameters in Hypogonadal Men with Type 2 Diabetes but Not in Men with Coexisting Depression: The BLAST Study

IntroductionThe association between testosterone deficiency and insulin resistance in men with type 2 diabetes is well established and current endocrine society guidelines recommend the measurement of testosterone levels in all men with type 2 diabetes or erectile dysfunction.AimWe report the first double‐blind, placebo‐controlled study conducted exclusively in a male type 2 diabetes population to assess metabolic changes with long‐acting testosterone undecanoate (TU).MethodsThe type 2 diabetes registers of seven general practices identified 211 patients for a 30‐week double‐blind, placebo‐controlled study of long‐acting TU 1,000 mg followed by 52 weeks of open‐label use. Because of the established impact of age, obesity, and depression on sexual function, these variables were also assessed for influence on metabolic parameters.Main Outcome MeasureChanges in glycated hemoglobin (HbA1c) and the level of testosterone at which response are achieved.ResultsTreatment with TU produced a statistically significant reduction in HbA1c at 6 and 18 weeks and after a further 52 weeks of open‐label medication most marked in poorly controlled patients with baseline HbA1c greater than 7.5 where the reduction was 0.41% within 6 weeks, and a further 0.46% after 52 weeks of open‐label use. There was significant reduction in waist circumference, weight, and body mass index in men without depression, and improvements were related to achieving adequate serum levels of testosterone. There were no significant safety issues.ConclusionsTestosterone replacement therapy significantly improved HbA1c, total cholesterol, and waist circumference in men with type 2 diabetes. Improvements were less marked in men with depression at baseline, and therapeutic responses were related to achieving adequate serum testosterone levels. Current advice on 3‐ to 6‐month trials of therapy may be insufficient to achieve maximal response. Patients reported significant improvements in general health. Hackett G, Cole N, Bhartia M, Kennedy D, Raju J, Wilkinson P, and the BLAST Study Group. Testosterone replacement therapy improves metabolic parameters in hypogonadal men with type 2 diabetes but not in men with coexisting depression: The BLAST study. J Sex Med 2014;11:840–856.     

Testosterone Concentrations and Cardiovascular Autonomic Neuropathy in Men with Type 1 Diabetes in the Epidemiology of Diabetes Interventions and Complications Study (EDIC)

IntroductionPrevious studies have reported that lower testosterone concentrations are associated with cardiovascular autonomic neuropathy (CAN), a risk factor for cardiovascular events. However, no studies have examined this relationship in men with type 1 diabetes, who are at high risk for CAN.AimThe aim of this study was to examine the associations between testosterone concentrations and measures of CAN in a large, well-characterized cohort of men with type 1 diabetes.MethodsWe conducted an analysis of men in the Diabetes Control and Complications Trial (DCCT), a randomized trial of intensive glucose control, and its observational follow-up the Epidemiology of Diabetes Intervention and Complications (EDIC) Study. Testosterone was measured by liquid chromatography mass spectrometry in stored samples from EDIC follow-up years 10 and 17. Regression models were used to assess the cross-sectional relationships between testosterone and CAN measures.Main Outcome MeasuresThe main CAN measure from EDIC follow-up year 17 was a standardized composite of R–R variation with paced breathing < 15, or R–R variation 15–20 combined with either a Valsalva ratio ≤ 1.5 or a decrease in diastolic blood pressure > 10 mm Hg upon standing. Continuous R–R variation and Valsalva ratio were secondary outcomes.ResultsLower total and bioavailable testosterone concentrations at follow-up years 10 and 17 were not associated with the presence of CAN at year 17. In analyses using Valsalva ratio as a continuous measure, higher total (P = 0.01) and bioavailable testosterone concentrations (P = 0.005) were associated with a higher (more favorable) Valsalva ratio after adjustment for covariates including age, body mass index, smoking status, hypertension, and glycemia.ConclusionsTestosterone levels are not associated with CAN among men with type 1 diabetes. Although testosterone is associated with a higher Valsalva ratio, a more favorable indicator, the clinical significance of this association is not known.     

Effect of Maternal Body Mass Index on the Retinal Microvasculature in Pregnancy

OBJECTIVE:: To estimate the effects of maternal body mass index (BMI) and pregnancy weight gain on the retinal microvasculature among pregnant women. METHODS:: We studied 814 pregnant women aged 18-46 years who were recruited as part of the Growing Up in Singapore Toward Health Outcomes study, an ongoing birth cohort study from two government hospitals in Singapore since 2009. Recalled prepregnancy weight was recorded, and maternal anthropometric measurements of weight and height were performed at 26 weeks of gestation together with retinal photography. RESULTS:: In multiple linear regression models, each standard deviation increase of 26-week pregnancy BMI (4.57) was associated with narrower retinal arteriolar caliber (by 1.58 micrometers, P<.001), wider venular caliber (by 1.28 micrometers, P=.02), and increased retinal venular tortuosity (P=.01). Compared with mothers with normal weight, obese mothers (prepregnancy BMI greater than 30.0) had narrower retinal arteriolar caliber (118.81 compared with 123.38 micrometers, P<.001), wider retinal venular caliber (175.81 compared with 173.01 micrometers; P<.01), and increased retinal venular tortuosity (129.92 compared with 121.49×10; P<.01). Pregnant women whose BMI-specific weight gain from prepregnancy to 26 weeks of gestation was above Institute of Medicine recommendations had narrower retinal arteriolar caliber (120.68 micrometers) than women with ideal (121.91 micrometers) and less than ideal weight gain (123.17), respectively (Ptrend=.05). CONCLUSION:: These data indicate that greater prepregnancy BMI and pregnancy BMI are associated with adverse retinal microvascular measures, suggesting that maternal obesity has an effect on her microcirculation. LEVEL OF EVIDENCE:: III.     

Coadministration of Anastrozole Sustains Therapeutic Testosterone Levels in Hypogonadal Men Undergoing Testosterone Pellet Insertion

IntroductionCurrent U.S. Food and Drug Administration–approved therapies for hypogonadism involve testosterone (T) replacement. Testosterone pellets (TP) require a minor office procedure every 3 to 4 months. The need for repeated insertions increases the likelihood of a complication. Anastrozole (AZ) is an aromatase inhibitor that has been used off-label for the treatment of male hypogonadism. AZ increases T levels by lowering serum estradiol (E2) levels and increasing gonadotropin (GTP) levels.AimWe hypothesized that the concomitant use of AZ with TP insertions would sustain therapeutic T levels and increase the interval between TP insertions.MethodsMen treated with TP for hypogonadism at an academic center were offered AZ (1 mg/day) at the time of TP reinsertion as a way of potentially decreasing the frequency of TP insertions. Total T (TT), free T (FT), sex hormone binding globulin, E2, luteinizing hormone (LH), and follicle-stimulating hormone FSH levels were obtained prior to T replacement and at 6 and 15 weeks from TP insertion. Men were re-implanted at 16 weeks if their TT levels were less than 350 ng/dL and their symptoms recurred. We retrospectively reviewed our records of men who underwent TP, TP, and AZ from 2011 to 2012. Demographics, TT, FT, LH, FSH, and E2 levels were recorded. Data were analyzed with anova and a Tukey's test.Main Outcome MeasureTT level at 6, 15, or >15 weeks from TP insertion.ResultsThirty-eight men with 65 insertions were analyzed. The TP AZ group had significantly higher TT and FT levels than the TP group at >120 days (P < 0.05). The TP group had significantly higher E2 levels at all time points (P < 0.01). GTP levels remained stable in the TP AZ group. Average time to reinsertion in TP AZ was 198 days vs. 128 days in the TP group.ConclusionMen on TP AZ maintain therapeutic T levels longer than men on TP alone and have significantly less GTP suppression. Mechlin CW, Frankel J, and McCullough A. Coadministration of anastrozole sustains therapeutic testosterone levels in hypogonadal men undergoing testosterone pellet insertion. J Sex Med 2014;11:254–261.