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- Hypogonadism as a Reversible Cause of Torsades de Pointes in Men. [Letter]
- CircCirculation 2018 Jul 03; 138(1):110-113
- The VEGF and PEDF levels in the follicular fluid of patients co- treated with LETROZOLE and gonadotropins during the stimulation cycle. [Journal Article]
- RBReprod Biol Endocrinol 2018 May 29; 16(1):54
- CONCLUSIONS: Opposite to observations in the mouse, we found that VEGF levels were increased and PEDF levels were decreased in the follicular fluid in patients treated with letrozole during the stimulation cycles. Further investigation is required to determine if patients treated with letrozole during the IVF stimulation protocol are at increased risk for developing OHSS as a result of these findings.
- Impact of prepubertal exposure to dietary protocatechuic acid on the hypothalamic-pituitary-testicular axis in rats. [Journal Article]
- CBChem Biol Interact 2018 Jun 25; 290:99-109
- Protocatechuic acid (PCA; 3, 4-dihydroxybenzoic acid) is a phenolic compound widely found in many edible fruits, vegetables, grape wine and plant-derived beverages. The present study investigated the...
Protocatechuic acid (PCA; 3, 4-dihydroxybenzoic acid) is a phenolic compound widely found in many edible fruits, vegetables, grape wine and plant-derived beverages. The present study investigated the impact of PCA on the hypothalamic-pituitary-testicular axis of rats orally treated with PCA during the period of prepubertal development to adulthood. Protocatechuic acid was administered to prepubertal male rats at doses of 0, 5, 10, 50 and 100 mg/kg body for 45 consecutive days. The results revealed no treatment-related changes in the body weight gain and organo-somatic indices of the hypothalamus, testes, epididymis, prostate gland and seminal vesicle in rats administered with PCA when compared with control. However, prepubertal exposure to PCA significantly enhanced antioxidant enzyme activities and glutathione level whereas it markedly decreased biomarkers of inflammation and oxidative stress in the hypothalamus, testes and epididymis of the treated rats. Protocatechuic acid significantly increased circulatory concentrations of luteinizing hormone and follicle-stimulating hormone with concomitant increase in serum and intra-testicular testosterone levels. Moreover, PCA-treated rats exhibited significant increase in marker enzymes of testicular function namely acid phosphatase, alkaline phosphatase, lactate dehydrogenase and glucose-6-phosphate dehydrogenase without statistically significant increase in spermatogenesis and sperm functional characteristics including sperm count, motility and viability. Light microscopic examination of the hypothalamus, testes and epididymis of rats treated with PCA showed histo-architectures similar to control. In conclusion, prepubertal exposure to PCA is safe and positively impacted reproductive function at sexual maturity in male rats. The observed beneficial effects of PCA is related to its anti-inflammatory and redox regulatory mechanisms.
- Attenuation of Metabolic Syndrome by EPA/DHA Ethyl Esters in Testosterone-Deficient Obese Rats. [Journal Article]
- MDMar Drugs 2018 May 24; 16(6)
- Inducing testosterone deficiency, as the standard treatment of prostate cancer, may cause metabolic disorders including insulin resistance, dyslipidemia, central obesity, cardiovascular diseases, and...
Inducing testosterone deficiency, as the standard treatment of prostate cancer, may cause metabolic disorders including insulin resistance, dyslipidemia, central obesity, cardiovascular diseases, and type 2 diabetes. This study measured responses to testosterone deficiency in high-carbohydrate, high-fat (H) diet-fed rats. We then tested whether eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) ethyl esters (Omacor) reversed these metabolic changes. Male Wistar rats (8⁻9 weeks old) were divided into eight groups with four groups fed corn starch and four groups fed H diet. For each diet, one group received diet only; one group was orchidectomized; one group was given leuprolide (gonadotrophin-releasing hormone agonist, 2 mg/kg every 4th week); and the last group was treated with leuprolide and their diet was supplemented with 3% Omacor for the last eight weeks. The protocol was for 16 weeks. Leuprolide worsened metabolic syndrome symptoms and cardiovascular function, and orchidectomy produced greater responses. In H fed leuprolide-treated rats, Omacor decreased systolic blood pressure and left ventricular diastolic stiffness, reduced infiltration of inflammatory cells and collagen deposition in the heart, and reduced lipid accumulation and inflammatory cell infiltration without improving liver damage. These results suggest that Omacor has potential to attenuate metabolic complications in prostate cancer patients with induced testosterone deprivation.
- The protective effects of alpha lipoic acid on methotrexate induced testis injury in rats. [Journal Article]
- BPBiomed Pharmacother 2018; 97:1486-1492
- Methotrexate (MTX) is frequently used in the treatment of several diseases including cancers, rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, and dermatomyositis. Previously,...
Methotrexate (MTX) is frequently used in the treatment of several diseases including cancers, rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, and dermatomyositis. Previously, chemotherapeutic agents have been reported to cause permanent azoospermia and infertility in men. Methotrexate has been also shown to damage the seminiferous tubules of the testicles, lower the sperm count, and cause genetic mutations (in DNA) in sperm. In this study, we aimed to investigate the protective effects of alpha lipoic acid (ALA) on MTX-induced testicle damage in a rat model. A total of 40 male Wistar Albino rats were used in this study. The rats were divided into four groups including 10 rats in each. The first group (control group) received only saline intraperitoneal (i.p.); the second group (ALA group) was given ALA 100 mg/kg i.p.; the third group (MTX group) received single dose MTX 20 mg/kg i.p.; and the fourth group (MTX + ALA group) received single dose MTX 20 mg/kg i.p. and ALA 100 mg/kg i.p. Malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), myeloperoxidase (MPO) levels in the testicular tissue and serum testosterone, serum total antioxidant status (TAS) and total oxidant status (TOS) levels were biochemically evaluated. Testicular tissues histopathologically evaluated. In the MTX group, the MDA, TAS and TOS levels were higher, while the SOD, CAT, GPx, MPO and serum testosterone levels decreased. Compared to the MTX group, the MDA, TAS and TOS levels were lower and the SOD, CAT, GPx, MPO and serum testosterone levels increased in the MTX + ALA group. In the histopathological examination, the mean seminiferous tubule length (MSTD), germinal epithelial cell thickness (GECT), and mean testicular biopsy score (MTBS) were found to significantly decrease in the MTX group, compared to the control group. These values were significantly higher in the MTX + ALA group, compared to the MTX group (p < 0.05). In our experimental study, MTX caused severe tissue destruction in testicles by increasing the formation of free oxygen radicals. Based on our study results, we suggest that, as a potent free radical scavenger, ALA can reduce MTX-induced testicular tissue damage thanks to its antioxidant and anti-inflammatory properties.
- Tetragonia tetragonioides (Pall.) Kuntze Regulates Androgen Production in a Letrozole-Induced Polycystic Ovary Syndrome Model. [Journal Article]
- MMolecules 2018 May 14; 23(5)
- Tetragonia tetragonioides (Pall.) Kuntze (TTK) is a medicinal plant traditionally used to treat various diseases such as diabetic, inflammatory, and female-related disorders. Polycystic ovary syndrom...
Tetragonia tetragonioides (Pall.) Kuntze (TTK) is a medicinal plant traditionally used to treat various diseases such as diabetic, inflammatory, and female-related disorders. Polycystic ovary syndrome (PCOS) is a common endocrinological disorder in women of reproductive age, and hyperandrogenism is a prominent feature of PCOS resulting in anovulation and infertility. In this study, we investigated the effects of a TTK extract on androgen generation and regulation of steroidogenic enzymes in vitro and in vivo. Human adrenocortical NCI-H295R cells were used to assess the effects of TTK extract on production of dehydroepiandrosterone and testosterone, as well as the protein expression of steroidogenic enzymes. Further, a letrozole-induced PCOS rat model was used in vivo to assess whether dietary administration of TTK extract restores normal hormones and reduces PCOS symptoms. TTK extract significantly inhibited forskolin (FOR)-induced androgen production in NCI-H295R cells and serum luteinizing hormone, testosterone, and follicular cysts, but not estradiol, were reduced in letrozole-induced PCOS rats orally administered the TTK extract. In addition, TTK extract inhibits androgen biosynthesis through the ERK-CREB signaling pathway, which regulates CYP17A1 or HSD3B2 expression. TTK extract could be utilized for the prevention and treatment of hyperandrogenism and other types of PCOS.
- First-line use of novel hormonal agents in prostate cancer: a critical appraisal. [Journal Article]
- CAClin Adv Hematol Oncol 2018; 16(4):289-295
- Castration has been the hallmark of the treatment of advanced prostate cancer for nearly a century. Conventional surgical or medical castration for the management of metastatic prostate cancer has be...
Castration has been the hallmark of the treatment of advanced prostate cancer for nearly a century. Conventional surgical or medical castration for the management of metastatic prostate cancer has been associated with an initial response rate greater than 60% to 70%, depending on the criteria employed. The median duration of the initial response is usually less than 3 to 5 years, however, depending on the extent of disease. The failure of disease to respond to castration has been associated with an increase in the production of adrenal androgens and/or the evolution of upregulated or mutated androgen receptors. Second-line hormonal treatment with adrenal inhibitors is sometimes used, but remissions usually last for less than a year. Extensive translational research has produced a series of second-line, multitargeted, hormonally active agents that inhibit androgen receptor function and/or multiple sites within the hypothalamic/pituitary/end-organ axis. Abiraterone and enzalutamide have been shown to be active in second-line or subsequent hormonal therapy for castration-resistant prostate cancer, and recent data have shown a substantial anticancer effect in initial therapy. The potential use of abiraterone and enzalutamide as initial therapy for advanced prostate cancer is the focus of this brief review, which emphasizes that new approaches should not become the standard of care until they have been validated in randomized trials. In addition, it remains unclear whether first-line treatment with chemohormones or new-generation hormones should be the current standard for all patients with newly diagnosed metastatic prostate cancer.
- Low estrogen doses normalize testosterone and estradiol levels to the female range in transgender women. [Journal Article]
- CClinics (Sao Paulo) 2018; 73:e86
- CONCLUSIONS: In our sample of transgender women, lower estrogen doses than those usually prescribed for these subjects were able to adjust the testosterone and estradiol levels to the physiological female range, thus avoiding high estrogen doses and their multiple associated side effects.
- [Low serum testosterone level does not predict bone metastasis of prostate cancer]. [Journal Article]
- ZNZhonghua Nan Ke Xue 2017; 23(3):212-216
- CONCLUSIONS: The low level of serum testosterone is closely associated with but not an independent predictor of bone metastasis of prostate cancer.
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- Androgen- and estrogen-receptor mediated activities of 4-hydroxytestosterone, 4-hydroxyandrostenedione and their human metabolites in yeast based assays. [Journal Article]
- TLToxicol Lett 2018; 292:39-45
- 4-Hydroxyandrost-4-ene-3,17-dione, also named formestane, is an irreversible aromatase inhibitor and therapeutically used as anti-breast cancer medication in post-menopausal women. Currently, no ther...
4-Hydroxyandrost-4-ene-3,17-dione, also named formestane, is an irreversible aromatase inhibitor and therapeutically used as anti-breast cancer medication in post-menopausal women. Currently, no therapeutical indication led to approval of its 17-hydroxylated analog 4-hydroxytestosterone, an anabolic steroid. However, it is currently investigated in a clinical trial for breast cancer. In context with sports doping, aromatase inhibitors are administered to reduce estrogenic side effects of misused anabolic substances or their metabolites. Therefore, both substances are prohibited in sports by the World Anti-Doping Agency (WADA). Analysis of urinary phase I and phase II metabolites showed similar results for both compounds. In the current investigation, 4-hydroxyandrost-4-ene-3,17-dione, 4-hydroxytestosterone and seven of their described urinary metabolites as well as 2α-hydroxyandrostenedione were tested in the yeast androgen screen and the yeast estrogen screen. Androgenic effects were observed for all tested substances, except for one, which showed anti-androgenic properties. With regard to the yeast estrogen screen, estrogenic effects were observed for only two metabolites at rather high concentrations, while six out of the ten substances tested showed anti-estrogenic properties. In terms of the strong androgenic effect observed for 4-hydroxytestosterone (10-8 M), 4-hydroxyandrost-4-ene-3,17-dione (10-8 M) and two more urinary metabolites, the yeast androgen assay may also be used to trace abuse in urine samples.