Serum Testosterone Levels Research Articles

7472 Estrogen Monotherapy for Testosterone Suppression in Gender Diverse Patients

Abstract Disclosure: C. Zhou: None. Q. Jones: None. S. Kokosa: None. C. Kelley: None. Background: For gender diverse individuals assigned male at birth (AMAB), gender-affirming hormone therapy consists of estrogen in combination with anti-androgen medications. Exogenous estrogen use results in the development of feminine secondary sex characteristics while indirectly decreasing testosterone. Anti-androgens such as spironolactone, leuprolide, finasteride, or dutasteride work to further suppress testosterone with successful suppression levels <50ng/dL. However, use of these agents increases the risk of adverse side effects like hyperkalemia, polyuria, and orthostatic hypotension, thus is not suitable for everyone. Anecdotally, estrogen monotherapy has been sufficient in reducing testosterone levels to goal in some patients, however at this time there are no known studies which evaluate estrogen monotherapy and suppression of testosterone. The purpose of this study is to retrospectively review estrogen formulations and dosages in patients who have adequate testosterone suppression in the absence of anti-androgen medications. Methods: The study was a retrospective chart review of adult patients ages 18- 84.99 AMAB receiving gender-affirming estrogen between 9/2020 and 12/2023 seen within an endocrine clinic at a single academic institution. Patients younger than 18, those receiving anti-androgen medications, and those with history of orchiectomy were excluded from the study. Charts were reviewed for estrogen formulations and dosages and total serum testosterone levels. Retrospective chart review will continue with additional data expected in 2024. Results: Ten patients between the ages of 19-81 met the inclusion criteria. Of these, 7 patients identified as transfeminine and 3 identified as nonbinary. The 3 patients who identified as non-binary were not included in analysis as their treatment goals may not align with full feminization or testosterone suppression (total serum testosterone <50ng/dL). Testosterone suppression from estrogen monotherapy was achieved in 100% (n=7) of the transfeminine patients when serum estradiol was >100pg/mL. In those who achieved testosterone suppression, 5 used injectable formulations (estradiol valerate 4-6mg weekly) and 2 used transdermal patches (range of estradiol from 0.2mg twice weekly to 0.3mg three times weekly). Conclusions: Estrogen monotherapy may be effective in suppressing testosterone without the need for anti-androgen medications. So far, this was noted most commonly with use of injectable estrogen formulations. A limitation of the study is the small sample size, however ongoing data collection is anticipated. Additional research evaluating estrogen monotherapy and testosterone suppression is needed and has potentially significant implications for simplified treatment protocols for transfeminine patients. Presentation: 6/2/2024

7472 Estrogen Monotherapy for Testosterone Suppression in Gender Diverse Patients

Abstract Disclosure: C. Zhou: None. Q. Jones: None. S. Kokosa: None. C. Kelley: None. Background: For gender diverse individuals assigned male at birth (AMAB), gender-affirming hormone therapy consists of estrogen in combination with anti-androgen medications. Exogenous estrogen use results in the development of feminine secondary sex characteristics while indirectly decreasing testosterone. Anti-androgens such as spironolactone, leuprolide, finasteride, or dutasteride work to further suppress testosterone with successful suppression levels <50ng/dL. However, use of these agents increases the risk of adverse side effects like hyperkalemia, polyuria, and orthostatic hypotension, thus is not suitable for everyone. Anecdotally, estrogen monotherapy has been sufficient in reducing testosterone levels to goal in some patients, however at this time there are no known studies which evaluate estrogen monotherapy and suppression of testosterone. The purpose of this study is to retrospectively review estrogen formulations and dosages in patients who have adequate testosterone suppression in the absence of anti-androgen medications. Methods: The study was a retrospective chart review of adult patients ages 18- 84.99 AMAB receiving gender-affirming estrogen between 9/2020 and 12/2023 seen within an endocrine clinic at a single academic institution. Patients younger than 18, those receiving anti-androgen medications, and those with history of orchiectomy were excluded from the study. Charts were reviewed for estrogen formulations and dosages and total serum testosterone levels. Retrospective chart review will continue with additional data expected in 2024. Results: Ten patients between the ages of 19-81 met the inclusion criteria. Of these, 7 patients identified as transfeminine and 3 identified as nonbinary. The 3 patients who identified as non-binary were not included in analysis as their treatment goals may not align with full feminization or testosterone suppression (total serum testosterone <50ng/dL). Testosterone suppression from estrogen monotherapy was achieved in 100% (n=7) of the transfeminine patients when serum estradiol was >100pg/mL. In those who achieved testosterone suppression, 5 used injectable formulations (estradiol valerate 4-6mg weekly) and 2 used transdermal patches (range of estradiol from 0.2mg twice weekly to 0.3mg three times weekly). Conclusions: Estrogen monotherapy may be effective in suppressing testosterone without the need for anti-androgen medications. So far, this was noted most commonly with use of injectable estrogen formulations. A limitation of the study is the small sample size, however ongoing data collection is anticipated. Additional research evaluating estrogen monotherapy and testosterone suppression is needed and has potentially significant implications for simplified treatment protocols for transfeminine patients. Presentation: 6/2/2024

8661 A case of post-menopausal female with virilization due to Sertoli-Leydig cell ovarian tumor recurring in contralateral ovary 8 years later

Abstract Disclosure: M.S. Maharaul: None. J.L. Miller: None. Introduction: Sertoli-Leydig cell tumors (SLCTs) are rare androgen-secreting tumors of the ovaries, accounting for less than 0.5% of all ovarian tumors. Their incidence peaks in the second to third decade of life. New onset of severe hyperandrogenism with virilization in postmenopausal women is exceedingly rare, and the three most frequent causes are ovarian tumors, ovarian hyperthecosis and adrenal androgen producing tumors. We report one such case of ovarian androgen producing tumor which was further complicated by recurrence in the contralateral ovary. Case: A 66-year-old woman presented for evaluation of hyperandrogenism. Physical examination revealed evidence of virilization and clitoromegaly. Laboratory workup was remarkable for total serum testosterone level of 367 ng/dL with normal dehydroepiandrosterone sulfate and cortisol levels. A computerized scan of abdomen did not show any adrenal masses. Transvaginal ultrasound revealed uterine myomas but did not show any ovarian pathology. She underwent selective vein catheterization of her adrenal glands as well as ovaries and was noted to have right ovary secreting 3,982 ng/dL of testosterone whereas all other samples had total testosterone levels < 200 ng/dL. She underwent right salpingo-oophorectomy. Histopathologic examination revealed a 2.2 cm well differentiated Sertoli-Leydig cell tumor confined to the ovary; the fallopian tube was negative for tumor. Six weeks later, her serum total testosterone level was 18 ng/dL. 8 years later, she returns with recurrent symptoms of hyperandrogenism. Repeat workup revealed a total testosterone level of 662 ng/dL. A computerized scan of abdomen and transvaginal ultrasound revealed an unremarkable uterus and left ovary. Magnetic resonance imaging of the pelvis was done that showed a 1.2 cm enhancing mass in the left ovary. She then underwent left salpingo-oophorectomy and supracervical hysterectomy. Histopathologic examination revealed a 1.5 cm Sertoli-Leydig-cell tumor of the left ovary, the fallopian tube was negative for tumor. Six weeks later, her serum total testosterone level was 24 ng/dL and she felt significant improvement in her symptoms. Conclusion: We present an interesting case of virilization in a post-menopausal female due to Sertoli-Leydig cell tumor that resolved after unilateral oophorectomy but recurred 8 years later in the contralateral ovary with resolution after completion oophorectomy. Presentation: 6/2/2024

7883 Atypical Presentation of Macroprolactinoma: Discordantly Low Serum Prolactin and Therapeutic Challenges

Abstract Disclosure: S. Hossain: None. M.S. Hossain: None. B. Gautam: None. S.C. Kumar: None. H. Liao: None. D.S. Rosenthal: None. Introduction: Pituitary tumors are categorized as microadenomas (<1 cm) and macroadenomas (>1 cm) with prolactinomas being one of the most common causes. The mean prevalence of prolactinomas is 10 per 100,000 in men and 30 per 100,000 in women. Serum prolactin levels corresponds to the size of the prolactinoma and any discrepancy should be treated with caution as that may indicate co-existence of pluripotent cells. We present a patient who presented with visual field defect and headaches, found to have a pituitary macroadenoma with discordantly low serum prolactin level compared to the size of adenoma, prompting a change in the treatment course. Case Presentation: A 42 year old male with no past medical history was seen as an endocrinology consult requested by neurosurgery for frequent headaches and visual problems for 1 year. Vital signs were normal, with negative orthostatic drop of blood pressure. He had prominent bitemporal hemianopsia confirmed by formal visual field testing by Ophthalmology. No galactorrhea or features suggestive of acromegaly or hyperthyroidism. He complained of erectile dysfunction but appeared to have normal male secondary sexual characteristics. MRI of brain showed a suprasellar mass measuring 3.8 x 2.6 x 2.2 cm with mass effect on the optic chiasm, hypothalamus with extension and infiltration into the right cavernous sinus. Lab results showed elevated prolactin of 1343.5 ng/ml confirmed by serial dilution, low serum testosterone level of 134 ng/dl and inappropriately normal FSH and LH. Complete blood counts, comprehensive metabolic panel, TFT, ACTH, cortisol and IGF-1 were normal. Patient was started on bromocriptine and he noticed improvement in his field of vision and acuity within one week of starting therapy. He continued to show sustained improvement in vision and resolution of his headaches at the one-month mark. MRI 2 months from starting bromocriptine showed modest reduction in size of the tumor to 2.1 x 2.3 x 2.4 cm with continued mass effect on the optic chiasm. Prolactin level decreased to 69.3 ng/ml. Therefore, although there was some improvement in visual fields, surgical resection was recommended to alleviate the mass effect on the optic chiasm. Conclusion: Our case highlights the significance of identifying discrepancies between the size of a prolactinoma and serum prolactin levels. Expected prolactin level from a prolactinoma similar in size to our case would be >3000 ng/ml when ours was 1343.5ng/ml. Despite undergoing treatment and lowering of prolactin levels our patient's pituitary adenoma did not significantly reduce in size after two months of treatment with bromocriptine and the mass continued to exert pressure on the optic chiasm. This suggests possible presence of pluripotent cells in addition to prolactin-producing cells within the tumor. The recommended course of action was surgical resection of the mass. Presentation: 6/1/2024

Effect of deep testosterone reduction on the prognosis of metastatic prostate cancer with high-volume disease

ObjectiveThis study aims to investigate the correlation between serum testosterone levels after one month of treatment and prognosis in patients with high-volume disease metastatic prostate cancer (mPCa) who are undergoing combined androgen blockade therapy (CAB).MethodsThe clinical data of 199 patients with high-volume disease mPCa, diagnosed through biopsy pathology and imaging, were retrospectively analyzed from January 2010 to October 2022 in the Department of Urology at the First Affiliated Hospital of Xinjiang Medical University. Among these patients, 111 cases had a deep reduction in serum testosterone (< 0.7 nmol/l) after one month of treatment, while 88 cases did not achieve a deep reduction (≥ 0.7 nmol/l). The study utilized the Kaplan–Meier method to plot survival curves and employed the multifactor COX regression model to analyze independent risk factors. The risk factors with a significance level of P < 0.05 in the multivariate analysis were included in the nomogram prediction model. The accuracy of the model was assessed using the ROC curve and the calibration curve, while the net benefit for patients was evaluated through the decision curve analysis (DCA).ResultsThe group that achieved deep testosterone reduction(DTR) had a higher proportion of PSA < 0.2 ng/ml and a greater PSA decline rate after six months of treatment (P < 0.05). The group that achieved DTR and the group that did not achieve DTR had a progression to castration resistant prostate cancer(CRPC) time of 17.93 ± 6.68 months and 13.43 ± 6.12 months, respectively (P < 0.001). The median progression-free survival time for the 2 groups were 18 months and 12 months, respectively (P < 0.001). The median overall survival times were 57 months and 32 months, respectively (P < 0.001). The median progression-free survival times were 18, 15, and 10 months for the group that achieved DTR within 1 month, the group that achieved DTR beyond 1 month but within 1 year, and the group that did not achieve DTR within 1 year, respectively (P < 0.001), and the median survival times were 57, 45, and 26 months, respectively (P < 0.001). COX multivariate analysis revealed that a testosterone level of ≥ 0.7 nmol/l at 1 month of treatment is an independent risk factor for the progression to CRPC and prognosis in patients with high-volume disease mPCa (P < 0.05). The risk of death in patients with a testosterone level of ≥ 0.7 nmol/l at 1 month of treatment was 2.087 times higher than that of patients with a level of < 0.7 nmol/l (P < 0.05). A nomogram prediction model was developed using independent risk factors, with the area under the ROC curve (AUC) for progression-free survival (PFS) at 12, 15, 18, and 21 months being 0.788, 0.772, 0.760, and 0.739, respectively. For 3 and 5 years, the AUCs for overall survival (OS) were 0.691 and 0.624. The calibration curve demonstrated good consistency between the model’s predicted values and the actual outcomes.ConclusionPatients with high-volume disease mPCa who receive CAB treatment may experience extended progression-free survival and overall survival if their serum testosterone levels are below 0.7 nmol/l after one month of treatment. The longer it takes to achieve DTR, the worse the patient’s prognosis may be. The nomogram prediction model developed in this study demonstrates good predictive ability in assessing the progression and prognosis of high-volume disease mPCa.

Histomorphological Changes in Testis of Rats with Prolonged Exposure to Allethrin-Based Mosquito Coil Smoke.

To explore the potential adverse effects of prolonged inhalation of mosquito coil smoke on the testicular histomorphology and serum testosterone levels in rats. An experimental study. Place and Duration of the Study: Department of Anatomy, Army Medical College, National University of Medical Sciences (NUMS), Rawalpindi, Pakistan, from January to December 2020. This study was carried out on 20 male Sprague-Dawley rats, divided into control Group A (n = 10) and experimental Group B (n = 10). Rats in Group B were exposed to mosquito coil smoke (allethrin-based) for 4 hours / day for 12 weeks. After 12 weeks of exposure, serum testosterone levels and testicular morphology (seminiferous tubule diameter, germinal epithelium height, and testicular capsule thickness) were compared between the groups. Rats exposed to mosquito coil smoke showed significantly reduced serum testosterone levels (p <0.001) along with testicular histological disruption in terms of significantly dilated seminiferous tubules (p <0.001), reduced germinal epithelial height (p <0.001), and thickened testicular capsule (p <0.001), as compared to the control group. Prolonged inhalation of allethrin-based mosquito coil smoke reduced serum testosterone levels and caused testicular histological disruption in the exposed group of rats. Allethrin, Germinal epithelium, Mosquito coil, Seminiferous tubules, Testicular capsule, Testosterone, Testis.

Comparison of different processed products of Allium tuberosum Rottler for the treatment of mice asthenozoospermia.

Allium tuberosum Rottler improves sexual function and is used in the treatment of impotence and spermatorrhea. However, its chemical composition and mechanism of action remain unclear. This study investigates the chemical composition and mechanism of action of Allium tuberosum Rottler co-processed with salt and wine (GZP) in modulating testicular mitochondrial autophagy for the treatment of asthenozoospermia in mice. Adenine gavage + cyclophosphamide intraperitoneal injection was used to establish the model of asthenozoospermia, and six Allium tuberosum Rottler processed products were compared in the pharmacological efficacy for the treatment of asthenozoospermia in mice. The liquid chromatograph mass spectrometer (LC-MS) assay was performed to analyse the compositional changes in the GZP. The mechanism of GZP in the treatment of asthenozoospermia in mice was further investigated. The mitophagy was detected by transmission electron microscope (TEM) and immunofluorescence, respectively. Reactive oxygen species (ROS) were detected by probe. Protein expression was determined by Western blotting. GZP exhibited optimal therapeutic effects on asthenozoospermia in mice. It showed the best therapeutic effect in improving the total number of spermatozoa, sperm survival rate, improving sperm viability and reducing sperm deformity rate, alleviating the abnormal pathological morphology of mice testis, and increasing the serum testosterone (T), follicle-stimulating hormone (FSH) and prolactin (PRL) levels in mice. The LC-MS detection found that Allicin showed the most significant increase in GZP. Besides, GZP reduced ROS level and inhibited mitophagy in mice testicular tissues. Meanwhile, it restrained the expression of PINK1, Parkin, Light chain 3II (LC3-II)/Light chain 3I (LC3-I) and Caspase-3 proteins. GZP improves asthenozoospermia via inhibiting excessive mitophagy and protects the integrity of mitochondria by blocking the PINK1/Parkin signaling pathway. During which, the Allicin may play an important role.

Examining the Influence of the Route of Administration and Dose of Estradiol on Serum Estradiol and Testosterone Levels in Feminizing Gender-Affirming Hormone Therapy

IntroductionIndividuals may seek gender-affirming hormone therapy (GAHT) to align their physical appearance with their gender identity. Feminizing GAHT typically involves the use of estrogen. This study investigates the effect of route of administration (ROA) and dose of estradiol on estradiol (E2) and testosterone (T) levels in transfeminine individuals. MethodsWe conducted a chart review of 573 patients with an active prescription for estradiol for feminizing GAHT and serum hormone levels available. Multiple linear regression and analysis of variance were used to analyze the effect of dose and ROA of estradiol on serum E2 and T. ResultsOral estradiol was the only ROA demonstrating a linear dose-response, with each 1 mg/d increase associated with a reduction in T of 19.03 ng/dL (P = .005). Lower T levels were seen with higher doses of transdermal estradiol but a significant dose-response was not demonstrated. Intramuscular estradiol was associated with lower T and higher E2 compared to oral and transdermal ROAs (P < .001), with many achieving target hormone levels even at low doses. Higher doses of oral estradiol were associated with lower mean serum leutenizing hormone and follicle stimulating hormone levels (P < .05). ConclusionOral estradiol can be titrated to achieve a stepwise decrease in serum T. The intramuscular ROA appears to be the most potent delivery of estradiol with impact on serum hormone levels with doses on the low end of guideline-suggested ranges. Serum leutenizing hormone and follicle stimulating hormone may also help with the management of feminizing GAHT.

Fucoidan Ameliorates Testosterone-Induced Benign Prostatic Hyperplasia (BPH) in Rats.

Benign prostatic hyperplasia (BPH) is a major urological health issue for men globally. Fucoidan, a sulfated polysaccharide, displays diverse bioactivities such as anti-inflammatory, anti-tumor, antioxidant, and immunoregulatory effects. This 28-day study examined the effects of Undaria pinnatifida fucoidan on testosterone-induced BPH in rats. Forty-eight Sprague Dawley (SD) rats were randomly divided into six groups; G1- vehicle control, G2- testosterone alone BPH control group (3 mg/kg), G3- finasteride (10 mg/kg) + testosterone, G4- fucoidan (40 mg/kg) + testosterone, G5- fucoidan (400 mg/kg) + testosterone, and G6- fucoidan alone (400 mg/kg). The animals were observed for clinical signs, body weight, feed consumption, prostate weight, prostate index, and biochemical markers such as tumor necrosis factor-alpha (TNF-α), interleukin- 1β (IL-1β), prostate-specific antigen (PSA) and messenger ribonucleic acid (mRNA) expression of BCL-2-associated X protein (BAX) and B-cell lymphoma-2 (BCL-2) in serum. Testosterone and dihydrotestosterone (DHT) levels were evaluated in both serum and prostate. Fucoidan significantly prevented an increase in prostate weight and prostate index induced by testosterone. DHT levels in the prostate of the intervention groups were significantly lower than in the BPH control group (p <0.05); however, no significant difference was observed in serum levels. Similarly, a significant reduction was observed in serum and prostate testosterone levels in the intervention groups compared to the BPH control group (p <0.05). Biochemical analyses showed PSA levels were significantly lower in the fucoidan groups compared to the BPH control group (p<0.05). Although not statistically significant, fucoidan groups showed a trend of reducing IL-1β and TNF-α levels. Fucoidan demonstrated pro-apoptotic potential in its ability to decrease BCL-2 and increase BAX. Histopathological evidence revealed fewer microscopic lesions in the fucoidan groups compared to the BPH control group. The results suggest Undaria pinnatifida fucoidan can reduce testosterone-induced BPH symptoms in SD rats.

Nicotinamide mononucleotide ameliorates ionizing radiation-induced spermatogenic dysfunction in mice by modulating the glycolytic pathway.

Radiotherapy, a common cancer treatment, leads to infertility in male cancer survivors, particularly young and middle-aged patients. Nicotinamide mononucleotide (NMN), a precursor of nicotinamide adenine dinucleotide (NAD +), plays crucial roles in energy metabolism, DNA repair, and gene expression. The purpose of this study is to investigate the protective effects and underlying mechanisms of NMN against ionizing radiation (IR)-induced testicular injury and spermatogenic dysfunction in an adult male mouse model. To assess the effects of NMN, single whole-body γ-ray irradiation is used to induce testicular injury and spermatogenic dysfunction in adult male mice. NMN is orally administered at 500 mg/kg before and after IR exposure. The structural and cellular damage to the testes caused by 5 Gy γ-ray irradiation, as well as the protective effect of NMN on testicular spermatogenic dysfunction, are evaluated. The serum hormone testosterone, LH, and FSH levels, as well as testicular NAD +, lactate, and pyruvate levels, are detected. Furthermore, the expressions of the apoptosis-related genes Bcl-2, Bax, and Caspase-3 and the rate-limiting enzymes HK2, PKM2, and LDHA, which are potentially associated with the mechanism of injury, are examined. The results demonstrate that 5 Gy γ-ray irradiation exposure causes a decrease in the serum testosterone, LH, and FSH levels in adult male mice, as well as in the testicular NAD +, lactate, and pyruvate levels, and causes damage to the testicular structure and cells. Morphometric analysis reveal a decrease in the testis mass, seminiferous tubule diameter, and height of the germinal epithelium. The sperm quantity, motility, and testicular volume are reduced in the 5 Gy group but are restored by NMN supplementation. NMN intervention downregulates the expressions of proapoptotic genes ( Bax and Caspase-3) and upregulates the expression of an antiapoptotic gene ( Bcl- 2). Sertoli cells marker genes ( WT-1, GATA-4, SOX9, and vimentin) and glycolysis rate-limiting enzyme-encoding genes ( HK2, PKM2, LDHA) are significantly upregulated. In summary, NMN has a positive regulatory effect on testicular spermatogenic dysfunction in male mice induced by ionizing radiation. This positive effect is likely achieved by promoting the proliferation of spermatogenic cells and activating glycolytic pathways. These findings suggest that NMN supplementation may be a potential protective strategy to prevent reproductive damage to male subjects from ionizing radiation.

Sulforaphane substantially impedes testicular ferroptosis in adult rats exposed to di-2-ethylhexyl phthalate through activation of NRF-2/SLC7A11/GPX-4 trajectory.

Di-2-ethylhexyl phthalate (DEHP) is a common plasticizer with a deleterious impact on testicular functionality and male fertility. Growing evidence implicates ferroptosis as one of the plausible mechanisms for DEHP-induced testicular injury. Sulforaphane (SFN) is a natural isothiocyanate displaying beneficial effects on testicular injury in several animal models. Herein, we explored the potential protective effect of SFN on testicular ferroptosis and toxicity evoked by DEHP. Adult male Wistar rats were equally distributed into three groups (n = 6/group): (i) CON group; (ii) DEHP group, received DEHP (2g/kg PO) for 4weeks; and (iii) DEHP + SFN group, received SFN (10mg/kg, PO) 1week prior to DEHP then concurrently with DEHP for further 4weeks. Compared to CON group, exposure to DEHP caused testicular atrophy, deteriorated testicular architecture, testicular fibrosis, reduced sperm count and motility, higher sperm deformity, and declined serum testosterone level. All these abnormalities were ameliorated by SFN preconditioning. Additionally, pretreatment with SFN reversed the increased aromatase level and upregulated the steroidogenic markers in testes of DEHP-exposed rats. SFN pretreatment also counteracted DEHP-induced oxidative stress and boosted the total antioxidant capacity in testicular tissue via activation of the nuclear factor erythroid 2-related factor 2 (NRF-2) and its downstream target, hemeoxygenase-1 (HO-1). Moreover, SFN preconditioning mitigated DEHP-induced ferroptosis through up-surging SLC7A11, GPX-4, and GSH, while suppressing iron overload and ACSL4-induced lipid peroxidation in testicular tissue of rats. These findings may nominate SFN as a promising protective intervention to alleviate testicular ferroptosis associated with DEHP exposure through activation of NRF-2/SLC7A11/GPX-4 trajectory.

RELATIONSHIP BETWEEN HYPOGONADISM AND SERUM TESTOSTERONE LEVELS IN CHRONIC LIVER DISEASE

Background: Men with extensive chronic liver disease usually have low levels of testosterone in the serum. This study looked at the relationship between hypogonadism and low serum testosterone levels in patients with chronic liver disease. Methods: This retrospective study was conducted at Central Park Teaching Hospital, Lahore from Jan 2022 to Jan 2024, on patients between 5 to 60 years of age. After approval from ERB and permission from the authorities, records were retrieved. Two hundred records of men with hepatic cirrhosis and verified hypogonadism were divided into alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD), while records of 150 men as control group were include in the study. Patients’ data for ‘Sex Hormone Binding Globulin (SHBG)’ and ‘total testosterone’ were collected and entered into MS Excel file. Using SPSS-22 independent Student’s t-test was applied for statistical analysis. Results: No statistically significant variations were observed (p=0.101) in the means of SHBG across two groups but there was a statistically significant (p&lt;0.05) variation in blood serum testosterone levels between age groups. Conclusion: Hypogonadism and low levels of testosterone are strongly linked to male patients with cirrhotic liver conditions, particularly in those with ALD, while no significant impact of SHBG was found between the two groups. Significant differences were observed between patients with ALD and NAFLD in terms of testosterone levels. Pak J Physiol 2024;20(3):53–5, DOI: https://doi.org/10.69656/pjp.v20i3.1687

Involvement of Sex Hormones and Their Receptors in the Pathogenesis of Classic Kaposi's Sarcoma in Xinjiang.

This study aims to examine the expression of androgen receptor (AR) and estrogen receptor (ER) in patients with classic Kaposi's sarcoma (CKS) in Xinjiang, as well as to assess the serum levels of sex hormones in these patients. The objective is to explore potential new directions and targets for diagnosing and treating CKS in Xinjiang. The case group comprised 35 patients diagnosed with CKS who presented at our hospital from 2014 to 2021. The control group consisted of 35 patients with pyogenic granuloma (PG) who visited the hospital during the same period, selected using propensity score matching (PSM). Immunohistochemistry was used to detect AR, human herpesvirus type 8 (HHV-8), and ER in paraffin-embedded tissue samples from patients diagnosed with CKS and PG. Additionally, enzyme-linked immunosorbent assay (ELISA) was used to quantitatively measure serum sex hormone levels in the 35 patients with CKS and 35 patients with PG. AR expression was relatively weak in both the CKS and PG groups, with the PG group exhibiting a slightly stronger expression than the CKS group. Conversely, the expression of ER was significantly higher in the CKS group compared to the PG group (p < 0.05). Additionally, serum testosterone (T) levels were elevated in the CKS group, while serum estradiol (E2) levels were higher in the PG group (p < 0.05). Sex hormones and their receptors are implicated in the pathogenesis of CKS in Xinjiang. The use of ER antagonists may represent a novel avenue for research and treatment of CKS.

Variations in anterior segment parameters among different phenotypes of polycystic ovary syndrome

PurposeThe objective of this study was to evaluate anterior segment parameters across various phenotypes of polycystic ovary syndrome (PCOS), considering body mass index (BMI), serum estradiol and testosterone levels.Materials and MethodsThis prospective study included 116 women with PCOS, with each of the four distinct phenotype comprising 29 women. Additionally, 29 healthy women were included in the control group. All participants underwent comprehensive ophthalmologic examinations, including intraocular pressure (IOP) measurements. Anterior segment parameters, such as central corneal thickness (CCT), axial length (AL), aqueous depth (AD), anterior chamber depth (ACD), and lens thickness (LT) were measured using optic biometry. Endothelial cell density (ECD) was assessed using non-contact specular microscopy. The BMI was calculated, and serum levels of estradiol and testosterone were noted.ResultsIOP was found to be significantly higher (p = 0.003) and CCT was significantly thicker (p = 0.004) in all phenotypes of PCOS compared to the control group. BMI, serum estradiol and free testosterone were found to correlate with both IOP and CCT. AL, AD, ACD and LT values showed no significant differences compared to the control group. Although ECD tend to be higher in the PCOS phenotypes, this difference was not statistically significant (p > 0.05).ConclusionGiven our findings that CCT and IOP are significantly elevated in PCOS phenotypes. PCOS should be considered as an important factor when evaluating female patients for anterior segment diseases and glaucoma.

The Effects of L-Tartaric Acid on Ovarian Histostereological and Serum Hormonal Analysis in an Animal Model of Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is the most common endocrine-related reproductive disorder in women of reproductive age, accompanied by both the impairment of female fecundity and a risk of metabolic disorders. PCOS is emphasized as a worldwide concern due to its unknown etiology and lack of specific medications. The current study aimed to evaluate the effects of L-tartaric acid, an abundantly occurring compound in fruits, on the histostereological and hormonal changes caused by PCOS. Forty adult Sprague Dawley rats were randomly divided into four groups including controls (no intervention), Tartaric acid (40mg/Kg/day from day 21 onwards for 39 days), PCOS (21 days letrozole and then normal saline orally for 39 days), and PCOS + Tartaric acid. After treatments, the ovarian histostereological analysis as well as the level of reproductive hormones including luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, progesterone, and testosterone was measured. PCOS caused a significant decrease in the number of unilaminar, multilaminar, antral, and graafian follicles and increased follicular atresia (p-value < 0.001). Moreover, the weight and volume of ovarian tissue and related structures including cortex, medulla, and cysts increased significantly (p-value < 0.0001). However, corpus luteum volume was significantly decreased (p-value < 0.001). Although significant differences were found in some parameters with the control group (p-value < 0.05), the administration of tartaric acid restored the pathological effects of PCOS on the ovarian histostructure. Furthermore, tartaric acid improved the serum levels of LH, estradiol, progesterone, and testosterone (p-value < 0.05). The obtained findings may suggest tartaric acid as a novel strategy for PCOS management, although further studies are necessary.

Conditional associations of sex steroid hormones with C-reactive protein levels in American children and adolescents: evidence from NHANES 2015-2016.

The relationship between sex steroid hormones and high-sensitivity C-reactive protein(hs-CRP) levels in American children and adolescents is understudied. This research will examine this association. The study conducted a data analysis from the National Health and Nutrition Examination Survey (NHANES) 2015-2016, adjusting multiple linear regression models with R 4.2.2 and EmpowerStats. A total of 1,768 children and adolescents were surveyed. Data collection involved measurements of serum levels of testosterone, estradiol, sex hormone-binding globulin (SHBG) and hs-CRP. With the increase in testosterone, a brief rise (β=0.082, P=0.047) followed by an overall decline (β=-0.028, P=0.023) in hs-CRP was observed in the Male Prepubertal population, while a continuous decline (β=-0.002, P<0.05) was seen in the Male Pubertal group. A positive correlation (β=0.047, P<0.05) was found between testosterone and hs-CRP in the Female Prepubertal population, whereas no significant association (β=0.002, P>0.05) was detected in the Female Pubertal group. A significant inverse correlation was observed between estradiol and hs-CRP solely in the Female Pubertal group (β=-0.002, P<0.05), while no association was found in other populations. An inverse relationship between SHBG and hs-CRP was consistently noted across all groups: Male Prepubertal, Male Pubertal, Female Prepubertal, and Female Pubertal. The association between sex steroid hormones and high-sensitivity C-reactive protein (hs-CRP) levels among American children and adolescents is conditional and influenced by multiple factors.

Involvement of the AMPK Pathways in Muscle Development Disparities across Genders in Muscovy Ducks.

The differences in muscle development potential between male and female ducks lead to variations in body weight, significantly affecting the growth of the Muscovy duck meat industry. The aim of this study is to explore the regulatory mechanisms for the muscle development differences between genders. Muscovy ducks of both sexes were selected for measurements of body weight, growth traits, hormone levels, and muscle gene expression. The results show that male ducks compared to females had greater weight and growth traits (p < 0.05). Compared to male ducks, the level of serum testosterone in female ducks was decreased, and the estradiol levels were increased (p < 0.05). The RNA-seq analysis identified 102 upregulated and 49 downregulated differentially expressed genes. KEGG analysis revealed that among the top 10 differentially enriched pathways, the AMPK signaling pathway is closely related to muscle growth and development. Additionally, the mRNA and protein levels of CD36, CPT1A, LPL, and SREBP1 were increased and the P-AMPK protein level decreased in the female ducks compared to the male ducks (p < 0.05). In conclusion, muscle development potential difference between male and female ducks is regulated by sex hormones. This process is likely mediated through the activation of the AMPK pathway.

SPRY4 regulates ERK1/2 phosphorylation to affect oxidative stress and steroidogenesis in polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women of childbearing age. The role of Sprouty RTK Signaling Antagonist 4 (SPRY4) in ovarian function in PCOS was investigated herein, focusing on its regulation of ERK1/2 phosphorylation. PCOS models were established in mice using dehydroepiandrosterone (DHEA). The expression levels of SPRY4 in ovarian tissues were analyzed through RT-qPCR and immunohistochemistry. SPRY4 knockdown was achieved via lentivirus, and its effects on endocrine function, ovarian morphology, oxidative stress, and ERK1/2 phosphorylation were evaluated. Afterwards, granulosa cells were isolated and treated with DHEA and ERK2 agonist tert-Butylhydroquinone. The impacts of ERK2 activation on the regulation of SPRY4 knockdown were assessed using ELISA, fluorescent probes, western blotting, and biochemical assays. SPRY4 knockdown normalized the estrous cycle, reduced serum levels of testosterone, anti-Müllerian hormone, and luteinizing hormone/follicle-stimulating hormone ratio, and improved ovarian morphology. Additionally, SPRY4 knockdown alleviated oxidative stress by decreasing reactive oxygen species and malondialdehyde levels while increasing superoxide dismutase activity. It also restored steroidogenic enzyme expression, which were disrupted by DHEA induction. In vitro, SPRY4 knockdown enhanced granulosa cell viability and reduced ERK1/2 phosphorylation, with tert-Butylhydroquinone reversing these effects and restoring oxidative stress and steroidogenesis disruptions. Together, SPRY4 modulates ERK1/2 phosphorylation to influence oxidative stress and steroidogenesis in PCOS. Targeting SPRY4 may provide novel therapeutic avenues for improving ovarian function and managing PCOS.

The Natural HASPIN Inhibitor Coumestrol Suppresses Intestinal Polyp Development, Cachexia, and Hypogonadism in a Mouse Model of Familial Adenomatous Polyposis (ApcMin/+).

(1) Background: HASPIN kinase is involved in regulating spindle function and chromosome segregation, as well as phosphorylating histone H3 at Thr3 in mitotic cells. Several HASPIN inhibitors suppress cancer cell proliferation. It was recently reported that coumestrol from bean sprouts inhibits HASPIN, and a cultivation method for bean sprouts containing large amounts of coumestrol has been established. Here, we showed the effects of bean sprout ingestion on intestinal polyp development, cachexia, and hypogonadism in a mouse model of familial adenomatous polyposis (ApcMin/+). (2) Methods: ApcMin/+ mice were randomized into control and treatment groups. Mice in the control group were given the standard diet, while those in the treatment group were given the same standard diet with the addition of 15% bean sprouts. Treatments were commenced at 7 weeks old and analyses were performed at 12 weeks old. (3) Results: ingesting bean sprouts suppressed the development of intestinal polyps, cachexia, and hypogonadism, and also increased serum levels of testosterone in male wild-type and ApcMin/+ mice. (4) Conclusions: ingesting bean sprouts helps prevent cancer and increases serum levels of testosterone in a mouse model. These results are expected to be applicable to humans.

Evaluation of serum irisin level and severity of erectile dysfunction in diabetic males: a cross sectional prospective study

BackgroundIrisin is an exercise-induced myokine that alleviates endothelial dysfunction and reduces insulin resistance in type 2 diabetes mellitus (T2DM). The current study aimed to assess the serum level of irisin in T2DM men with erectile dysfunction (ED) compared to T2DM patients with normal erectile function and healthy controls, as well as investigate the association between serum irisin level and the severity of ED in T2DM patients.Patients and methodsA cross-sectional study was conducted on 90 males, divided into three groups: 32 T2DM patients with ED, 24 T2DM patients without ED, and 34 healthy controls. Socio-demographic characteristics and scores of the validated Arabic version of the international Index of Erectile Function-5 (ArIIEF-5), Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) were obtained. Furthermore, routine laboratory tests employed for diabetes monitoring and serum levels of total testosterone and irisin were assessed within these groups.ResultsT2DM men with ED had significantly lower serum levels of irisin and testosterone, as well as a lower ArIIEF-5 score, but their GAD-7 and PHQ-9 scores were significantly higher than those without ED or controls (p < 0.001). Among T2DM men, serum irisin levels positively associated with ArIIEF-5 scores and serum testosterone (r = 0.413, p = 0.002; r = 0.936, p < 0.001, respectively) but negatively associated with glycosylated hemoglobin levels (r = -0.377, p = 0.004). Multivariate regression analysis to predict ED in T2DM patients found that GAD-7 score was the only most significant predictor for ED (ꞵ = − 1.176, standard error = 0.062, p < 0.001).ConclusionThe current study had demonstrated that irisin positively correlated with the ArIIEF-5 and serum testosterone but negatively correlated with HbA1c in T2DM men. Nevertheless, further validation of these findings is necessary through cohort studies.