Hypogonadotropic hypogonadism (HH) represents a relatively rare cause of nonobstructive azoospermia (NOA), but its knowledge is crucial for the clinical andrologists, as it represents a condition that can be corrected with medical therapy in 3 quarters of cases. There are forms of congenital HH, whether or not associated with an absent sense of smell (anosmic HH or Kallmann syndrome, and normosmic HH, respectively), and forms of acquired HH. In congenital HH, complete absence of pubertal development is characteristic. On the other hand, if the deficit occurs after the time of pubertal development, as in acquired HH patients, infertility and typical symptoms of late-onset hypogonadism are the main reasons for seeking medical assistance. Gonadotropin-releasing hormone (GnRH) or gonadotropin replacement therapy is the mainstay of drug therapy and offers excellent results, although a small but significant proportion of patients do not achieve sufficient responses.
Humans ; Hypogonadism/drug therapy* ; Male ; Azoospermia/drug therapy* ; Gonadotropin-Releasing Hormone/therapeutic use* ; Kallmann Syndrome/drug therapy* ; Hormone Replacement Therapy

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*

This study aimed to ascertain the current status of Japanese sperm banking for young cancer patients. During 2015, we mailed the directors of 695 institutes where sperm cryopreservation might be performed with questionnaires requesting information on the number of patients, age, precryopreservation chemotherapy, semen analyses results and diagnoses, cryopreservation success rate, and causes of unsuccessful cryopreservation. Of these 695 institutes, 92 had cryopreserved sperm before chemotherapy within the study period. In all, 820 cancer patients (237 testicular, 383 hematological, 46 bone and soft tissue, 20 brain, and 134 other malignancy) consulted the responding institutes for sperm cryopreservation. Except for testicular tumor, the number of patients whose sperm was preserved before cancer treatment was low compared to that of young cancer patients. Approximately 20% of patients with malignancies other than testicular tumor underwent chemotherapy before cryopreservation. The success rate of cryopreservation in hematological malignancy was 82.5%, significantly lower than that of both the testicular cancer (93.6%) and other malignancy groups (95.6%) (P < 0.05). The primary reasons for preservation failure were azoospermia and poor semen quality. Patients with hematological malignancies had a higher rate of unsuccessful cryopreservation compared to those in other groups, possibly due to the large number of patients requesting sperm cryopreservation after chemotherapy induction. In Japan, information regarding sperm banking prior to cancer treatment appears to be lacking. Information regarding sperm preservation before chemotherapy should be provided to all Japanese oncologists.
Adolescent ; Adult ; Age Factors ; Azoospermia ; Cryopreservation ; Drug Therapy ; Humans ; Japan/epidemiology* ; Male ; Middle Aged ; Neoplasms/epidemiology* ; Semen Analysis ; Semen Preservation/methods* ; Sperm Banks/statistics & numerical data* ; Surveys and Questionnaires ; Testicular Neoplasms/epidemiology* ; Treatment Outcome ; Young Adult

Objective: To investigate whether the trigger effect of human menopausal gonadotropins (hMG) and human chorionic gonadotropins (hCG) attributes to the treatment of unexplainable non-obstructive azoospermia (NOA). METHODS: We retrospectively analyzed the clinical data about 282 cases of unexplainable NOA treated in the Maternity and Child Health Hospital of Guizhou Province from January 2010 to May 2017. All the patients underwent trigger treatment by intramuscular injection of hMG at 75 IU 3 times a week for 2 weeks, followed by hCG at 2 000 IU twice a week for another 2 weeks, and meanwhile took vitamin E, Levocarnitine and Tamoxifen as an adjunctive therapy. The treatment lasted 3－12 months. RESULTS: Fifty-eight of the 255 patients that completed the treatment were found with sperm in the semen after treatment, all with severe oligoasthenospermia. Forty-seven of the 58 cases received assisted reproductive technology (ART), of which 18 achieved clinical pregnancy. Semen centrifugation revealed no sperm in the other cases, of which 6 were found with epididymal sperm at epididymal and testicular biopsy after treatment and 3 of them achieved clinical pregnancy after ART. Sperm was found in the semen or at epididymal or testicular biopsy in 64 of the patients after treatment, with an effectiveness rate of 25.1%. CONCLUSIONS Trigger treatment by injection of hMG and hCG combined with adjunctive oral medication has a certain effect on unexplainable NOA.
Azoospermia ; drug therapy ; Chorionic Gonadotropin ; therapeutic use ; Drug Administration Schedule ; Epididymis ; Female ; Fertility Agents, Male ; therapeutic use ; Humans ; Injections, Intramuscular ; Male ; Menotropins ; therapeutic use ; Pregnancy ; Pregnancy Rate ; Reproductive Techniques, Assisted ; Retrospective Studies ; Sperm Retrieval ; statistics & numerical data ; Spermatozoa ; Testis

ObjectiveTo observe the clinical effect of Qilin Pills in the treatment of severe oligozoospermia after microsurgical ejaculatory duct reconstruction for obstructive azoospermia.

METHODSWe retrospectively analyzed 75 cases of obstructive azoospermia treated by ejaculatory duct reconstruction followed by administration of Qilin Pills. The patients were divided into a Qilin group (n=42) and a control group (n=33) postoperatively, treated with Qilin Pills and placebo, respectively. After 3 months of medication, we compared the sperm quality between the two groups of patients.

RESULTSAfter 3 months' treatment, all the patients experienced remarkable improvement in sperm quality (P<0.05). Compared with the controls, the patients in the Qilin group showed dramatic increases in sperm concentration, from (0.57±0.25) and (0.60±0.18) ×10⁶/ml before medication to (2.83±0.59) and (1.72 ±0.52) ×10⁶/ml after medication, significantly higher in the Qilin than in the control group (P<0.05). The percentage of grade a sperm was increased from (5.52±5.97) and (5.30±6.26)% to (11.56±9.96) and (10.27±6.52)%, that of grade a+b sperm from (9.68±8.63) and (8.64±10.10)% to (23.42 ±14.10) and (20.81±14.70)%, and that of morphologically normal sperm from (2.00±1.27) and (2.31±0.94)% to (3.54±2.47) and (3.47±1.33)%, respectively. No statistically significant differences were observed in sperm motility and normal sperm morphology between the two groups after treatment (P>0.05). The total effectiveness rate was higher in the Qilin group than in the controls (88.1% vs 72.7%), but with no significant difference between the two groups (P>0.05).

CONCLUSIONSQilin Pills are fairly effective in improving the quantity of sperm in obstructive azoospermia patients after ejaculatory duct reconstruction.

Adult ; Azoospermia ; drug therapy ; surgery ; Drugs, Chinese Herbal ; therapeutic use ; Ejaculatory Ducts ; surgery ; Humans ; Male ; Postoperative Complications ; drug therapy ; Retrospective Studies ; Sperm Count ; Sperm Motility ; Spermatozoa ; drug effects ; physiology

PURPOSE: Androgen replacement therapy has been shown to be safe and effective for most patients with testosterone deficiency. Male partners of infertile couples often report significantly poorer sexual activity and complain androgen deficiency symptoms. We report herein an adverse effect on fertility caused by misusage of androgen replacement therapy in infertile men with hypogonadal symptoms. MATERIALS AND METHODS: The study population consisted of 8 male patients referred from a local clinic for azoospermia or severe oligozoospermia between January 2008 and July 2011. After detailed evaluation at our andrology clinic, all patients were diagnosed with iatrogenic hypogonadism associated with external androgen replacement. We evaluated changes in semen parameters and serum hormone level, and fertility status. RESULTS: All patients had received multiple testosterone undecanoate (NebidoR) injections at local clinic due to androgen deficiency symptoms combined with lower serum testosterone level. The median duration of androgen replacement therapy prior to the development of azoospermia was 8 months (range: 4-12 months). After withdrawal of androgen therapy, sperm concentration and serum follicle-stimulating hormone level returned to normal range at a median 8.5 months (range: 7-10 months). CONCLUSION: Misusage of external androgen replacement therapy in infertile men with poor sexual function can cause temporary spermatogenic dysfunction, thus aggravating infertility.
Adult ; Androgens/administration & dosage/adverse effects/*therapeutic use ; Azoospermia/*drug therapy ; Erectile Dysfunction/drug therapy ; Humans ; Hypogonadism/*drug therapy ; Infertility, Male/*chemically induced/drug therapy ; Male ; Oligospermia/*drug therapy ; Testosterone/administration & dosage/adverse effects/*analogs & derivatives/therapeutic use

PURPOSE: As the survival rate of children with malignancies has increased over past decades, the follow-up in adult long-term survivors of childhood malignancies should focus on late effects of disease and treatment. This study was undertaken to find out whether sexual development was affected by the previous chemotherapy and reproductive function could be evaluated by Tanner stage and serum sex hormone level. METHODS: Pubertal stage and gonadal function were studied in 15 male adults survived 4.3~14.3 years after treatment for acute lymphoblastic leukemia, malignant lymphoma or lymphoma-leukemia during childhood or adolescence. RESULTS: All patients showed more than stage IV sexual maturity rating. Patients treated with cyclophosphamide including maintenance (CY group) had lesser testicular volume (P=.0001). All patients except one who has testicular involvement at diagnosis, showed normal follicle-stimulating hormone, leutenizing hormone, and testosterone level. Semen analysis was done in 2 patients. One patient with Non-CY group showed normal, whereas one with CY group showed azoospermia. It seemed that treatment period (before or during puberty) or prophylactic cranial radiation therapy did not affect sexual development. CONCLUSION: Previous chemotherapy did not affect sexual development. Physical examination, sex hormone level, bone age were not sufficient for detecting reproductive impairment. Semen analysis and GnRH or hCG hormone stimulation test should be done in high risk patients treated with chemotherapeutic agents affecting germ cell function or testicular radiation therapy.
Adolescent ; Adult* ; Azoospermia ; Child ; Cyclophosphamide ; Diagnosis ; Drug Therapy ; Follicle Stimulating Hormone ; Follow-Up Studies ; Germ Cells ; Gonadotropin-Releasing Hormone ; Gonads ; Humans ; Lymphoma* ; Male* ; Physical Examination ; Precursor Cell Lymphoblastic Leukemia-Lymphoma* ; Semen Analysis ; Sexual Development* ; Survival Rate ; Survivors ; Testosterone

Klinefelter's syndrome is characterized by small testes, azoospermia, gynecomastia, and elevated levels of plasma gonadotropins in men with two or more X chromosomes. Previous investigators reported that patients with Klinefelter's syndrome are predisposed to the development of a non-seminomatous germ cell tumor in the mediastinum. It is suggested that this linkage may be due to the hormonal imbalance in Klinefelter's syndrome and consequently, the formation of dysgenetic germ cell and/or abnomal migration of germ cell. We report here a case of Klinefelter's syndrome in a 24-years-old man who was presented with anterior mediastinal mass. The clinical and laborarotory findings were compatible with Klinefelter's syndrome and he was found to have 47 XXY karyotype. Pathological findings for mediastinal mass revealed mixed germ cell tumor composed of mature cystic teratoma and endodermal sinus tumor. He was treated with cis-platin containing chemotherapy and followed up in partial remission.
Azoospermia ; Drug Therapy ; Endodermal Sinus Tumor ; Germ Cells* ; Gonadotropins ; Gynecomastia ; Humans ; Karyotype ; Klinefelter Syndrome* ; Male ; Mediastinum ; Neoplasms, Germ Cell and Embryonal* ; Plasma ; Research Personnel ; Teratoma ; Testis ; X Chromosome

As the number of long-term survivors is increasing with recent advances of anticancer chemotherapeutics, the late toxic effects of anticancer agents are assuming increased importance. Many young men who have been successfully treated with antineoplastic agents develop azoospermia which persist long after cessation of treatment. Post-pubertal sexual development and spermatogenesis are often unaffected in males who have received chemotherapy before puberty. On the basis of this observation and from animal studies it has been suggested that chemotherapy-induced damage to spermatogenesis can be avoided or at least reduced by the induction of a "resting state" of the testes. This can be achieved by analogues of LH-RH or medroxyprogesterone acetate. The aim of present study was to evaluate protective effect from doxorubicin-induced testicular damage with medroxyprogesterone acetate in rats. 1. Comparing with control group, body weight was not changed in medroxyprogesterone acetate treated group. The rats which received doxorubicin displayed significant weight loss. Body weight was decreased more significantly in group III (doxorubicin only administration) than in group IV (medroxyprogesterone acetate and doxorubicin administrational(p <0.001) 2. Testicular weight was markedly decreased by medroxyprogesterone acetate injection but the weight was increased gradually after cessation of administration. In group III and group IV, testicular weights were also decreased markedly, but there was no difference between two groups(p <0.5 ). 3. Sperm head count was reduced with medroxyprogesterone acetate administration but the count was increased gradually after cessation of administration. In group III and group IV sperm head counts were also decreased but more significantly reduced in group III.( <0.005). 4. Repopulation index was diminished with medroxyprogesterone acetate administration up to medical castration level but repopulation index was returned to nearly normal after cessation of administration. In group III and group IV, repopulation indices were also diminished but more significantly diminished in group III.( p <0.005) With above results we can suggest that temporary interruption of the pituitary gonadal axis with medroxyprogesterone acetate may ameliorate the gonadal toxicity of doxorubicin therapy.
Adolescent ; Animals ; Antineoplastic Agents ; Axis, Cervical Vertebra ; Azoospermia ; Body Weight ; Castration ; Doxorubicin* ; Drug Therapy ; Gonadotropin-Releasing Hormone ; Gonads ; Humans ; Male ; Medroxyprogesterone Acetate* ; Medroxyprogesterone* ; Puberty ; Rats* ; Sexual Development ; Sperm Head ; Spermatogenesis ; Survivors ; Testis ; Weight Loss ; Weights and Measures ; Withholding Treatment