"Slipped capital femoral epiphysis in a 25-year-old hypogonadic man with a large cranial chondroma: causality or coincidence? ".

BACKGROUND: Slipped capital femoral epiphysis (SCFE) is a hip disorder frequently occurring in adolescence. In adults it is rare and so far very few cases have been documented. CASE PRESENTATION: This report presents a 25-year-old patient diagnosed with an anterior fossa giant chondroma, hypogonadotropic hypogonadism, and SCFE. The patient underwent surgical and hormonal therapy. His symptoms revealed, and he became a father. CONCLUSIONS: Every patient diagnosed with SCFE in adulthood should undergo endocrinological assessment based on physical examination and laboratory tests.

A novel heterozygous mutation of CHD7 gene in a Chinese patient with Kallmann syndrome: a case report.

BACKGROUND: Variants of chromodomain helicase DNA binding protein 7 (CHD7) gene are commonly associated with Kallmann syndrome (KS) and account for 5-6% of idiopathic hypogonadotropic hypogonadism (IHH) cases. Here we report a novel mutation of CHD7 gene in a patient with KS, which may contribute to the better understanding of KS. CASE PRESENTATION: A 29-year-old male patient with KS and a chief complaint of delayed puberty for 13 years (Tanner B Stage< 4) was admitted to the Department of Endocrinology of the First Affiliated Hospital of Zhejiang University (Hangzhou, China) in September 2019. Dual-energy X-ray absorptiometry (DEXA) showed low bone density in both lumbar spine (L1 ~ L5 mean Z-score - 3.0) and femoral neck (Z-score - 2.7). Dynamic contrast-enhanced magnetic resonance imaging (MRI) of pituitary and contrast-enhanced computed tomography (CT) showed no abnormal findings. Ophthalmological evaluation showed that his both eyes showed exotropia, and no sight loss was noted. Heterozygous c.1619G > T mutation of TCD7 gene (p.G4856V) was detected, whereas none of his family members had this mutation. Human chorionic gonadotropin (HCG) and human menopausal gonadotropin (HMG) were injected for three times/week to treat idiopathic hypogonadotropic hypogonadism (IHH). After several months of therapy, the patient's health condition improved. His testicles became larger, and his secondary sexual characteristics improved after treatment. CONCLUSION: Exploration of the novel splice-site mutation of CHD7 may further our current understanding of KS.

Cell adhesion molecule L1 like plays a role in the pathogenesis of idiopathic hypogonadotropic hypogonadism.

PURPOSE: The pathogenesis of idiopathic hypogonadotropic hypogonadism (IHH) is genetically complex. The aims of this study were to investigate the genetic profile and clinical manifestation of IHH in a Chinese pedigree and to discover new IHH-associated genes. METHODS: The first step was to follow up the clinical phenotype and therapeutic outcomes of the pedigree in university hospital. The second step was that mutation screening was performed in this pedigree and 100 healthy controls. The third step was to further verify the pathogenicity of the discovered rare sequencing variant (RSV) by functional experiments. Whole exome sequencing, Sanger sequencing, testicular volume (TV), semen analysis, assessment of cell migration and necroptosis were performed. RESULTS: One heterozygous RSV (p.G517E) in CHL1 was identified in two male IHH patients and their mother in the pedigree, but not in healthy controls. All the three individuals exhibited olfactory impairment. hCG/hMG treatment significantly improved TV, serum testosterone and/or semen parameters of the two male patients. Functional analysis indicated that CHL1 significantly regulated GnRH neuronal cell line (GN11 cells) migration and necroptosis, with alteration of ERK1/2 activation, calcium loading, and transcription of RIPK3 and MLKL. However, the above processes were negatively influenced by the CHL1 RSV. CONCLUSIONS: Our study reports the genetic relevance of CHL1 in IHH, and characterizes the phenotypic and therapeutic profiles in patients carrying the CHL1 RSV. CHL1 may act as a new IHH-associated gene, and should be taken into consideration in future investigations for this field.

Predictors of reproductive and non-reproductive outcomes of gonadotropin mediated pubertal induction in male patients with congenital hypogonadotropic hypogonadism (CHH).

PURPOSE: To investigate predictors of testicular response and non-reproductive outcomes (height, body proportions) after gonadotropin-induced puberty in congenital hypogonadotropic hypogonadism (CHH). DESIGN: A retrospective analysis of the puberty induction in CHH male patients, undergoing an off-label administration of combined gonadotropin (FSH and hCG). METHODS: Clinical and hormonal evaluations before and during gonadotropin stimulation in 19 CHH patients genotyped by Targeted Next Generation Sequencing for CHH genes; 16 patients underwent also semen analysis after gonadotropins. RESULTS: A lesser increase in testicular volume after 24 months of induction was significantly associated with: (I) cryptorchidism; (II) a positive genetic background; (III) a complete form of CHH. We found no significant correlation with the cumulative dose of hCG administered in 24 months. We found no association with the results of semen analyses, probably due to the low numerosity. Measures of body disproportion (eunuchoid habitus and difference between adult and target height: deltaSDSth), were significantly related to the: (I) age at the beginning of puberty induction; (II) duration of growth during the induction; (III) initial bone age. The duration of growth during induction was associated with previous testosterone priming and to partial forms of CHH. CONCLUSIONS: This study shows that a strong genetic background and cryptorchidism, as indicators of a complete GnRH deficiency since intrauterine life, are negative predictors of testicular response to gonadotropin stimulation in CHH. Body disproportion is associated with a delay in treatment and duration of growth during the induction, which is apparently inversely related to previous androgenization.

Hypogonadism in Patients with Prader Willi Syndrome: A Narrative Review.

Prader-Willi syndrome (PWS) is a multisystemic complex genetic disorder related to the lack of a functional paternal copy of chromosome 15q11-q13. Several clinical manifestations are reported, such as short stature, cognitive and behavioral disability, temperature instability, hypotonia, hypersomnia, hyperphagia, and multiple endocrine abnormalities, including growth hormone deficiency and hypogonadism. The hypogonadism in PWS is due to central and peripheral mechanisms involving the hypothalamus-pituitary-gonadal axis. The early diagnosis and management of hypogonadism in PWS are both important for physicians in order to reach a better quality of life for these patients. The aim of this study is to summarize and investigate causes and possible therapies for hypogonadism in PWS. Additional studies are further needed to clarify the role of different genes related to hypogonadism and to establish a common and evidence-based therapy.

Prader-Willi Syndrome and Hypogonadism: A Review Article.

Prader-Labhart-Willi syndrome (PWS) is a rare genetic disorder characterized by intellectual disability, behavioural problems, hypothalamic dysfunction and specific dysmorphisms. Hypothalamic dysfunction causes dysregulation of energy balance and endocrine deficiencies, including hypogonadism. Although hypogonadism is prevalent in males and females with PWS, knowledge about this condition is limited. In this review, we outline the current knowledge on the clinical, biochemical, genetic and histological features of hypogonadism in PWS and its treatment. This was based on current literature and the proceedings and outcomes of the International PWS annual conference held in November 2019. We also present our expert opinion regarding the diagnosis, treatment, care and counselling of children and adults with PWS-associated hypogonadism. Finally, we highlight additional areas of interest related to this topic and make recommendations for future studies.

Testosterone, testosterone therapy and prostate cancer.

With prostate cancer not observed in eunuchs and total androgen suppression by castration an effective first-line treatment for advanced prostate cancer, the dramatic regression seen in tumour symptoms after castration, lead to the theory that high levels of circulating androgens were a risk factor for prostate cancer. This theory however, ignored the effects testosterone variations within a physiologic range could have on early tumour events and since the early 2000s, clinical evidence discounting testosterone as a linear mechanistic cause of prostate cancer growth mounted, with alternative mechanistic hypotheses such as the saturation model being proposed. Together with a growing understanding of the negative health effects and decreased quality of life in men with testosterone deficiency or hypogonadism, a paradigm shift away from testosterone as a prostate cancer inducer occurred allowing clinicians to use testosterone therapy as potential treatment for men with difficult and symptomatic hypogonadism that had been previously treated for prostate cancer. In this review we contextualise the idea of testosterone as a risk factor for prostate cancer inducement and compile the most current literature with regards to the influence of testosterone and testosterone therapy in prostate cancer.

Clinical and genetic analysis in males with 46,XX disorders of sex development: A reproductive centre experience of 144 cases.

To explore the clinical features and assisted reproductive technology (ART) outcomes of 46,XX disorders of sex development (DSD) males, 144 males with 46,XX DSD were recruited in this retrospective study. The baseline information, clinical characteristics and ART outcomes of the participants were collected and analysed. The mean age was 29.06 ± 4.50 years. The mean volumes (95% CI) of left and right testicles were 2.16 (1.82-2.49) ml and 2.16 (1.83-2.49) ml, respectively. Cryptorchidism and/or hypospadias appeared in 19 patients (13.19%). Elevated levels of follicle-stimulating hormone (FSH) were found in 136 patients (95.10%) and increased luteinising hormone (LH) values were detected in 125 patients (92.59%). Eighty subjects (62.99%) had low testosterone values. Among 86 patients with status of sex-determining region Y (SRY)-gene and azoospermia factor (AZF) region available, fifteen (17.44%) patients were SRY-negative and AZF region was absent in every patient without exception. Additionally, fertility achieved in 87 patients through ART using donor spermatozoa. In conclusion, hypergonadotropic hypogonadism appeared as the main presentation of 46,XX DSD males regardless of the SRY status. The available fertility option proved to achieve live birth was limited to ART using donor spermatozoa.

Evaluation and Management of Testosterone Deficiency: AUA Guideline.

PURPOSE: There has been a marked increase in testosterone prescriptions in the past decade resulting in a growing need to give practicing clinicians proper guidance on the evaluation and management of the testosterone deficient patient. MATERIALS AND METHODS: A systematic review utilized research from the Mayo Clinic Evidence Based Practice Center and additional supplementation by the authors. Evidence-based statements were based on body of evidence strength Grade A, B, or C and were designated as Strong, Moderate, and Conditional Recommendations with additional statements presented in the form of Clinical Principles or Expert Opinions (table 1 in supplementary unabridged guideline, http://jurology.com/). RESULTS: This guideline was developed by a multi-disciplinary panel to inform clinicians on the proper assessment of patients with testosterone deficiency and the safe and effective management of men on testosterone therapy. Additional statements were developed to guide the clinician on the appropriate care of patients who are at risk for or have cardiovascular disease or prostate cancer as well as patients who are interested in preserving fertility. CONCLUSIONS: The care of testosterone deficient patients should focus on accurate assessment of total testosterone levels, symptoms, and signs as well as proper on-treatment monitoring to ensure therapeutic testosterone levels are reached and symptoms are ameliorated. Future longitudinal observational studies and clinical trials of significant duration in this space will improve diagnostic techniques and treatment of men with testosterone deficiency as well as provide more data on the adverse events that may be associated with testosterone therapy.

Assisted reproductive techniques with congenital hypogonadotropic hypogonadism patients: a systematic review and meta-analysis.

BACKGROUND: After hormonal replacement therapy (HRT) including androgen replacement or sequential therapy of estrogen and progesterone, The combination of human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG) and pulsatile GnRH, is not sufficient to produce sufficient gametes in some patients with Congenital hypogonadotropic hypogonadism (CHH). A Systematic review and meta-analysis was performed to determine that assisted reproductive techniques (ART) can effectively treat different causes of infertility. METHODS: To determine the effect of ART on fertility of CHH patients and investigate whether outcomes are similar to infertility due to other causes, we conducted a systematic review and meta-analysis of retrospective trials. Clinical trials were systematically searched in Medline, Embase, and the Cochrane central register of controlled trials databases. The keywords and major terms covered "hypogonadotropic hypogonadism", "kallmann syndrome", "assisted reproductive techniques", "intrauterine insemination", "intracytoplasmic sperm injection", "testicular sperm extraction", "in vitro fertilization", "embryo transplantation" and "intra-Fallopian transfer". RESULTS: A total of 388 pregnancies occurred among 709 CHH patients who received ART (effectiveness 46, 95% confidence interval 0.39 to 0.53) in the 20 studies we included. The I2 in trials assessing overall pregnancy rate (PR) per embryo transfer (ET) cycle was 73.06%. Similar results were observed in subgroup analysis by different gender. Regression indicates pregnancy rate decreases with increasing age. Fertilization, implantation and live birth rates (72, 36 and 40%) showed no significant differences as compared to infertility due to other causes. CONCLUSIONS: Despite CHH patients usually being difficult to generate gametes, their actual chances of fertility are similar to subjects with other non-obstructive infertility. ART is a suitable option for CHH patients who do not conceive after long-term gonadotropin treatment.

[Diagnosis and management of adult-onset idiopathic hypogonadotropic hypogonadism].

Objective: To investigate the clinical features and management of male patients with adult-onset idiopathic hypogonadotropic hypogonadism (AIHH). Methods: Clinical features and treatment of six patients with AIHH between January 2010 and June 2017 were retrospectively reviewed. Results: The patients were all male, with an age of 26 (20-35) years old and they experienced complete pubertal development. The main complaints were decreased libido, erectile dysfunction and gynecomastia. Physical examination found that the testicular size was 15 (12-20) ml and they were fully virilized. The serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) and total testosterone was 0.1 (0.1-0.8) U/L, 0.4 (0.1-0.9) U/L and 0.62 (0.10-0.90) nmol/L, respectively. Pituitary MRI and other pituitary hormones were all normal. Testosterone was administrated to three patients and the libido and erectile function returned to normal. Sperm was successfully induced in two patients after combined gonadotropin therapy for 4-6 months. One patient had a reversed hypothalamus-pituitary-testis axis function. Conclusions: The mechanism of male AIHH is unknown. Compared to those with congenital hypogonadotropic hypogonadism, patients with AIHH may achieve better spermatogenesis after gonadotropin therapy. Small portion of patients may have a reversal of hypothalamus-pituitary-testis axis function.

[Diagnosis and treatment of idiopathic hypogonadotropic hypogonadism in males].

Idiopathic hypogonadotropic hypogonadism (IHH) is often caused by hyposecretion of gonadotropin and consequently affects male fertility. The patient with IHH has a smaller penis and testes with spermatogenic dysfunction. At present, IHH is treated mainly with hCG, hMG, GnRH, and their different combinations. However, due to the lack of large-sample evidence, it is not yet clear which therapy is the best option. This article presents an overview of our experience in the treatment of IHH in the last decade and a review of relevant literature, aiming at a deeper insight into this male disease.

Clinical Characteristics, Health Care Utilization and Costs Among Men with Primary or Secondary Hypogonadism in a US Commercially Insured Population.

INTRODUCTION: Hypogonadism is broadly associated with increases in chronic comorbid conditions and health care costs. Little is known about the specific impact of primary and secondary hypogonadism on health care costs. AIM: To characterize the health care cost and utilization burden of primary and secondary hypogonadism in a population of US men with commercial insurance. METHODS: Newly diagnosed patients with International Classification of Diseases, Ninth Revision, Clinical Modification codes associated with specific medical conditions known to have a high prevalence of testosterone deficiency (ie, relating to primary or secondary hypogonadism) or who had fills for testosterone replacement therapy from January 1, 2007 through April 30, 2013 were identified in administrative claims data from the HealthCore Integrated Research Database. A cohort of patients without hypogonadism was matched on demographics and comorbidities. The matched hypogonadism and non-hypogonadism cohorts (n = 5,777 in each cohort) were compared during a 12-month follow-up period. MAIN OUTCOME MEASURES: Direct health care expenditures and utilization were assessed for all causes and for hypogonadism-related claims. Costs included out-of-pocket patient expenditures and those paid by the insurer. RESULTS: Hypogonadism and matched non-hypogonadism cohorts were similar in demographics (mean age = 50 years) and diagnosed comorbid conditions in the 12 months preceding the index date. In the year after the index date, mean all-cause expenditures for patients with hypogonadism increased by 62% (from $5,425 to $8,813) compared with 25% for the matched controls (from $4,786 to $5,992; P < .01 for follow-up difference between groups). Approximately 16% of total mean costs ($1,377), primarily outpatient and pharmacy costs, were identifiable as related to hypogonadism. CONCLUSION: These data from a population of US men with commercial insurance coverage showed a greater resource use burden for patients with primary and secondary hypogonadism compared with similar patients without hypogonadism. Additional management might be required to address unmet need and decrease the cost burden for patients with hypogonadism.

Successful pregnancy and live birth from a hypogonadotropic hypogonadism woman with low serum estradiol concentrations despite numerous oocyte maturations: a case report.

BACKGROUND: The increase in serum estradiol (E2) concentrations during the follicular phase becomes the index of oocyte maturation in vivo. When ovarian stimulation is performed to hypogonadotropic hypogonadism (HH) patients with only follicle stimulating hormone (FSH), proper increase in serum E2 concentrations is not observed. Even if oocytes are obtained, which usually have low fertilization rate. In this report, we would like to present an unique case, in which under low E2 concentrations and without luteinizing hormone (LH) administration, numerous mature oocytes could be obtained and a healthy baby delivered. CASE PRESENTATION: During controlled ovarian stimulation (COS) with only recombinant follicular stimulating hormone (rFSH) administrations, a 26-year-old Japanese woman with hypothalamic amenorrhea (i.e., hypogonadotropic hypogonadism) developed numerous follicles despite low serum E2, 701 pg/ml, and high progesterone (P4) concentrations, 2.11 ng/ml, on the day of induced ovulation. However, 33 cumulus-oocyte complexes (COCs) were successfully obtained; following the embryo culture, four early embryos and six blastocysts were cryopreserved. This patient received hormone replacement therapy (HRT), during which one of six cryopreserved blastocysts was thawed and transferred into the uterine lumen. The patient became pregnant from the first transfer, went through her pregnancy without any complications, and delivered a healthy male baby in the 39th week. Low E2 concentrations in follicular fluids (FFs) are suggestive that aromatase and/or 17ß-hydroxysteroid dehydrogenase (17ß-HSD) could be low. CONCLUSIONS: Serum E2 concentrations may not be the most important index for oocyte maturation during COS, and suggested that oocyte maturation was in progress even under low serum E2 and high P4 conditions. Even if serum E2 concentrations did not properly increase, numerous mature oocytes could be obtained, resulting in the birth of a healthy baby.

Does pituitary suppression affect live birth rate in women with congenital hypogonadotrophic hypogonadism undergoing intra-cytoplasmic sperm injection? A multicenter cohort study.

In this retrospective multicenter cohort study, women with congenital hypogonadotrophic hypogonadism (CHH) (n = 57) who underwent intra-cytoplasmic sperm injection in-between 2010-2014 were compared to age-matched controls with tubal factor infertility (n = 114) to assess ovarian stimulation cycle and pregnancy outcomes. Live birth rates (LBRs) per started cycle were 31.6 and 24.6% in CHH and controls groups, respectively (p = 0.36). Comparable success rates were also confirmed with the logistic regression analysis (OR: 1.44, 95% CI: 0.78-2.67, p = 0.24). Of the 57 women with CHH, 19 were stimulated with the gonadotropin-releasing hormone (GnRH) antagonist protocol, 13 with the long-GnRH-agonist protocol. Pituitary suppression (PS) was not employed in the remaining 25 cases. Compared to women with PS, women without PS had significantly higher embryo implantation rates (21.6 versus 52.6%, p = 0.03). Although there was a trend favoring no PS, LBRs (25.0 versus 40.0%, p = 0.26) per cycle were short of statistical significance. LBRs per cycle (57.1 versus 31.2%, p = 0.11) and miscarriage rates (11.1 versus 16.7%, p = 0.75) were similar between CHH women who were given estrogen + progesterone and progesterone alone to support the luteal phase. In conclusion, the optimal stimulation protocol appears to be exogenous gonadotropin stimulation alone, without PS, and progesterone-only luteal phase support in CHH patients.

Controlled ovarian stimulation and IVF pregnancy in a trisomy X carrier with associated hypogonadotropic hypogonadism.

We describe successful controlled ovarian stimulation (COS) and the first known IVF pregnancy in a trisomy X carrier with associated hypogonadotropic hypogonadism (HH) linked to a chromosome 4 double mutation in the allele of the Gonadotropins Releasing Hormone receptor (GnRHr) gene. Previous administration of low dose of gonadotropins, as recommended in patients with HH, led to poor follicular recruitment. Since trisomy X is a risk factor for diminished ovarian reserve (DOR) and premature ovarian insufficiency (POI), higher doses of gonadotropins led to better ovarian response. The report readknowledges the importance of a correct genetic evaluation in a competent laboratory as a reliable base for treatment planning in this kind of patients.

[Male hypogonadism and its treatment]. / Hypogonadismus u muzu a jeho lécba.

Male hypogonadism can be of various etiology and that reflects its clinical manifestation, diagnostics and treatment. Male hypogonadism leads not only to decreased fertility, but influences the cardiovascular system, mood changes, bone fragility, lipids and other metabolic functions. Diagnosis of hypogonadism can be cumbersome, as well as the choice of optimal hormonal supplementation. The aim of this article is to summarize the basics from symptoms, diagnosis and treatment of male hypogonadism.

Mutations in gonadotropin-releasing hormone signaling pathway in two nIHH patients with successful pregnancy outcomes.

BACKGROUND: Anomalous levels of gonadotropin-releasing hormone (GnRH) secretion result in a variety of reproductive phenotypes associated with infertility or subfertility. The normosmic isolated hypogonadotropic hypogonadism (nIHH) is due to a failure of either GnRH pulsatile secretion in hypothalamus or its reception in pituitary. The spectrum of nIHH-associated alterations continues to expand, especially when additional ethnic populations are investigated. The aim of this study was to uncover genetic causes for nIHH in patients of Russian origin. METHODS: For two nIHH patients referred to infertility clinic, both exons and promoter sequences of 6 GnRH signaling genes were sequenced. RESULTS: Patient 1 was a compound heterozygote for mutations in GnRH and its receptor encoding genes, while in Patient 2 GnRHR mutations were found in homozygous state. In both patients, the coding frame of GnRHR gene harbored missense-mutation Arg139His previously described as founder mutation in Polish and Brazilan patients. IVF/ET treatments were successful, with phenotypically healthy offsprings delivered. CONCLUSION: Polish founder mutation Arg139His in GnRHR was found in two nIHH patients originating from Western region of Russia. Common variant of GnRH-encoding gene, Trp16Ser, could possibly contribute to reproductive phenotypes in patients with heterozygous mutations of other GnRH signaling pathway genes.

[Secondary male hypogonadism induced by sellar space-occupying lesion: Clinical analysis of 22 cases].

OBJECTIVE: To analyze the clinical characteristics of secondary male hypogonadism induced by sellar space-occupying lesion, explore its pathogenesis, and improve its diagnosis and treatment. METHODS: We retrospectively analyzed the clinical data about 22 cases of secondary male hypogonadism induced by sellar space-occupying lesion, reviewed related literature, and investigated the clinical manifestation, etiological factors, and treatment methods of the disease. Hypogonadism developed in 10 of the patients before surgery and radiotherapy (group A) and in the other 12 after it (group B). The patients received endocrine therapy with Andriol (n=7) or hCG (n=15). RESULTS: The average diameter of the sellar space-occupying lesions was significantly longer in group A than in B (ï¼»2.35±0.71ï¼½ vs ï¼»1.83±0.36ï¼½ cm, P<0.05) and the incidence rate of prolactinomas was markedly higher in the former than in the latter group (60% vs 0, P<0.01). The levels of lutein hormone (LH), follicle stimulating hormone (FSH) and testosterone (T) were remarkably decreased in group B after surgery and radiotherapy (P<0.01). Compared with the parameters obtained before endocrine therapy, all the patients showed significant increases after intervention with Andriol or hCG in the T level (ï¼»0.78±0.40ï¼½ vs ï¼»2.71±0.70ï¼½ ng/ml with Andriol; ï¼»0.93±0.44ï¼½ vs ï¼»3.07±0.67ï¼½ ng/ml with hCG) and IIEF-5 score (5.00±2.61 vs 14.50±3.62 with Andriol; 5.36±1.82 vs 15.07±3.27 with hCG) (all P<0.01). The testis volume increased and pubic hair began to grow in those with hypoevolutism. The patients treated with hCG showed a significantly increased testis volume (P<0.01) and sperm was detected in 7 of them, whose baseline testis volume was markedly larger than those that failed to produce sperm (ï¼»11.5±2.3ï¼½ vs ï¼»7.5±2.3ï¼½ ml, P<0.01). Those treated with Andriol exhibited no significant difference in the testis volume before and after intervention and produced no sperm, either. CONCLUSIONS: Hypothyroidism might be attributed to surgery- or radiotherapy-induced damage to the pituitary tissue, space-occupying effect of sellar lesion, and hyperprolactinemia. Both Andriol and hCG can improve the T level and erectile function, but the former does not help spermatogenesis.