Effects of Aerobic Exercise Combined with Oyster Peptide Supplement on the Formation of CTX-induced Late-Onset Hypogonadism in Male Rats.

The purpose of this study is to investigate the effect of aerobic exercise (AE) training and/or oyster peptide (OP) supplementation on the formation of late-onset hypogonadism (LOH). AE training and/or OP supplement was performed during Cytoxan (CTX)-induced LOH formation in male SD rats for 6 consecutive weeks. Low dose of CTX could decrease mating times, the levels of luteinizing hormone (LH), total testosterone (TT), free testosterone (FT) in serum and TT, androgen receptor (AR), androgen binding protein (ABP), and glutathione peroxidase (GSH-Px) in testicle, but increase capture latency, mating latency, and malondialdehyde, and downregulate the mRNA expression of steroidogenic acute regulatory (StAR), P450 cholesterol side chain cleavage enzyme (P450scc), and StAR-related lipid transfer domain 7 (StARD7) in testicle. Every change was altered by AE training combined with OP supplement significantly, except for serum LH. Moreover, the effect of AE training combined with OP supplement was better than that of AE training on serum TT, FSH, testicular TT, mating latency, capture times, and mating times. AE training combined with OP supplement during CTX-induced LOH formation can prevent the LOH development by enhancing pituitary-gonads axis's function and reducing testicular oxidative stress to promote testosterone synthesis and spermatogenesis.

BaZiBuShen alleviates altered testicular morphology and spermatogenesis and modulates Sirt6/P53 and Sirt6/NF-κB pathways in aging mice induced by D-galactose and NaNO2.

ETHNOPHARMACOLOGICAL RELEVANCE: Sperm infertility and testicular atrophy are symptoms associated with aging. BaZiBuShen formula (BZBS), a patented Chinese herbal prescription composed of Semen Cuscutae, Fructus Lycii, Epimedii Folium, Fructus Schisandrae Sphenantherae, Fructus Cnidii, Fructus Rosae Laevigatae, Semen Allii Tuberosi., Radix Morindae Officinalis, Herba Cistanches, Fructus Rubi, Radix Rehmanniae Recens, Radix Cyathulae, Radix Ginseng, Cervi Cornu Pantotrichum, Hippocampus, and Fuctus Toosendan, has been used as a kidney-tonifying and anti-aging drug as well as for the treatment of impotence and male infertility in traditional Chinese medicine. AIM OF THE STUDY: We aimed at investigating whether BZBS preserves sperm and testes morphology in aging mice, and to explore the underlying mechanisms. MATERIALS AND METHODS: BZBS was orally administered to aging mice induced by D-galactose (D-gal) and NaNO2 for 65 days. Sperm quality and testes pathophysiological alterations were examined by a Semen Analysis System, hematoxylin-eosin staining, transmission electron microscopy, and mitochondrial complex IV activity. In addition, serum levels of total antioxidant capacity (TAC), malondialdehyde (MDA), 8-hydroxy-desoxyguanosine (8-OH-dG), reduced glutathione (GSH), oxidized glutathione disulfide (GSSG), testosterone (T), follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) and tumor necrosis factor-α (TNF-α) were determined by ELISA. The expressions of P450 aromatase (CYP19), sirtuin 6 (Sirt6), P53, inducible nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-κB)-p65, and phospho-NF-κB-p65 (NF-κB-pp65) in the testes were examined by western blot and/or immunohistochemical staining. RESULTS: Sustained exposure to D-gal/NaNO2 caused a deterioration of sperm quality and testes morphology in this rapid aging mouse model. BZBS treatment curtailed these alterations. These beneficial effects were associated with increased serum levels of TAC, GSH/GSSG, T, E2, and FSH, and decreased levels of MDA, TNF-α, and 8-OH-dG. BZBS treatment also downregulated the expressions of P53, iNOS, and NF-κB-pp65, as well as upregulated the expressions of Sirt6 and CYP19 in aging testes. CONCLUSIONS: BZBS preserves testicular morphology and spermatogenesis possibly via inhibition of oxidative stress and the modulation of the Sirt6/P53 and Sirt6/NF-κB signaling pathways. The results shed light on the beneficial effect of BZBS on sperm quality and fertility in aging males.

Opioid-induced endocrinopathies.

The use of opioids is becoming a global epidemic, leading to a rise in the occurrence and recognition of the effects of opioid drugs on the endocrine system. Nonetheless, opioid-induced endocrinopathies still remain underdiagnosed, mainly because of symptom under-reporting by patients and poor clinician awareness. Hypogonadism is the most well recognised consequence of opioid use, but the inhibitory effects of opioid drugs on the hypothalamo-pituitary-adrenal axis and their negative effects on bone health also require attention. Hyperprolactinaemia might be detected in opioid users, but clinically relevant thyroid dysfunction has not been identified. The effects of opioids on other hormones have not been clearly defined. Assessment of gonadal and adrenal function (particularly if high index of clinical suspicion of hypogonadism or hypoadrenalism) and evaluation of bone health are advised in people that use opiods. Discontinuation or reduction of opioid dose and appropriate hormone replacement are the management approaches that should be considered for hypogonadism and hypoadrenalism. Further research is needed to facilitate the development of evidence-based guidelines on the diagnosis and optimal management of opioid-induced endocrinopathies.

Male and female sexual dysfunction in diabetic subjects: Focus on new antihyperglycemic drugs.

The association between diabetes mellitus (and its micro- and macro-vascular complications) and erectile dysfunction is widely known and the presence of hypogonadism may further complicate sexual dysfunction and quality of life, given the association between hypogonadism and reduced libido, ejaculatory disorders, and depressive symptoms. However, the recent introduction of novel antidiabetic agents with a wide range of mechanism of action may have a significant impact both on male and female sexuality directly (by inducing side effects as urinary tract infections) and indirectly (improving metabolic status and reducing diabetes complications behind sexual dysfunctions). To date only few papers are reporting the sexual effects of these treatments and, often, these are not comparable in their results. Conversely, female sexual dysfunctions are somehow under-investigated. Data on prevalence is heterogeneous and specific pathogenic mechanisms, as well as the burden of psychological factors, are still heatedly debated. The aim of this narrative review is to summarize current knowledge and stressing out the need to diagnose male and female sexual dysfunctions also in light of the impact of treatments with novel antidiabetic agents. This would highlight the still unmet needs for sexual care in a diabetes care setting and could represent an incentive for future discussions, as well as a required theoretical starting point for studies on this subject.

Opioid-induced hypogonadism: Pathophysiology, clinical and therapeutics review.

Opioids are pivotal therapeutics in the management of escalated chronic pain (moderate-severe). In the last two decades, the increased prescription rate and the prolonged usage of opioids shed light on opioid-induced endocrinopathy. Opioid-induced hypogonadism (OHG) results upon long-term opioid therapy. Clinically, patients with OHG are presented mainly by sexual dysfunction and infertility. Opioid clinical use in pain therapy is indispensable. However, the resultant sexual endocrinopathy cannot be overlooked and hence hormonal replacement therapy with regular monitoring of the patients represents a potential therapeutic strategy while avoiding opioids in patients with guaranteed long therapeutic exposure and switching to using low-dose naltrexone as alternative represents a possible prophylactic measure to ensure therapeutic compliance and secure a good life quality of patients.

The prevalence of low serum free testosterone and the short-term effect of anti-retroviral therapy in male Japanese treatment-naïve HIV patients.

OBJECTIVES: The prevalence of hypogonadism in HIV patients is still a matter of debate. Today, serum free testosterone (fTST) is thought to be more important than serum testosterone in the diagnosis of hypogonadism in patients with HIV. This study aimed to determine the prevalence of low fTST levels and the effects of anti-retroviral therapy (ART) on fTST levels in treatment-naïve male Japanese patients with HIV. METHODS: Patients who visited Teikyo University Hospital, Japan between 2010 and 2016 were enrolled. Patients' fTST levels were evaluated twice with a radioimmunoassay in the morning, at the onset of ART and one year later. Clinical factors were also reviewed. The patients were divided into two groups ('hypogonadism' and 'normal') based on Japanese criteria. To determine factors related to low fTST in treatment-naïve patients, the Mann-Whitney U test and a multiple-regression analysis were used. Changes in fTST levels after ART initiation were evaluated with a paired t-test. RESULTS: Data from 25 patients were collected. Their median age was 36.0 years, and the median fTST level was 8.00 pg/ml in the treatment-naïve state. Thirteen patients (52%) were in the hypogonadism group. Low levels of fibroblast growth factor 23 were significantly related to low fTST levels. After the start of ART, fTST levels increased significantly (median 8.00 interquartile range [6.40-9.70] to 9.60 [7.60-13.10] pg/ml, p = 0.0081). CONCLUSIONS: Subnormal fTST levels occurred frequently among the present study patients in treatment-naïve settings. Free testosterone levels in patients with HIV were significantly increased one year after the start of ART.

[Evaluation of testosteronemia in men undergoing surgery for urethral strictures].

INTRODUCTION: Testosterone plays an important role in the functioning of various organs and systems of the male body. Its diagnostic and prognostic values are studied both in urological diseases and in the patients undergoing non-urologic surgery. AIM: To investigate changes in testosterone level in patients with urethral strictures (US) depending on its baseline level, the cause of US, the age of patients and the number of surgeries. MATERIALS AND METHODS: The study comprised 30 patients aged 19-63 years with traumatic (76.7%) and inflammatory (23.3%) US. Primary and recurrent US were diagnosed in 25 (83.3%) and 5 (16.7%) patients, respectively. Nineteen (63.3%) patients underwent excision and primary anastomosis, while replacement urethroplasty was performed in 11 (36.7%) patients. In addition to the standard diagnostic work-up, all patients were tested for total serum testosterone 24 hours prior to surgery and at 1, 3, 7, 14 days after the operation. RESULTS: 33.3% of men with US had a testosterone deficiency in the absence of any testicular or endocrine injuries and diseases. Surgery was associated with a drop in testosteronemia in 83.3% of patients. The degree of postoperative testosterone level decline and its changes were significantly influenced by the age of patients and the number of operations. Men who had baseline testosterone deficiency and underwent repeat surgeries remained in a hypogonadal state throughout the postoperative period. CONCLUSION: Investigating the clinical value of testosterone in men with US and the risks of their surgical treatment associated with testosterone deficiency will provide insight into the role of testosterone in the treatment of this condition and the decision-making regarding pharmacological correction of testosterone deficiency in patients undergoing surgery for US.

Response to growth hormone treatment in very young patients with growth hormone deficiencies and mini-puberty.

BACKGROUND: The aim of the study was to assess the response to growth hormone (GH) treatment in very young patients with GH deficiency (GHD) through a national, multi-center study. Possible factors affecting growth response were assessed (especially mini-puberty). METHODS: Medical reports of GHD patients in whom treatment was initiated between 0 and 3 years of age were retrospectively evaluated. RESULTS: The cohort numbered 67. The diagnosis age was 12.4±8.6 months, peak GH stimulation test response (at diagnosis) as 1.0±1.4 ng/mL. The first and second years length gain was 15.0±4.3 and 10.4±3.4 cm. Weight gain had the largest effect on first year growth response; whereas weight gain and GH dose were both important factors affecting second year growth response. In the multiple pituitary hormone deficiency (MPHD) group (n=50), first year GH response was significantly greater than in the isolated GH deficiency (IGHD) group (n=17) (p=0.030). In addition first year growth response of infants starting GH between 0 and 12 months of age (n=24) was significantly greater than those who started treatment between 12 and 36 months of age (n=43) (p<0.001). These differences were not seen in the second year. Δ Length/height standard deviation score (SDS), Δ body weight SDS, length/height SDS, weight SDS in MPHD without hypogonadism for the first year of the GH treatment were found as significantly better than MPHD with hypogonadism. CONCLUSIONS: Early onsets of GH treatment, good weight gain in the first year of the treatment and good weight gain-GH dose in the second year of the treatment are the factors that have the greatest effect on length gain in early onset GHD. The presence of the sex steroid hormones during minipubertal period influence growth pattern positively under GH treatment (closer to the normal percentage according to age and gender).

Prevention of CCl4 induced hypogonadism with Raphanus sativus seeds in rat.

Raphanus sativus seeds are used as condiment and to treat hypogonadism, various ailments of liver and kidneys. The aim of this study was to evaluate the potential protective effects of methanol extract of R. sativus seeds (RSME) against hypogonadism induced with carbon tetrachloride (CCl4) in Sprague-Dawley male rats. Thirty six rats were divided in to six groups with six animals in each. Animals of Group I were control and treated with saline, Group II, III and IV were given orally CCl4 (1 ml/kg bw; 10% in corn oil). Rats of Group III and IV were also simultaneously given RSME at 100 mg/kg bw and 200 mg/kg bw respectively. However, Group V and VI received RSME (100; 200 mg/kg bw, respectively) alone. All treatments were given at alternate days for 15 days. Treatment of CCl4 to rats decreased (P < 0.001) the level of CAT, POD, SOD, GST, GSH-Px and GSR antioxidant enzymes in testes of rat. Concentration of lipid peroxides (TBARS) was increased (P < 0.001) whereas concentration of GSH was decreased (P < 0.001) in testes of CCl4 treated animals. Concentration of testosterone, FSH and LH in serum was decreased (P < 0.001) while the level of estradiol and prolactin was increased (P < 0.001) in CCl4 treated rats. Injuries in seminiferous tubules were determined in histopathology of testes. Administration of RSME, dose dependently, markedly ameliorated the oxidative stress of CCl4 thereby restoring the level of antioxidant enzymes, lipid peroxides, reduced glutathione, male hormones and alterations in histopathology.

Long-Term Follow-Up of Primary Medical Versus Surgical Treatment of Prolactinomas in Men: Effects on Hyperprolactinemia, Hypogonadism, and Bone Health.

OBJECTIVE: In men with prolactinomas, impaired bone density is the principle consequence of hyperprolactinemia-induced hypogonadism. Although dopamine agonists (DAs) are the first-line approach in prolactinomas, surgery can be considered in selected cases. In this study, we aimed to investigate the long-term control of hyperprolactinemia, hypogonadism, and bone health comparing primary medical and surgical therapy in men who had not had prior DA treatment. METHODS: This is a retrospective case-note study of 44 consecutive men with prolactinomas and no prior DAs managed in a single tertiary referral center. Clinical, biochemical, and radiologic response to the first-line approach were analyzed in the 2 cohorts. RESULTS: Mean age at diagnosis was 47 years (range, 22-78 years). The prevalence of hypogonadism was 86%, and 27% of patients had pathologic bone density at baseline. The primary therapeutic strategy was surgery for 34% and DAs for 66% of patients. Median long-term follow-up was 63 months (range, 17-238 months). Long-term control of hyperprolactinemia required DAs in 53% of patients with primary surgical therapy, versus 90% of patients with primary medical therapy (P = 0.02). Hypogonadism was controlled in 73% of patients. The prevalence of patients with pathologic bone density was 37% at last follow-up, with no differences between the 2 therapeutic cohorts (P = 0.48). CONCLUSIONS: Despite control of hyperprolactinemia and hypogonadism in most patients independent of the primary treatment modality, the prevalence of impaired bone health status remains high, and osteodensitometry should be recommended.

[Testosterone therapy]. / Testosterontherapie.

Hormone replacement therapy with testosterone has become well-established over the course of time. The initial substantial concerns with respect to complications and potential adverse events, particularly in older patients, were proven to be unfounded over time. Testosterone therapy has therefore gradually become a regular treatment modality in urological practice. It has also been shown to represent a valuable tool as supportive treatment for patients with erectile dysfunction and hypogonadism. A variety of testosterone preparations are available for treatment. Recent pharmaceutical developments have greatly improved the practicability and ease of administration for patients. Several guidelines have been developed that provide clearly formulated standards and instructions for indications, contraindications, application, risk factors and monitoring of testosterone therapy. Adverse events affecting the cardiovascular system and especially diseases of the prostate gland are of great importance, thus making the urologist the primary partner in the treatment of patients with testosterone deficiency.

Longitudinal changes of endocrine and bone disease in adults with ß-thalassemia major receiving different iron chelators over 5 years.

In this study, we compared the long-term effects of different iron chelation regimens (deferoxamine, deferiprone, deferoxamine + deferiprone, and deferasirox) in preventing or reversing endocrinopathy (diabetes mellitus, hypothyroidism, or hypogonadism) and bone disease (measured through DEXA) in 165 adults with ß-thalassemia major (TM) (mean age 39.9 ± 8.3 years, 43 % males). After five consecutive years of therapy, patients on deferasirox had the highest decrease in the prevalence of any endocrinopathy compared to other chelators which either had no change (deferiprone and deferoxamine) or had an increase (deferoxamine + deferiprone), p = 0.015. This was attributed to a lower proportion of patients on deferasirox developing new-onset endocrinopathy and higher proportion showing reversal of disease, compared to other chelators. A serum ferritin level of >1300 ng/mL predicted the development of new endocrinopathy (p = 0.025) while a level of <200 ng/mL predicted reversal of existing endocrinopathy (p = 0.147). A significant increase in mean BMD T-score (p < 0.001) and a considerable decrease in osteoporosis prevalence were observed in patients receiving deferasirox but not other chelators. Iron chelation therapy with deferasirox has a role in the prevention of endocrinopathy and reversal of existing disease.

[Urological Diseases in Men and their Prevention]. / Urologische Erkrankungen des Mannes und deren Prävention.

The late-onset hypogonadism is defined as a reduction of blood testosterone values in aging males in combination with sexual symptoms. A hormone substitution is only necessary if desired by the patient. Erectile dysfunction is often caused by vasculopathy. Therefore, vascular risk factors should be evaluated. In case of cardiovascular disease a cardiologist should be addressed before initiating treatment. First line therapy consists of phosphodiesterase inhibitors. In lower urinary tract symptoms prostatic enlargement is the likely cause, but other causes have to be ruled out. Symptomatic therapy can be initiated if the patient is bothered. If voiding symptoms are predominant, alpha blockers or alpha reductase inhibitors are the treatment of choice. In case of storage symptoms, treatment can be started with muscarin receptor antagonists.

Improved versus worsened endocrine function after transsphenoidal surgery for nonfunctional pituitary adenomas: rate, time course, and radiological analysis.

OBJECTIVE: The impact of transsphenoidal surgery for nonfunctional pituitary adenomas (NFAs) on preoperative hypopituitarism relative to the incidence of new postoperative endocrine deficits remains unclear. The authors investigated rates of hypopituitarism resolution and development after transsphenoidal surgery. METHODS: Over a 5-year period, 305 transsphenoidal surgeries for NFAs performed at The California Center for Pituitary Disorders were retrospectively reviewed. RESULTS: Patients with preoperative endocrine deficits (n = 153, 50%) were significantly older (mean age 60 vs 54 years; p = 0.004), more frequently male (65% vs 44%; p = 0.0005), and had larger adenomas (2.4 cm vs 2.1 cm; p = 0.02) than patients without preoperative deficits (n = 152, 50%). Of patients with preoperative endocrine deficits, 53% exhibited symptoms. Preoperative deficit rates were 26% for the thyroid axis; 20% and 16% for the male and female reproductive axes, respectively; 13% for the adrenocorticotropic hormone (ACTH)/cortisol axis, and 19% for the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis. Laboratory normalization rates 6 weeks and 6 months after surgery without hormone replacement were 26% and 36% for male and 13% and 13% for female reproductive axes, respectively; 30% and 49% for the thyroid axis; 3% and 3% for the cortisol axis; and 9% and 22% for the IGF-1 axis (p < 0.05). New postoperative endocrine deficits occurred in 42 patients (13.7%). Rates of new deficits by axes were: male reproductive 3% (n = 9), female reproductive 1% (n = 4), thyroid axis 3% (n = 10), cortisol axis 6% (n = 19), and GH/IGF-1 axis 4% (n = 12). Patients who failed to exhibit any endocrine normalization had lower preoperative gland volumes than those who did not (0.24 cm(3) vs 0.43 cm(3), respectively; p < 0.05). Multivariate analyses revealed that no variables predicted new postoperative deficits or normalization of the female reproductive, cortisol, and IGF-1 axes. However, increased preoperative gland volume and younger age predicted the chances of a patient with any preoperative deficit experiencing normalization of at least 1 axis. Younger age and less severe preoperative hormonal deficit predicted normalization of the thyroid and male reproductive axes (p < 0.05). CONCLUSIONS: After NFA resection, endocrine normalization rates in this study varied with the hormonal axis and were greater than the incidence of new endocrine deficits. Low preoperative gland volume precluded recovery. Patient age and the severity of the deficiency influenced the recovery of the thyroid and male reproductive axes, the most commonly impaired axes and most likely to normalize postoperatively. This information can be of use in counseling patients with hypopituitarism who undergo NFA surgery.

Erectile function in men with end-stage liver disease improves after living donor liver transplantation.

BACKGROUND: Impaired liver function in men can result in erectile dysfunction or hypogonadism or both. We investigated whether living donor liver transplantation (LDLT) results in improvement in male sexual function. METHODS: A total of 58 patients with end-stage liver disease (ESLD) were included in this prospective, cross-sectional study. Erectile function was measured before and after LDLT using a five-item modified version of the International Index of Erectile Function scale (IIEF-5) and hypogonadism was evaluated before and after LDLT using the Androgen Deficiency in the Aging Male (ADAM) questionnaire. Differences in mean values from the questionnaires before and after the operation were than evaluated to determine whether there is an association between LDLT and improvement in sexual function. RESULTS: We found that mean IIEF-5 scores significantly increased after LDLT (from 11.7 ± 7.7 before LDLT to 14.7 ± 7.5 after LDLT, p < 0.01), indicating that the operation played a role in improving erectile function. In addition, the prevalence of hypogonadism among the patients with ESLD decreased markedly after liver transplantation (hypogonadism before LDLT, n = 41 versus hypogonadism after LDLT, n = 31, p = 0.03). Patients with hypogonadism reported a higher prevalence of erectile dysfunction after LDLT than patients without hypogonadism (p < 0.01). CONCLUSIONS: LDLT results in improvement in erectile function. In addition, improvement in erectile function is associated with self-reported absence of hypogonadism.

Restoring testosterone levels by adding dehydroepiandrosterone to a drospirenone containing combined oral contraceptive: I. Endocrine effects.

OBJECTIVES: Combined oral contraceptives (COCs) decrease testosterone (T) levels. This study investigated restoration of T and other androgen concentrations during COC use by 'co-administration' of dehydroepiandrosterone (DHEA). STUDY DESIGN: In this randomized, double-blind, placebo-controlled study in 99 new COC starters (18-35 years old with body mass index range 18-34 kg/m²), a COC containing 30mcg ethinylestradiol (EE) and 3 mg drospirenone (DRSP) was used for 3cycles, followed by 6cycles of the same COC combined with either 50 mg/day DHEA or placebo. Total T, albumin, sex hormone-binding globulin (SHBG), DHEA-sulfate (DHEA-S), Δ4-androstenedione (AD), 3α-androstanediol glucuronide (ADG) and estradiol (E2) were measured, whereas free T and the free T index (FTI) were calculated. Assessments took place at baseline (no COC use), after the run-in period (COC use alone) and during the treatment period (DHEA or placebo). RESULTS: During COC use alone, androgen levels decreased, especially total T by 62% and free T by 86%, and SHBG increased by 243%. Total T increased with DHEA compared to placebo (change from end of run-in period to end of treatment period -- 1.3±1.2 nmol/L vs. 0.0±0.4 nmol/L; p<.0001) -- and was restored to baseline levels. Free T and the FTI increased significantly (p<.0001), but the free T level was still 53% below baseline levels. DHEA-S, AD and ADG increased significantly to levels above baseline (p<.0001 for each). DHEA had no effect on SHBG, albumin and E2. CONCLUSIONS: An EE/DRSP containing COC strongly suppressed endogenous androgen concentrations in all users. The addition of 50 mg DHEA to a COC regimen containing EE/DRSP restored total T to baseline levels, but free T levels were restored by only 47% as most of the T remains bound to SHBG. IMPLICATIONS: When using a COC that increases SHBG considerably, a daily dose of 50 mg DHEA is insufficient to normalize free T levels completely.

The impact of obesity on male fertility.

Obesity in men of reproductive age is globally on the increase. There is clear evidence from epidemiological studies that obesity impacts negatively on male fertility; it is associated with hypogonadism, although it is less consistently linked to impaired spermatogenesis and tests of sperm function, including DNA fragmentation. Sperm from obese men used for in vitro fertilisation/intra cytoplasmic sperm injection is associated with a greater number of pregnancy losses and is less likely to result in live births. There are also increasing data from animal studies that paternal obesity may impact negatively on the reproductive and metabolic health of offspring and grand-offspring. It has been suggested that high-fat dietary exposures could affect the epigenetic content of sperm or the endocrine content of seminal fluid and thus impact early fetal development. Experimental and epidemiological data show that male fertility, and offspring health, can be improved by weight loss in obese and overweight males.

Restoring testosterone levels by adding dehydroepiandrosterone to a drospirenone containing combined oral contraceptive: II. Clinical effects.

OBJECTIVES: Combined oral contraceptives (COCs) decrease androgen levels, including testosterone (T), which may be associated with sexual dysfunction and mood complaints in some women. We have shown that 'co-administration' of dehydroepiandrosterone (DHEA) to a drospirenone (DRSP)-containing COC restored total T levels to baseline and free T levels by 47%. Here we describe the effects on sexual function, mood and quality of life of such an intervention. STUDY DESIGN: This was a randomized, double-blind, placebo-controlled study in 99 healthy COC starters. A COC containing 30 mcg ethinylestradiol (EE) and 3 mg DRSP was used for three cycles, followed by six cycles of the same COC combined with 50 mg/day DHEA or placebo. Subjects completed the Moos Menstrual Distress Questionnaire (MDQ), the McCoy Female Sexuality Questionnaire and the short form of the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q). Safety and tolerability, including effects on skin, were evaluated. RESULTS: The addition of DHEA induced small but significant improvements compared to placebo in the MDQ score for autonomic reactions during the menstrual (-2.0 vs. 0.71; p=0.05) and the premenstrual phase (-3.1 vs. 2.9; p=0.01) and for behavior during the intermenstrual phase (-1.4 vs. 3.6; p=0.02). A significant difference was found in the MDQ score for arousal during the premenstrual phase in favor of placebo (-5.0 vs. 1.0; p=0.01). There were no statistically significant differences between groups for the MSFQ and Q-LES-Q scores. DHEA 'co-administration' resulted in an acceptable safety profile. DHEA negated the beneficial effect of the COC on acne according to the subjects' self-assessment. CONCLUSIONS: 'Co-administration' with DHEA did not result in consistent improvements in sexual function, mood and quality of life indicators in women taking EE/DRSP. Retrospectively, the 50 mg dose of DHEA may be too low for this COC. IMPLICATIONS: A well-balanced judgment of the clinical consequences of normalizing androgens during COC use may require complete normalization of free T.