Azoospermia, defined as the absence of sperm in the ejaculate, is a well-documented consequence of exogenous testosterone (ET) and anabolic-androgenic steroid (AAS) use. These agents suppress the hypothalamic-pituitary-gonadal (HPG) axis, leading to reduced intratesticular testosterone levels and impaired spermatogenesis. This review examines the pathophysiological mechanisms underlying azoospermia and outlines therapeutic strategies for recovery. Azoospermia is categorized into pretesticular, testicular, and post-testicular types, with a focus on personalized treatment approaches based on the degree of HPG axis suppression and baseline testicular function. Key strategies include discontinuing ET and monitoring for spontaneous recovery, particularly in patients with shorter durations of ET use. For cases of persistent azoospermia, gonadotropins (human chorionic gonadotropin [hCG] and follicle-stimulating hormone [FSH]) and selective estrogen receptor modulators (SERMs), such as clomiphene citrate, are recommended, either alone or in combination. The global increase in exogenous testosterone use, including testosterone replacement therapy and AAS, underscores the need for improved management of associated azoospermia, which can be temporary or permanent depending on individual factors and the type of testosterone used. Additionally, the manuscript discusses preventive strategies, such as transitioning to short-acting testosterone formulations or incorporating low-dose hCG to preserve fertility during ET therapy. While guidelines for managing testosterone-related azoospermia remain limited, emerging research indicates the potential efficacy of hormonal stimulation therapies. However, there is a notable lack of well-structured, controlled, and long-term studies addressing the management of azoospermia related to exogenous testosterone use, highlighting the need for such studies to inform evidence-based recommendations.
Humans ; Azoospermia/therapy* ; Male ; Testosterone/therapeutic use* ; Anabolic Agents/adverse effects* ; Clomiphene/therapeutic use* ; Chorionic Gonadotropin/therapeutic use* ; Follicle Stimulating Hormone/therapeutic use* ; Spermatogenesis/drug effects* ; Androgens/adverse effects*

Testosterone affects several organs in the body and is very important for male well-being. Aging men with late-onset hypogonadism (LOH) experience physiologic, psychiatric, and sexual symptoms related to a decline in the serum concentration of testosterone with age. However, it is well-known that the extent of the decline in testosterone concentration does not correlate with the severity of LOH-related symptoms. Therefore, it is difficult to diagnose and treat patients with LOH. In addition, the symptoms, response to testosterone replacement therapy (TRT), and medical insurance coverage differ among ethnicities and countries. The evaluation of testosterone is essential for the diagnosis and treatment of LOH. The effects of testosterone are determined not only by the serum testosterone concentration but also by the androgen receptor sensitivity. A low number of glutamine repeats is indicative of high androgenic activity, and the number shows ethnicity-related differences (fewer in African American than in Caucasian people and more in East Asian people). The diagnosis of LOH is typically made using subjective symptoms and the serum testosterone concentration. The Aging Male Symptoms scale is widely used to evaluate the symptoms. The normal range of total testosterone concentration varies around the world; therefore, clinicians should follow the guidelines of their regional academic society. The principal treatment for LOH is TRT. There are many types of TRT and other treatment strategies are also available. Thus, physicians should treat LOH according to each patient's situation, considering related disorders, such as diabetes, osteoporosis, metabolic syndrome, and depression.
Humans ; Male ; Hypogonadism/drug therapy* ; Testosterone/blood* ; Hormone Replacement Therapy/methods* ; Japan ; Age of Onset ; Aging ; Aged ; Androgens/therapeutic use*

INTRODUCTION: Rehabilitation medicine in a tertiary care hospital involves attending to many patients affected by intensive care unit (ICU)-associated weakness (ICU-AW) and hospital-associated deconditioning (HAD). These conditions contribute to poor long-term functional outcomes and increased mortality. We explored the role of short-term adjunctive androgen therapy in this group of patients in improving the rehabilitative outcomes. METHODS: This was a retrospective analysis of five patients with either ICU-AW or HAD who were given testosterone replacement therapy (TRT) or oxandrolone for a total of 2 weeks during the period from April to November 2020 was undertaken. During the 2-week trial period, the subjects underwent standard rehabilitation therapy. RESULTS: Grip strength was used as the primary outcome measure, and the mean improvement was 4.2 kg (+24.9%), which is encouraging in a 2-week timeframe. This was matched with good functional recovery in terms of distance ambulated and less assistance needed for ambulation. Sex hormone analysis was also done before initiation of TRT, and it showed that four out of five of the subjects were biochemically hypogonadal. None of the subjects dropped out or experienced any significant adverse events over the 2-week trial period. All the subjects except one improved to full independence at 3 months post-discharge. CONCLUSION TRT has the potential to be used as a useful adjunct to standard rehabilitation in enhancing functional recovery in critically ill patients. A multidisciplinary approach would ensure that suitable patients benefit from optimal nutrition, optimal rehabilitation and synergistic testosterone therapy in a clinically sound and resource-efficient fashion.
Humans ; Testosterone/therapeutic use* ; Retrospective Studies ; Male ; Hormone Replacement Therapy/methods* ; Intensive Care Units ; Singapore ; Middle Aged ; Muscle Weakness/drug therapy* ; Aged ; Hospitals, General ; Hand Strength ; Androgens/therapeutic use* ; Treatment Outcome ; Critical Illness/rehabilitation* ; Female ; Recovery of Function

OBJECTIVE: To observe the therapeutic effect of governor vessel moxibustion combined with wenyang yiqi qiwei decoction on erectile dysfunction (ED) with spleen-kidney deficiency and to explore the possible mechanism. METHODS: A total of 130 ED patients with spleen-kidney deficiency were randomized into an observation group (65 cases, 2 cases dropped off) and a control group (65 cases, 3 cases dropped off). The control group was given wenyang yiqi qiwei decoction orally, one dose daily. On the basis of the treatment in the control group, governor vessel moxibustion was applied from Dazhui (GV 14) to Yaoshu (GV 2) in the observation group, 110 min a time, once a day. The treatment of 4 weeks was required in both groups. Before and after treatment, 5-question international index of erectile function (IIEF-5) score, erection quality scale (EQS) score, erectile hardness assessment (EHS) score, TCM syndrome score, serum testosterone (T) level and vascular endothelial function indexes (prostaglandin I2 [PGI2], endothelin-1 [ET-1] and nitric oxide [NO] levels) were observed respectively, and the clinical efficacy was evaluated in both groups. RESULTS: After treatment, the scores of IIEF-5, EQS, EHS and serum levels of T, PGI2, NO were increased compared before treatment (P<0.01), the TCM syndrome scores and serum ET-1 levels were decreased compared before treatment (P<0.01) in the two groups; the scores of IIEF-5, EQS, EHS and serum levels of T, PGI2, NO in the observation group were higher than those in the control group (P<0.01, P<0.05), the TCM syndrome score and serum ET-1 level were lower than those in the control group (P<0.01, P<0.05). The total effective rate was 88.9% (56/63) in the observation group, which was superior to 74.2% (46/62) in the control group (P<0.05). CONCLUSION Governor vessel moxibustion combined with wenyang yiqi qiwei decoction can improve the erectile function and increase the erection hardness and quality in ED patients with spleen-kidney deficiency, its mechanism may relate to improving serum T level and vascular endothelial function.
Humans ; Male ; Administration, Oral ; Drugs, Chinese Herbal/therapeutic use* ; Erectile Dysfunction/therapy* ; Kidney/pathology* ; Kidney Diseases/complications* ; Moxibustion ; Spleen/pathology* ; Splenic Diseases/complications* ; Testosterone/blood* ; Combined Modality Therapy

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Transmasculine individuals, considering whether to undergo total hysterectomy with bilateral salpingectomy, have the option to have a concomitant oophorectomy. While studies have evaluated hormone changes following testosterone therapy initiation, most of those patients have not undergone oophorectomy. Data are currently limited to support health outcomes regarding the decision to retain or remove the ovaries. We performed a retrospective chart review of transmasculine patients maintained on high-dose testosterone therapy at a single endocrine clinic in Vancouver, British Columbia, Canada. Twelve transmasculine individuals who underwent bilateral oophorectomy and had presurgical and postsurgical serum data were included. We identified 12 transmasculine subjects as controls, who were on testosterone therapy and did not undergo oophorectomy, but additionally matched to the first group by age, testosterone dosing regimen, and body mass index. There was a statistically significant decrease in the estradiol levels of case subjects postoophorectomy, when compared to presurgical estradiol levels (P = 0.02). There was no significant difference between baseline estradiol levels between control and case subjects; however, the difference in estradiol levels at follow-up measurements was significant (P = 0.03). Total testosterone levels did not differ between control and case subjects at baseline and follow-up (both P > 0.05). Our results demonstrate that oophorectomy further attenuates estradiol levels below what is achieved by high-dose exogenous testosterone alone. Correlated clinical outcomes, such as impacts on bone health, were not available. The clinical implications of oophorectomy versus ovarian retention on endocrinological and overall health outcomes are currently limited.
Female ; Humans ; Testosterone/therapeutic use* ; Retrospective Studies ; Ovariectomy ; Hysterectomy/methods* ; Estradiol

Benign prostatic hyperplasia (BPH) is a chronic male disease characterized by the enlarged prostate. Celtis chosenianaNakai (C. choseniana) is medicinally used to alleviate pain, gastric disease, and lung abscess. In this study, the effect of C. choseniana extract on BPH was investigated using testosterone-induced rats. Sprague Dawley rats were divided into five groups: control, BPH (testosterone 5 mg·kg^-1), Fina (finasteride 2 mg·kg^-1), and C. choseniana (50 and 100 mg·kg^-1). After four weeks of TP treatment with finasteride or C. choseniana, prostate weights and DHT levels were measured. In addition, the prostates were histopathologically examined and measured for protein kinase B (Akt)/nuclear factor-κB (NF-κB)/AR signaling, proliferation, apoptosis, and autophagy. Prostate weight and epithelial thickness were reduced in the C. choseniana groups compared with that in the BPH group. The extract of C. choseniana acted as a 5α reductase inhibitor, reducing DHT levels in the prostate. Furthermore, the extract of C. choseniana blocked the activation of p-Akt, nuclear NF-κB activation and reduced the expression of AR and PSA compared with BPH. Moreover, the expression of Bax, PARP-1, and p53 increased, while the expression of bcl-2 decreased. The present study demonstrated that C. choseniana extract alleviated testosterone-induced BPH by suppressing 5α reductase and Akt/NF-κB activation, reducing AR signaling and inducing apoptosis and autophagy in the prostate. These results suggested that C. choseniana probably contain potential herbal agents to alleviate BPH.
Animals ; Cholestenone 5 alpha-Reductase/metabolism* ; Finasteride/adverse effects* ; Male ; NF-kappa B/genetics* ; Plant Extracts/therapeutic use* ; Prostatic Hyperplasia/drug therapy* ; Proto-Oncogene Proteins c-akt/genetics* ; Rats ; Rats, Sprague-Dawley ; Receptors, Androgen/metabolism* ; Testosterone ; Ulmaceae/metabolism*

The relationship between androgen and prostate cancer treatment has plagued the field of urologic oncology. To investigate the efficacy and safety of bipolar androgen therapy (BAT) followed by immune checkpoint inhibitor therapy in patients with metastatic castration resistant prostate cancer (mCRPC). In August 2020, Beijing Hospital conducted an investigator-initiated study: Bipolar androgen therapy followed by immune checkpoint inhibitor therapy in metastatic castration resistant prostate cancer. Up to now, the study has included 4 patients who completed the entire cycle of treatment. The mean age of the patients was 74.5 (68 to 82) years old, the mean prostate-specific antigen (PSA) was 20.8 (9.9 to 8.36) μg/L, the mean testosterone was 0.50 (0.00 to 1.81) μg/L, and the Gleason score were 10 and 9, 7, 7 respectively. The pain scale score before treatment was 1.5 (1 to 2). In this study, 4 patients completed the entire cycle of treatment, and the treatment effect of the patients showed great heterogeneity. PSA in case 1 decreased from 24.0 μg/L to 0.47 μg/L, testosterone increased from 0.175 6 μg/L to 2.62 μg/L. PSA in case 2 increased from 9.939 μg/L to 168.536 μg/L, and testosterone increased from 0.0 μg/L increased to 2.85 μg/L. PSA increased from 13.31 μg/L to 39.278 μg/L in case 3, testosterone increased from 0.0 μg/L to 2.54 μg/L. and PSA increased from 36.0 μg/L to 350.2 μg/L in the case 4, testosterone increased from 1.81 μg/L to 3.85 μg/L. Except for one patient who showed significant PSA remission, the PSA levels of the remaining three patients remained high overall. There were no adverse reactions reported in 4 patients. In the follow-up, case 1 continued to use PD-1 monoclonal antibody (median progression free survival time was 10 months). Two patients who had previously been resistant to enzalutamide received enzalutamide again after the whole cycle of treatment, and their PSA decreased again, which indicated that the patient was sensitive to enzalutamide again. BAT had a certain therapeutic effect on mCRPC patients, and the safety was controllable. Its tumor control effect still needed long-term follow-up verification in large-sample clinical trials. BAT has a certain therapeutic effect on mCRPC patient, especially the resensitivity of tumors to enzalutamide can be restored. Immune checkpoint inhibitors may have therapeutic potential in patients with prostate cancer treated with BAT and enzalutamide.
Aged ; Aged, 80 and over ; Androgens/therapeutic use* ; Humans ; Immune Checkpoint Inhibitors ; Male ; Nitriles/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms, Castration-Resistant/drug therapy* ; Testosterone/therapeutic use* ; Treatment Outcome

OBJECTIVE: To explore the effect of curcumin on the insulin receptor substrate 1 (IRS1)/phosphatidylinositol-3-kinase (PI3K)/endometrial expression of glucose 4 (GLUT4) signalling pathway and its regulator, phosphatase and tensin homolog (PTEN), in a rat model of polycystic ovarian syndrome (PCOS). METHODS: PCOS model was induced by letrozole intragastric administration. Sprague-Dawley rats were randomized into 4 groups according to a random number table: (1) control group; (2) PCOS group, which was subjected to PCOS and received vehicle; (3) curcumin group, which was subjected to PCOS and treated with curcumin (200 mg/kg for 2 weeks); and (4) curcumin+LY294002 group, which was subjected to PCOS, and treated with curcumin and LY294002 (a specific PI3K inhibitor). Serum hormone levels (17 β-estradiol, follicle stimulating hormone, luteinizing hormone, progesterone, and testosterone) were measured by enzyme linked immunosorbent assay, and insulin resistance (IR) was assessed using the homeostasis model assessment of IR. Ovarian tissues were stained with haematoxylin and eosin for pathological and apoptosis examination. Expression levels of key transcriptional regulators and downstream targets, including IRS1, PI3K, protein kinase B (AKT), GLUT4, and PTEN, were measured via reverse transcription polymerase chain reaction and Western blot, respectively. RESULTS: The PCOS group showed impaired ovarian morphology and function. Compared with the PCOS group, curcumin treatment exerted ovarioprotective effects, down-regulated serum testosterone, restored IR, inhibited inflammatory cell infiltration in ovarian tissues, decreased IRS1, PI3K, and AKT expressions, and up-regulated GLUT4 and PTEN expressions in PCOS rats (P<0.05 or P<0.01). In contrast, IRS1, PI3K, AKT, and PTEN expression levels were not significantly different between PCOS and curcumin+LY294002 groups (P>0.05). CONCLUSION The beneficial effects of curcumin on PCOS rats included the alteration of serum hormone levels and recovery of morphological ovarian lesions, in which, PTEN, a new target, may play a role in regulating the IRS1/PI3K/GLUT4 pathway.
Animals ; Female ; Humans ; Rats ; Cell Proliferation ; Curcumin/therapeutic use* ; Follicle Stimulating Hormone ; Glucose ; Hyperandrogenism ; Insulin Receptor Substrate Proteins/metabolism* ; Insulin Resistance ; Ovarian Cysts ; Ovarian Neoplasms ; Phosphatidylinositol 3-Kinase/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Polycystic Ovary Syndrome/drug therapy* ; Proto-Oncogene Proteins c-akt/metabolism* ; Rats, Sprague-Dawley ; Testosterone

OBJECTIVE: Although the protective effects of Momordica charantia L. (MC) extract on chemical-induced testicular damage have been studied, the preventive effects of MC extract on functional proteins in the epididymis under chronic stress have never been reported. This study investigated the protective effects of MC fruit extract on protein secretion, especially tyrosine-phosphorylated proteins, in the epididymis of rats exposed to chronic unpredictable stress (CUS). METHODS: Total phenolic compounds (TPC), total flavonoid compounds (TFC) and antioxidant capacities of MC extract were measured. Adult male rats were divided into 4 groups: control group, CUS group, and 2 groups of CUS that received different doses of MC extract (40 or 80 mg/kg). In treated groups, rats were given MC daily, followed by induction of CUS (1 stressor was randomly applied from a battery of 9 potential stressors) for 60 consecutive days. Plasma corticosterone and testosterone levels were analyzed after the end of experiment. Expressions of heat-shock protein 70 (HSP-70) and tyrosine-phosphorylated proteins present in the fluid of the head and tail of the epididymis were quantified using Western blot. RESULTS: MC extract contained TPC of (19.005 ± 0.270) mg gallic acid equivalents and TFC of (0.306 ± 0.012) mg catechin equivalents per gram, and had 2,2-diphenyl-1-picrylhydrazyl antioxidant capacity of (4.985 ± 0.086) mg trolox equivalents per gram, radical 50% inhibitory concentration of (2.011 ± 0.008) mg/mL and ferric reducing antioxidant power of (23.697 ± 0.819) µmol Fe(II) per gram. Testosterone level in the epididymis was significantly increased, while the corticosterone level was significantly improved in groups treated with MC extract, compared to the CUS animals. Particularly, an 80 mg/kg dose of MC extract prevented the impairments of HSP-70 and tyrosine-phosphorylated protein expressions in the luminal fluid of the epididymis of CUS rats. CONCLUSION MC fruit extract had antioxidant activities and improved the functional proteins secreted from the head and tail of the epididymis. It is possible to develop the MC fruit extract as a male fertility supplement for enhancing functional sperm maturation in stressed men.
Male ; Rats ; Animals ; Antioxidants/pharmacology* ; Tyrosine/metabolism* ; Plant Extracts/therapeutic use* ; Corticosterone ; Seeds ; Testosterone ; Fruit/metabolism*