When a "Low T" Diagnosis Can Be the Clue to a More Complex Problem.

Male hypogonadism remains a poorly evaluated and managed clinical condition despite the availability of clinical guidelines. We present a case of a male patient diagnosed with secondary hypogonadism related to partial empty sella syndrome, whose clinical course was complicated by a hypotensive near-syncopal event. Although initial hypopituitarism symptoms could be subtle and nonspecific and could involve only one hormonal axis, a thorough evaluation of the pituitary function may identify additional deficiencies such as a subclinical chronic adrenal insufficiency that may become manifest during situations of increased physiological stress with potential life-threatening consequences.

Evaluating the Combination of Human Chorionic Gonadotropin and Clomiphene Citrate in Treatment of Male Hypogonadotropic Hypogonadism: A Prospective Study.

BACKGROUND: In this study, we evaluated MHH patients who wished to preserve fertility, assessing the efficacy of a short course (12 months) of a combined hCG +clomiphene citrate. MATERIALS AND METHODS: The cross-sectional study included 19 patients with hypogonadotropic hypogonadism who were admitted to the Andrology and Fertility Hospital of Hanoi between March 2016 and March 2018. Using hCG every three days in combination with clomiphene citrate 25mg per day until normal testosterone levels are reached, maintain the dose until spermatozoa are present. RESULTS: The mean age was 30.2 ± 5.6. Differences in penis length between the time before and after treatment were significant (p=0.005). The average dose of hCG using in our study was 5579 ± 1773.7 IU. After treatment 6 months and 12 months, the changes in clinical features in all patients and the total hypogonadotropic hypogonadism group were statistically significant (p<0.001). In particular, the differences in testosterone hormone levels in the partial hypogonadotropic hypogonadism group were also statistically significant (p=0.03). No adverse event was observed in our study. The number of patients appearing sperm in the semen is 9 patients (47.4%) after 12 months, but most of the sperm were completely deformed (<1%), and the average motility in the progressive motility group was below 8%. CONCLUSION: In conclusion, a combination of hCG and clomiphene citrate may be an option for MHH patients who desired fertility. After 12 months, 47.4% of patients have sperm in semen but almost all of them were deformity. Hormone profile and secondary sexual characteristics improved significantly. There was no adverse event in our study that considered it as safe therapy.

Gonadotropin Treatment for the Male Hypogonadotropic Hypogonadism.

Hypogonadotropic hypogonadism (HH) is caused by a dysfunction in the hypothalamus and/or the pituitary gland and it can be congenital or acquired. This condition is biochemically characterized by low or inappropriately normal gonadotropin levels along with low total testosterone levels. If fertility is not an issue, testosterone therapy is the treatment of choice to induce and maintain secondary sexual characteristics and sexual function. Spermatogenesis is frequently impaired in patients with HH, but usually responsive to hormonal therapy such as gonadotropin therapy or GnRH supplementary/replacement therapy. When gonadotropins are the choice of treatment, conventional therapy includes human chorionic gonadotropin (hCG) along with different FSH formulations: human menopausal gonadotropins (hMG), highly purified urinary FSH preparations (hpFSH) (e.g., urofollitropin) or recombinant FSH (rFSH). The combination of FSH and hCG demonstrated to be associated with better outcomes than single compounds, whereas similar results were obtained with different FSH preparations in male individuals; both regarding the ability to stimulate spermatogenesis and eventually inducing physiology pregnancy. Gonadotropins can be administered either subcutaneously or intramuscularly. The combination therapy with hCG and FSH for a period of 12-24 months was found to promote testicular growth in almost all patients, spermatogenesis in approximately 80% and pregnancy rates in the range of 50%. Gynecomastia is the most common side effect of gonadotropin therapy and is due to hCG stimulation of aromatase causing increased secretion of estradiol. The therapeutic success is higher in patients with post-pubertal HH, in those without previously undescended testes, in patients with higher baseline testicular volume, who underwent repeated cycles of therapy and in patients with higher baseline inhibin B serum concentrations. Reversal of hypogonadism can occur in up to 10% of patients but its physiopathologic mechanism has yet to be elucidated. In conclusion, gonadotropin therapy is effective in promoting puberty and in supporting spermatogenesis onset and preservation in HH patients with either hypothalamic or pituitary conditions.

Patient-reported outcomes and biochemical alterations during hormonal therapy in men with hypogonadotropic hypogonadism who have finished infertility treatment.

Male hypogonadotropic hypogonadism (MHH) is effectively treated by gonadotropins with a high rate of ejaculate sperm and paternity; however, there is no information regarding the appropriate management, including patient-reported outcomes (PROs), of men with MHH who have finished infertility treatment. To compare health-related quality of life, erectile function and biochemical alterations in men with MHH who were treated with testosterone replacement therapy (TRT) or human chorionic gonadotropin (hCG). Twenty-six MHH patients (mean age: 34 years) who needed to improve their androgen deficiency symptoms underwent either hCG therapy (n = 16, started with self-injection of 2,000-7,500 IU per week) or TRT (n = 10, testosterone enanthate 250 mg every 3 weeks). The 36-item Short Form Health Survey (SF-36) questionnaire, five-item International Index of Erectile Function (IIEF-5) and hormonal and biochemical analyses were assessed every 3 months. Changes and comparison of each treatment regarding these parameters were analyzed. Both hCG and TRT significantly improved all domains of the SF-36, except for bodily pain and social functioning. hCG significantly improved the general and mental health domains compared with TRT. Significant improvements in IIEF-5 were observed with both treatments, showing significant improvement with hCG compared to TRT. TRT caused progressive testicular atrophy. There were significant decreases in waist circumference and triglycerides in both treatment groups and significant elevations in prostate-specific antigen and hematocrit. Both hCG and TRT are effective and safe, with preferable PROs by hCG, for treating androgen deficiency in men with MHH who do not need infertility treatment.

Hypogonadotropic Hypogonadism and Juvenile Idiopathic Arthritis in an African Boy: What is the Pathophysiological Link?

The association between hypogonadotropic hypogonadism and juvenile chronic arthritis has rarely been reported in the literature. We report an untreated case of systemic juvenile idiopathic arthritis in a young African male with co-presentation of hypogonadotropic hypogonadism. Possible pathophysiological and etiological links are discussed. A 16-year-old boy was received in our outpatient department for chronic arthritis with temporomandibular involvement and fever. There was no family history of rheumatic diseases or psoriasis. Body temperature was 39.5°C at admission. The clinical examination found synovitis of wrists and knees and inflammatory lymphadenopathy. This polyarthritis occurred in a context of hypogonadism marked by impuberism of Tanner classification stage P2G2. Laboratory tests showed biological inflammatory syndrome and hyperferritinemia with collapsed glycosylated ferritin at 11%. Hormonal testing found low blood testosterone (0.08 mg/L) and pituitary hormone levels attesting to hypogonadotropic hypogonadism. Screening for infections was negative. The immunological assessment for antinuclear antibodies, rheumatoid factor, and anti-cyclic citrullinated peptide antibodies were negative. Standard radiography showed bilateral wrist carpitis. The olfactory bulb was present and normal by cerebral magnetic resonance imaging. The diagnosis of systemic juvenile idiopathic arthritis associated with hypogonadotropic hypogonadism, probably related to delayed puberty, was retained. A therapy combining corticosteroid, methotrexate for arthritis, and hormone replacement with testosterone led to regression of arthritis, biological inflammatory syndrome, and hypogonadism. The presence of rheumatic disease in this context of hypogonadism, regardless of its cause, is mainly associated with very low testosterone levels and the presentation of arthritis in these patients tends to be more severe.

Evaluation of gonadotropin-replacement therapy in male patients with hypogonadotropic hypogonadism.

Hypogonadotropic hypogonadism (HH) is a rare disease in which medical treatment has a high success rate to achieve fertility. This study aimed to analyze the efficacy of hormone replacement therapy and determine predictive factors for successful spermatogenesis and spontaneous pregnancy in patients with idiopathic HH. A total of 112 patients with low testosterone (T), luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and normal prolactin levels were diagnosed with HH and administered LH and FSH analogs as hormone replacement therapy. During treatment, 96 (85.7%) patients had sperm present in ejaculate samples. Among these patients, 72 were married and wanted a child. Of these 72 patients, 48 (66.7%) of couples had pregnancies from natural conception. After initiation of treatment, the mean time for the appearance of sperm in semen was 9.48 months. There were no significant differences between baseline FSH, T, and LH levels; however, older age, larger testicular size, and low rate of undescended testes were favorable factors for successful spermatogenesis. Larger testicular size and older age were also the main predictive factors for natural conception. We found that patients with undescended testes had a younger age, smaller testes, and lower T levels compared with patients exhibiting descended testes. The rate of sperm found in the ejaculate was not significantly decreased in patients with undescended compared with descended testis (73.7% vs 87.6%, P = 0.261). The medical approach for males with HH and azoospermia provides a successful treatment modality in regard to successful spermatogenesis and achievement of pregnancy.

Evaluation of gonadotropin-replacement therapy in male patients with hypogonadotropic hypogonadism / 亚洲男科学杂志(英文版)

Hypogonadotropic hypogonadism (HH) is a rare disease in which medical treatment has a high success rate to achieve fertility. This study aimed to analyze the efficacy of hormone replacement therapy and determine predictive factors for successful spermatogenesis and spontaneous pregnancy in patients with idiopathic HH. A total of 112 patients with low testosterone (T), luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and normal prolactin levels were diagnosed with HH and administered LH and FSH analogs as hormone replacement therapy. During treatment, 96 (85.7%) patients had sperm present in ejaculate samples. Among these patients, 72 were married and wanted a child. Of these 72 patients, 48 (66.7%) of couples had pregnancies from natural conception. After initiation of treatment, the mean time for the appearance of sperm in semen was 9.48 months. There were no significant differences between baseline FSH, T, and LH levels; however, older age, larger testicular size, and low rate of undescended testes were favorable factors for successful spermatogenesis. Larger testicular size and older age were also the main predictive factors for natural conception. We found that patients with undescended testes had a younger age, smaller testes, and lower T levels compared with patients exhibiting descended testes. The rate of sperm found in the ejaculate was not significantly decreased in patients with undescended compared with descended testis (73.7% vs 87.6%, P = 0.261). The medical approach for males with HH and azoospermia provides a successful treatment modality in regard to successful spermatogenesis and achievement of pregnancy.

Evaluation of gonadotropin-replacement therapy in male patients with hypogonadotropic hypogonadism / 亚洲男科学杂志(英文版)

Hypogonadotropic hypogonadism (HH) is a rare disease in which medical treatment has a high success rate to achieve fertility. This study aimed to analyze the efficacy of hormone replacement therapy and determine predictive factors for successful spermatogenesis and spontaneous pregnancy in patients with idiopathic HH. A total of 112 patients with low testosterone (T), luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and normal prolactin levels were diagnosed with HH and administered LH and FSH analogs as hormone replacement therapy. During treatment, 96 (85.7%) patients had sperm present in ejaculate samples. Among these patients, 72 were married and wanted a child. Of these 72 patients, 48 (66.7%) of couples had pregnancies from natural conception. After initiation of treatment, the mean time for the appearance of sperm in semen was 9.48 months. There were no significant differences between baseline FSH, T, and LH levels; however, older age, larger testicular size, and low rate of undescended testes were favorable factors for successful spermatogenesis. Larger testicular size and older age were also the main predictive factors for natural conception. We found that patients with undescended testes had a younger age, smaller testes, and lower T levels compared with patients exhibiting descended testes. The rate of sperm found in the ejaculate was not significantly decreased in patients with undescended compared with descended testis (73.7% vs 87.6%, P = 0.261). The medical approach for males with HH and azoospermia provides a successful treatment modality in regard to successful spermatogenesis and achievement of pregnancy.

Treatment situation of male hypogonadotropic hypogonadism in pediatrics and proposal of testosterone and gonadotropins replacement therapy protocols.

Male hypogonadotropic hypogonadism (MHH), a disorder associated with infertility, is treated with testosterone replacement therapy (TRT) and/or gonadotropins replacement therapy (GRT) (TRT and GRT, together with HRT hormone replacement therapy). In Japan, guidelines have been set for treatment during adolescence. Due to the risk of rapid maturation of bone age, low doses of testosterone or gonadotropins have been used. However, the optimal timing and methods of therapeutic intervention have not yet been established. The objective of this study was to investigate the current situation of treatment for children with MHH in Japan and to review a primary survey involving councilors of the Japanese Society for Pediatric Endocrinology and a secondary survey obtained from 26 facilities conducting HRT. The subjects were 55 patients with MHH who reached their adult height after HRT. The breakdown of the patients is as follows: 7 patients with Kallmann syndrome, 6 patients with isolated gonadotropin deficiency, 18 patients with acquired hypopituitarism due to intracranial and pituitary tumor, 22 patients with classical idiopathic hypopituitarism due to breech delivery, and 2 patients with CHARGE syndrome. The mean age at the start of HRT was 15.7 yrs and mean height was 157.2 cm. The mean age at reaching adult height was 19.4 yrs, and the mean adult height was 171.0 cm. The starting age of HRT was later than the normal pubertal age and showed a significant negative correlation with pubertal height gain, but it showed no correlation with adult height. As for spermatogenesis, 76% of the above patients treated with hCG-rFSH combined therapy showed positive results, though ranging in levels; impaired spermatogenesis was observed in some with congenital MHH, and favorable spermatogenesis was observed in all with acquired MHH. From the above, we propose the establishment of a treatment protocol for the start low-dose testosterone or low-dose gonadotropins by dividing subjects into two groups to determine different treatment protocols, acquired and congenital MHH, and to conduct them at a timing closer to the onset of puberty, namely, at a timing near entrance to junior high school. We also propose a new HRT protocol using preemptive FSH therapy prior to GRT aimed at achieving future fertility in patients with congenital MHH.

Hormonal therapy (hCG and rhFSH) for infertile men with adult-onset idiopathic hypogonadotropic hypogonadism.

Adult-onset idiopathic male hypogonadotropic hypogonadism (IMHH) is a very rare but treatable disease. This study was conducted to examine the efficacy and safety of a combination of human chorionic gonadotropin (hCG) and recombinant human follicle-stimulating hormone (rhFSH) for inducing spermatogenesis in men with adult-onset IMHH. Seven men (34-45 years of age) with azoospermia and/or sexual dysfunction, with a low serum testosterone concentration, and apulsatile secretion of luteinizing hormone, were referred to our hospital for infertility. All had normal secondary sexual characteristics. Thorough endocrinologic examination and magnetic resonance imaging revealed no identifiable cause of hypogonadotropic hypogonadism. Adult-onset IMHH was diagnosed in all cases and treatment was started with 150 IU rhFSH and 5,000 IU hCG, both administered two times per week. Spermatogenesis was restored in five of the seven patients. During treatment one patient achieved spontaneous pregnancy with his wife, and spermatozoa recovered from the other four patients were frozen for future use in intracytoplasmic sperm injection.

Clinical value of LHRH exciting test in differential diagnosis of constitutional delayed puberty and male hypogonadotropic hypogonadism / 中华内分泌代谢杂志

Objective To analyse the clinical significance of LHRH exciting test in the differential diagnosis of constitutional delayed puberty (CDP) and hypogonadotropic hypogonadism (HH). Methods Eighty-one cases from 1982 to 1998 were investigated and followed up. They were all at genital stage Ⅰ. After injection of 100 ?g LHRH, the blood samples (3 ml) were taken at -15, 0, 15, 30, 45, 60, 90 and 120 min. The serum LH and FSH levels were determined by radioimmunoassay. Then they were followed up every 3-24 months. After they received LHRH exciting test, they were followed up until over 18 years old. According to their puberty development status, they were divided into 3 groups, normal group (n=34),CDP group (n=16) and HH group (n=31),andthemeanage,whenthey received LHRH exciting test, was (10.2?0.9, range 9-14) years, (16.0?1.0, range 14-18) years and (17.1?1.4, range 16-22) years respectively. Results There were no significant differences in serum LH baseline level and peak time in normal, CDP and HH groups, but the serum LH peak level, LH increment (peak LH level minus baseline LH level), LH increment ratio (peak level/baseline level of LH) and the area under LH curve (AUC LH ) of normal group were significantly higher than those of CDP group and HH group (all P