Gigantol Improves Cholesterol Metabolism and Progesterone Biosynthesis in MA-10 Leydig Cells

In aging males, androgen production by testicular Leydig cells decreases at a rate of approximately 1% per year. Phenolic compounds may enhance testosterone biosynthesis and delay the onset of male hypogonadism. Gigantol is a bibenzyl compound isolated from several types of orchids of the genus Dendrobium. This compound has various biological activities, including antioxidant activity. However, its capacity to regulate gene expression and steroid production in testicular Leydig cells has never been evaluated. We investigated the effect of gigantol on MA-10 Leydig cells’ gene expression using an RNA-Seq approach. To further investigate the structure-function relationship of the hydroxy-methoxyphenyl moiety of gigantol, experiments were also performed with ferulic acid and isoferulic acid. According to transcriptomic analysis, all genes coding for cholesterol biosynthesis-related enzymes are increased in response to gigantol treatment, resulting in increased lipid droplets accumulation. Moreover, treatments with 10 μM gigantol increased StAR protein levels and progesterone production from MA-10 Leydig cells. However, neither ferulic acid nor isoferulic acid influenced StAR protein synthesis and progesterone production in MA-10 Leydig cells. Thus, our findings indicate that gigantol improves cholesterol and steroid biosynthesis within testicular Leydig cells.

Hypogonadism in male infants and adolescents: new androgen formulations

Background Male hypogonadism may be associated with micropenis and cryptorchidism in newborn, absent or incomplete pubertal development when it occurs during childhood. During puberty, androgen replacement therapy plays a pivotal role in subjects with hypogonadism to induce sexual maturation, growth acceleration, anabolic effects on fat-free mass growth increasing muscle strength, directly and indirectly on the attainment of peak bone mass in young men. Moreover, in newborns with congenital hypogonadism, androgen therapy could be effective to increase genital size. Summary Testosterone replacement therapy (TRT) represents the cornerstone of the management of hypogonadism in boys. During puberty, replacement therapy needs to be modulated with gradual dosing increase to better mimic the physiologic pubertal development. Currently, intramuscular testosterone esters (in particular testosterone enanthate, TE) and subcutaneous testosterone pellets are the only formulations approved by the US Food and Drug Administration (FDA) for delayed puberty, while no preparation is approved for long-term use in the adolescent age. Several new testosterone (T) formulations (as transdermal, nasal, subcutaneous, and oral formulation) are recently developed to improve the pharmacokinetic profile and to ease the administration route increasing patient compliance in adult males with hypogonadism. All these formulations are not approved for pediatric age, although some of them are used as “off-label” regimens. This special issue is aimed to illustrate new T formulations and their potential role as replacement therapy in the pediatric population, as well as to highlight investigational areas to contribute to health care improvement in these patients. Key Messages. Despite the lack of evidence-based guidelines regarding the choice of T formulation in the pediatric population, new formulations appear to have a potential role for TRT in adolescent age. They have been designed for adult age with a little flexibility of dosage, although a few formulations may be attractive for pubertal induction and penile enlargement thanks to their greater flexibility and easing of administration. On the other hand, long-acting and stable formulations could meet post-pubertal needs, increasing TRT compliance in a critical phase as the adolescent age. Further controlled, long-term safety, and efficacy studies for all these new T formulations within the pediatric population are needed.

The Mechanisms and Management of Age-Related Oxidative Stress in Male Hypogonadism Associated with Non-communicable Chronic Disease

Androgens have diverse functions in muscle physiology, lean body mass, the regulation of adipose tissue, bone density, neurocognitive regulation, and spermatogenesis, the male reproductive and sexual function. Male hypogonadism, characterized by reduced testosterone, is commonly seen in ageing males, and has a complex relationship as a risk factor and a comorbidity in age-related noncommunicable chronic diseases (NCDs), such as obesity, metabolic syndrome, type 2 diabetes, and malignancy. Oxidative stress, as a significant contributor to the ageing process, is a common feature between ageing and NCDs, and the related comorbidities, including hypertension, dyslipidemia, hyperglycemia, hyperinsulinemia, and chronic inflammation. Oxidative stress may also be a mediator of hypogonadism in males. Consequently, the management of oxidative stress may represent a novel therapeutic approach in this context. Therefore, this narrative review aims to discuss the mechanisms of age-related oxidative stress in male hypogonadism associated with NCDs and discusses current and potential approaches for the clinical management of these patients, which may include conventional hormone replacement therapy, nutrition and lifestyle changes, adherence to the optimal body mass index, and dietary antioxidant supplementation and/or phytomedicines.

Reproductive endocrinology

This chapter covers multiple aspects of reproductive endocrinology in both male and female patients. Gender dysphoria is also included. It begins with reproductive physiology, then goes on to regulation of gonadal function. Hirsuitism, PCOS, and CAH in adults are all discussed with reference to evaluation, investigation, and treatment. Menstrual function disorders are described, as is menopause and hormone replacement therapy regimens. Contraception and emergency contraception are discussed. Male hypogonadism, androgen replacement therapy, gynaecomastia, and testicular tumours are all evaluated, alongside erectile dysfunction. The investigation and management of male and female infertility are both described, alongside fertility preservation and the induction of ovulation.

Changes in anthropometric characteristics, androgen and estrogen levels during correction of male hypogonadism with testosterone or hCG: results of a retrospective comparative study

Background: The use of testosterone replacement therapy (TRT) is widespread. Despite the positive changes, such as: an increase in testosterone levels, an improvement in erectile function and an increase in libido, it is possible to develop a negative manifestation — hyperestrogenism. To date, there are no studies assessing the prevalence of hyperestrogenism in the presence of TRT.Aim: To study the reliability of an increase in total testosterone and estradiol levels and changes in total weight, body mass index (BMI), waist circumference (WC) and hips (OB), depending on the type of TRT and hCG therapy.Materials and methods: For retrospective analysis, the medical records of patients with baseline testosterone deficiency and normal estradiol levels, who were prescribed TRT or hCG therapy, were selected. The patients were divided into 3 groups depending on the form of TRT and hCG therapy. The level of testosterone, estradiol, sex hormone binding globulin (SHBG), weight, OT, OB, BMI in each group was assessed 2 times — before the appointment of treatment and at different periods of treatment, for example, after 3–6–9 and 12 months. Most of the patients had a period of monitoring these parameters before the appointment of TRT or hCG therapy and after 6 months.Results: The increase in the levels of total testosterone and estradiol against the background of TRT in the total sample was 109.6% and 111.3%, respectively. In each group, increases in total testosterone and estradiol levels were significant, p ≤ 0.001. The level of total testosterone to physiological values increased only in the 2-nd group — reaching the average-normal, recommended levels, from 8.7 ± 0.5 (2.5) to 16 ± 2 (10). The maximum rises in total testosterone, as well as estradiol, were noted in the 1st group, from 9.5 ± 0.72 nmol / L (3) to 24.9 ± 2.7 nmol / L (11.62)) and with 24.19 ± 2 (8.5) to 58.1 ± 4 (18.1), respectively. TRT, like hCG therapy, promotes an increase in the level of estradiol, which was demonstrated in all groups, and not only in group 1-st: in group 2-nd from 28.1 ± 2.3 (11.3) to 55 ± 4 (20) and in the 3-rd group from 27.1 ± 2.5 (10.5) to 55.8 ± 4.6 (19.6). On average for the entire sample, from 26.6 ± 1.32 (10.2) to 56.2 ± 2.5 (19). Weight loss on TRT was significant only in the 2-nd group, and in all parameters — weight, BMI, waist and hip circumference. In the 3-rd group, BMI, WC and OB values also slightly decreased. In the 1-st group, the total weight slightly increased, while the BMI did not change, as did the OB value, and the OT value decreased slightly.Conclusion: TRT significantly increases the levels of total testosterone and estradiol, contributing to the normalization of testosterone levels, as in the 2-nd group, or the development of supraphysiological levels of total testosterone and hyperestrogenism, as in the 1st and 3-rd groups. Given that there is a strong belief that TRT leads to significant weight loss, our study confirmed this statement only in the 2-nd group.

Non-alcoholic steatohepatitis in patients with endocrine pathology. Review

Non-alcoholic steatohepatitis (NASH) is a subtype of non-alcoholic fatty liver disease (NAFLD), which in the absence of treatment can progress to the development of cirrhosis and hepatocellular carcinoma, as well as to increased mortality associated with these diseases. The main risk factors for the development of NAFLD and NASH are the presence of insulin resistance and obesity. Quite often NAFLD and NASH are associated with so-called extrahepatic manifestations, such as obstructive sleep apnea, hypertension, dyslipidemia, intestinal dysbiosis, genetic predisposition, sedentary lifestyle and consumption of certain foods. However, NAFLD and NASH are also associated with some endocrine diseases and conditions, including type 2 diabetes, polycystic ovary syndrome, hypothyroidism, male hypogonadism, growth hormone deficiency or excess, hypercortisolism, vitamin D or prolactin deficiency. In many of these diseases, the key pathophysiological mechanism is insulin resistance. This review considers the putative pathophysiological mechanisms that play an important pathogenetic role in the development of NASH in these endocrine disorders.Unfortunately, our understanding of the pathophysiology of NAFLD in various endocrinopathies is far from complete. In addition, the natural course of NAFLD due to endocrine disorders compared to the course and consequences of “primary” NAFLD is still poorly understood. Therefore, in the coming years, further research into the pathophysiology and clinical features of NASH will be important to better understand the relationship between different endocrinopathies and NAFLD, which will help improve the treatment of this pathology.