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*

OBJECTIVE: To comprehensively evaluate the effect of icariin in alleviating reproductive function damage (RFD) in male mice via in vitro and in vivo experiments. METHODS: We isolated Leydig cells from 60 KM male mice in vitro, and examined the toxic effect of icariin on the Leydig cells using Cell Counting Kit-8 (CCK-8). We equally randomized the mice into six groups: normal control, RFD model control (made by intraperitoneal injection of busulfan at 10 mg/kg combined with cyclophosphamide (CP) at 120 mg/kg), positive control, and low-, medium- and high-dose icariin. After modeling, we treated the mice in the positive control group with Wuziyanzong Pills and those in the low-, medium- and high-dose icariin groups by intragastrical administration of icariin at 20, 40 and 80 mg/kg-1, respectively, for 30 successive days. Then we obtained the weight and visceral coefficients of the reproductive organs, calculated the sperm count, observed the pathological changes in the testis tissue by HE staining, measured the serum testosterone (T) level by ELISA, determined the indexes of testicular oxidative stress and nitric oxide (NO) signaling pathway by colorimetric assay, and detected the expression levels of the pro-apoptotic genes Fas and Bax by qRT-PCR. RESULTS: CCK-8 assay confirmed that icariin had no toxic effect on the isolated Leydig cells of the mice, and could effectively reduce busulfan- and CP-induced cytotoxicity and promote the secretion of serum T. Icariin at 80 mg/kg significantly increased the visceral coefficient of the testis and promoted spermatogenesis (P<0.05), but had little effect on the visceral coefficient of the epididymis in the RFD model mice. Testicular histomorphometric observation revealed significantly improved testis structure, intact boundary membrane of seminiferous tubules and increased numbers of various types of spermatogenic cells of the model mice after treated with icariin. Compared with the mice in the model control group, those treated with high-dose icariin showed a significantly reduced content of malondialdehyde (MDA) (by 35.3%, P<0.01), elevated total antioxidant capacity (TAOC) and superoxide dismutase (T-SOD) activity (P<0.05), and decreased NO content and nitric oxide synthase (NOS) activity in the testis tissue (P<0.01). In addition, icariin exhibited an evident inhibitory effect on the expressions of the pro-apoptotic genes Bax and Fas. CONCLUSION Icariin can ameliorate oxidative stress-induced damage to the testicular function and protect spermatogenesis of male mice by elevating TAOC, decreasing NOS activity, inhibiting the NO level in the testis, and suppressing busulfan- and CP-induced apoptosis of testicular cells.
Animals ; Male ; Cyclophosphamide/adverse effects* ; Mice ; Busulfan/adverse effects* ; Flavonoids/pharmacology* ; Leydig Cells/drug effects* ; Oxidative Stress/drug effects* ; Testis/drug effects* ; Apoptosis/drug effects* ; Testosterone/blood*

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*

A variety of methods for testosterone replacement therapy (TRT) exist, and the major potential risks of TRT have been well established. The risk of developing polycythemia secondary to exogenous testosterone (T) has been reported to range from 0.4% to 40%. Implantable T pellets have been used since 1972, and secondary polycythemia has been reported to be as low as 0.4% with this administration modality. However, our experience has suggested a higher rate. We conducted an institutional review board-approved, single-institution, retrospective chart review (2009-2013) to determine the rate of secondary polycythemia in 228 men treated with subcutaneously implanted testosterone pellets. Kaplan-Meyer failure curves were used to estimate time until the development of polycythemia (hematocrit >50%). The mean number of pellets administered was 12 (range: 6-16). The mean follow-up was 566 days. The median time to development of polycythemia whereby 50% of patients developed polycythemia was 50 months. The estimated rate of polycythemia at 6 months was 10.4%, 12 months was 17.3%, and 24 months was 30.2%. We concluded that the incidence of secondary polycythemia while on T pellet therapy may be higher than previously established.
Adult ; Aged ; Androgens/adverse effects* ; Drug Implants ; Hematocrit ; Hormone Replacement Therapy/methods* ; Humans ; Hypogonadism/drug therapy* ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Polycythemia/epidemiology* ; Retrospective Studies ; Testosterone/adverse effects*

Aged ; Androgen Antagonists/adverse effects* ; Anticholesteremic Agents/therapeutic use* ; Cholesterol, HDL/blood* ; Cholesterol, LDL/blood* ; Humans ; Hypercholesterolemia/chemically induced* ; Lipids/blood* ; Male ; Middle Aged ; Prostatic Neoplasms/therapy* ; Retrospective Studies ; Testosterone/blood*

OBJECTIVE: To determine the mitigating effects of sodium 4-phenylbutyrate (4-PBA) on high-fat diet (HFD)-induced spermatogenesis dysfunction. METHODS: Male rats (n = 30) were randomly divided into three groups: control, HFD, and 4-PBA (HFD +4-PBA). After 13 weeks, rats were euthanized. Testes and epididymis were harvested for further analysis. Sex hormones were detected, and hematoxylin and eosin staining was performed to examine the histological changes in the testes. Semen samples were collected to evaluate sperm quality. Spermatogenic cell apoptosis was detected by TUNEL assay. RESULTS: Compared with the control group, the final body weight and body weight gain were significantly higher in HFD-fed rats, while the testicle/body weight ratios were lower (P < 0.05). In HFD-fed rats, obvious pathological changes in the testicular tissue were observed. Treatment with 4-PBA attenuated HFD-induced histological damage, ameliorated the HFD-induced decrease in serum testosterone (T), and reduced the rate of testicular cell apoptosis (P < 0.05) in obese male rats. Finally, 4-PBA significantly improved semen parameters in HFD rats (P < 0.05). CONCLUSION HFD exposure induced detrimental effects on spermatogenesis, semen quality, serum T level, and testicular cell apoptosis in rats. Treatment with 4-PBA ameliorated HFD？induced impaired spermatogenesis via inhibition of apop-tosis in rats. 4-PBA may have therapeutic value in the treatment of obesity？related impairment of spermatogenesis.
Animals ; Diet, High-Fat ; adverse effects ; Male ; Phenylbutyrates ; pharmacology ; Rats, Sprague-Dawley ; Semen Analysis ; Spermatogenesis ; drug effects ; Testis ; drug effects ; pathology ; Testosterone ; blood

OBJECTIVE: To study the effect of 6-week intensive training on renal function in rats and the mechanism of exercise-induced proteinuria. METHODS: Thirty-six male SD rats, aged 6 weeks, were divided into two groups, including a control group(C,=12)and an overtraining group(M,=24). After the rats adapted to feeding for 4 d, group C did not carry out any exercise, and the M group did 6-week of increasing load swimming, 6 days a week, once a day. Started with the load of 1%weight at the beginning of the 4 week,and gradually increased (to 6% weight). Took a single urine from both groups 30 min after the end of the training. Blood was taken from the main ventral vein, and the bilateral kidneys were to be tested. The levels of tested urine protein, microalbumin and neutrophil gelatinase associated lipocalin(NGAL) was determined by using enzyme linked immunosorbent assaytest. The content of urine creatinine was tested with alkaline picric acid method,. The serum levels of colorimetric method to determine serum creatinine and urea nitrogen were determined by colorimetric method. The expression of Nephrin in renal tissue was detected by Western blot and the radioimmunoassay was used to test serum testosterone, corticosterone and renin-angiotensin system related index. RESULTS: Compared with group C, the serum testosterone/cortisone(T/C) of group M was decreased significantly (<0.01). The urine total protein(TP), microalbumin (mAlb), microalbumin/creatinine (mAlb/CRE), NGAL, blood urea nitrogen (BUN) and serum creatinine(SCr) were increased significantly (<0.01). The abnormality of glomerular structure was obvious, and the paller scores were higher. The protein expression of Nephrin was obviously down decreased (<0.01). The renin activity (Ra) and angiotension Ⅱ (Ang Ⅱ) in renal and circulating blood were decreased significantly (<0.01). CONCLUSIONS The effects of 6-week intensive training on renal function in rats and the mechanism of exercise-induced proteinuria may be that overtraining can induce the continuous excitation of Reninrenin activity in renal and circulating blood, down-regulated the expression of Nephrin, lead to abnormality of renal structure and function, and proteinuria.
Animals ; Blood Urea Nitrogen ; Corticosterone ; blood ; Creatinine ; blood ; Kidney ; physiopathology ; Male ; Membrane Proteins ; metabolism ; Physical Conditioning, Animal ; adverse effects ; Proteinuria ; Rats ; Rats, Sprague-Dawley ; Renin-Angiotensin System ; Testosterone ; blood

Objective: To investigate the clinical effects of oral Testosterone Undecanoate Capsules (TUC) combined with Qilin Pills (QLP) on late-onset hypogonadism (LOH) in men. METHODS: Sixty-three LOH patients meeting the inclusion criteria were randomly divided into a control group (aged ［48.4 ± 6.2］ yr, n = 32) and an experimental group (aged ［47.2 ± 5.6］ yr, n = 31) to be treated with oral TUC (80 mg, qd) and TUC + QLP (6g, tid), respectively, both for 3 months. Comparisons were made between the two groups of patients in the IIEF-5 scores, total testosterone (TT) levels, and scores in the Aging Males' Symptoms (AMS) scale before and after treatment. RESULTS: After treatment, the patients of the experimental group, as compared with the controls, showed a significantly increased IIEF-5 score (21.7 ± 5.8 vs 15.9 ± 4.7, P <0.05) and TT level (［16.7 ± 2.2］ vs ［13.1 ± 2.8］ nmol/L, P <0.05), but a decreased AMS score (20.7 ± 5.7 vs 31.3±6.5, P <0.05). CONCLUSIONS TUC combined with Qilin Pills has a better effect and a lower rate of adverse reactions than TUC used alone in the treatment of late-onset hypogonadism in males.
Androgens ; administration & dosage ; adverse effects ; Capsules ; Drug Therapy, Combination ; adverse effects ; Drugs, Chinese Herbal ; administration & dosage ; adverse effects ; Humans ; Hypogonadism ; blood ; drug therapy ; Male ; Middle Aged ; Testosterone ; administration & dosage ; adverse effects ; analogs & derivatives ; blood

Klinefelter's syndrome (KS) is a most frequent sex chromosomal disorder in males, which is characterized by hypogonadism and infertility. The development of assisted reproductive technology has made it possible for KS males to father children. Microdissection testicular sperm extraction (mTESE) is widely considered to be the best method for sperm retrieval in KS patients. This article presents an overview on mTESE for men with non-mosaic KS in the aspects of its predictors, sperm retrieval rate, operation procedure, preoperative hormonal therapy, and postoperative complications and testosterone reduction.
Adult ; Humans ; Klinefelter Syndrome ; genetics ; Male ; Microdissection ; adverse effects ; methods ; Postoperative Complications ; etiology ; Sperm Retrieval ; Spermatozoa ; Testis ; Testosterone

Objective: To investigate the clinical effects of aripiprazole on sexual dysfunction induced by amisulpride or risperidone in male patients with schizophrenia. METHODS: This study included 75 male patients with drug-induced secondary sexual dysfunction after treated with amisulpride or risperidone for first-episode schizophrenia between October 2014 and October 2016. We substituted aripiprazole for amisulpride or risperidone, gradually increased the dose from 10 to 30 mg/d within 2 weeks, and maintained 30 mg/d from the 3rd week. At 4 and 8 weeks after medication, we evaluated the sexual function of the patients, measured the levels of serum prolactin (PRL) and testosterone (T), obtained the scores of the Positive and Negative Symptoms Scale (PANSS), recorded adverse reactions, and compared the parameters with those before aripiprazole administration. RESULTS: Compared with pre-aripiprazole administration, the patients showed significant increases after 4 weeks of medication in the sexual function score (24.3 ± 2.1 vs 32.6 ± 3.6, P <0.05) and T level (［13.3 ± 2.7］ vs ［17.4±3.0］ mmol/L, P <0.05) but a decreased level of PRL (［38.5 ± 10.5］ vs ［27.9 ± 8.2］ ng/ml, P <0.05). At 8 weeks, the sexual function score and serum PRL were both restored to the baseline levels at admission, and the erectile function score, ejaculation score, total score, and serum T level even exceeded the baseline, though with no statistically significant differences (P >0.05). In comparison with pre-aripiprazole administration, the PANSS score was significantly decreased at 4 weeks after medication (62.1 ± 4.9 vs 57.2 ± 5.5, P <0.05) and even lower at 8 weeks (51.2 ± 5.2) (P <0.05). The incidence rates of medication-related excitation, dizziness, insomnia, and loss of appetite were 6.7%, 5.3%, 4.0% and 1.3% respectively, and no other serious adverse reactions were observed. CONCLUSIONS Aripiprazole is effective for the treatment of drug-induced sexual dysfunction in schizophrenic men by continuously alleviating their positive and negative symptoms and meanwhile improving their sexual function and restoring their sexual hormone levels.
Amisulpride ; Antipsychotic Agents ; administration & dosage ; adverse effects ; Aripiprazole ; administration & dosage ; Drug Administration Schedule ; Humans ; Male ; Prolactin ; blood ; Risperidone ; adverse effects ; Schizophrenia ; blood ; drug therapy ; Sexual Behavior ; Sexual Dysfunction, Physiological ; blood ; chemically induced ; drug therapy ; Sulpiride ; adverse effects ; analogs & derivatives ; Testosterone ; blood ; Treatment Outcome