Current National and International Guidelines for the Management of Male Hypogonadism: Helping Clinicians to Navigate Variation in Diagnostic Criteria and Treatment Recommendations

Ahmed Al-Sharefi,Richard Quinton 대한내분비학회 2020 Endocrinology and metabolism Vol.35 No.3

Male hypogonadism—rebadged by some as testosterone deficiency syndrome—is a clinical and biochemical diagnosis of increasingworldwide interest. Organic male hypogonadism—usually permanent—is well-established, but aging men may also exhibit lowerserum testosterone levels; principally due to burden of extra-gonadal comorbidities such as obesity, diabetes and metabolic syndrome, but with an underlying intact hypothalamo-pituitary-testicular (HPT) axis capable of springing back into operation once comorbidities are addressed. Despite encouraging observational data and plausible theoretical underpinning, evidence for efficacy andsafety of testosterone in this “aging” group of men is lacking; addressing comorbid illnesses remains the key priority instead. Nevertheless, in recent years, accumulation of misleading information online has triggered a global tsunami of testosterone prescriptions. Despite this, many men with organic hypogonadism remain undiagnosed or untreated; many more face a diagnostic odyssey beforeachieving care by the appropriate specialist. As testosterone therapy is not without risk several clinical practice guidelines have beenpublished specialist societies to guide physicians on best practice. However, these are heterogeneous in key areas, reflecting divergent approaches to the same evidence basis. Herein, we navigate the major clinical practice guidelines on male hypogonadism andtest their respective recommendations against current best evidence.

갑상샘기능저하증에 따른 생식샘기능저하증 모델 정립을 위한 제언

윤상필,김정우,Yoon, Sang-Pil,Kim, Jung Woo 제주대학교 의과학연구소 2019 The Journal of Medicine and Life Science Vol.16 No.1

Hypogonadism is a clinical syndrome that results in hormone deficiency and can be classified as 1) primary caused by the gonadal failure and 2) secondary by the hypothalamus-pituitary gland dysfunction and/or cardiometabolic complications. Recently the presence of thyroid hormone receptors in different testicular cell types was demonstrated, and thus thyroid dysfunctions would be another cause of secondary hypogonadism. Thus, we investigated the effects of perinatal hypothyroidism on hypogonadism in male Sprague-Dawley rats. Perinatal hypothyroidism was induced by daily administration of 0.05% 6-propyl-2-thiouracil (PTU) by tap water from gestation day 15, which were compared with negative control (PTU (-)) group. At postnatal day 28, hypothyroid pups were divided into 2 groups: PTU (+) group - continued PTU treatment and PTU (+/-) group - stopped PTU until postnatal day 49. Body weights, dehydrotesosterone (DHT), and testosterone levels were checked 2 and 3 weeks after grouping. Body weights were significantly decreased in PTU(+) and PTU(+/-) groups compared with PTU (-) group at postnatal day 28. 3 weeks later, PTU (+/-) group significantly gained weight compared with PTU (+) group. DHT and testosterone levels significantly decreased with PTU treatment, but increased 3 weeks after stopping PTU administration. Perinatal PTU-induced hypothyroid hypogonadism was sustained for 2 weeks after stopping PTU administration, but restored gonadal hormone levels 3 weeks after stopping PTU. These results suggest that researchers should design an experiment on hypothyroid hypogonadism based on the estimated period.

강직척추염과 동반된 일차성 성선기능저하증

전병연,이국진,김지현,이정민,장상아 대한내분비학회 2008 Endocrinology and metabolism Vol.23 No.5

Male patients with hypogonadism have an increased risk of developing rheumatic diseases. Most causes of hypogonadism related with rheumatic disease are karyotype abnormality such as Klinefelter’s syndrome or Turner’s syndrome and gonadal dysgenesis. A 24-year-old year male was admitted for pain of both hip joints that had worsened over 2 months. He had hip joint involvement from ankylosing spondylitis and did not show secondary sex characteristics. His sex hormones and gonadotropins levels indicated hypergonadotropic hypogonadism. The karyotype was 46 XY, and there was no obvious cause of hypogonadism. Here we report on clinical features of this first Korean case of primary hypogonadism accompanying ankylosing spondylitis.

Rapid Differentiation of Human Embryonic Stem Cells into Testosterone-Producing Leydig Cell-Like Cells In vitro

Shin Eun-Young,Park Seah,Choi Won Yun,이동율 한국조직공학과 재생의학회 2021 조직공학과 재생의학 Vol.18 No.4

Background: Leydig cells (LCs) are testicular somatic cells that are the major producers of testosterone in males. Testosterone is essential for male physiology and reproduction. Reduced testosterone levels lead to hypogonadism and are associated with diverse pathologies, such as neuronal dysfunction, cardiovascular disease, and metabolic syndrome. LC transplantation is a promising therapy for hypogonadism; however, the number of LCs in the testis is very rare and they do not proliferate in vitro. Therefore, there is a need for an alternative source of LCs. Methods: To develop a safer, simple, and rapid strategy to generate human LC-like cells (LLCs) from stem cells, we first performed preliminary tests under different conditions for the induction of LLCs from human CD34/CD73 double positive-testis-derived stem cells (HTSCs). Based on the embryological sequence of events, we suggested a 3-step strategy for the differentiation of human ESCs into LLCs. We generated the mesendoderm in the first stage and intermediate mesoderm (IM) in the second stage and optimized the conditions for differentiation of IM into LLCs by comparing the secreted testosterone levels of each group. Results: HTSCs and human embryonic stem cells can be directly differentiated into LLCs by defined molecular compounds within a short period. Human ESC-derived LLCs can secrete testosterone and express steroidogenic markers. Conclusion: We developed a rapid and efficient protocol for the production of LLCs from stem cells using defined molecular compounds. These findings provide a new therapeutic cell source for male hypogonadism. Background: Leydig cells (LCs) are testicular somatic cells that are the major producers of testosterone in males. Testosterone is essential for male physiology and reproduction. Reduced testosterone levels lead to hypogonadism and are associated with diverse pathologies, such as neuronal dysfunction, cardiovascular disease, and metabolic syndrome. LC transplantation is a promising therapy for hypogonadism; however, the number of LCs in the testis is very rare and they do not proliferate in vitro. Therefore, there is a need for an alternative source of LCs. Methods: To develop a safer, simple, and rapid strategy to generate human LC-like cells (LLCs) from stem cells, we first performed preliminary tests under different conditions for the induction of LLCs from human CD34/CD73 double positive-testis-derived stem cells (HTSCs). Based on the embryological sequence of events, we suggested a 3-step strategy for the differentiation of human ESCs into LLCs. We generated the mesendoderm in the first stage and intermediate mesoderm (IM) in the second stage and optimized the conditions for differentiation of IM into LLCs by comparing the secreted testosterone levels of each group. Results: HTSCs and human embryonic stem cells can be directly differentiated into LLCs by defined molecular compounds within a short period. Human ESC-derived LLCs can secrete testosterone and express steroidogenic markers. Conclusion: We developed a rapid and efficient protocol for the production of LLCs from stem cells using defined molecular compounds. These findings provide a new therapeutic cell source for male hypogonadism.

남성갱년기증상과 혈중 총테스토스테론의 일중변동이 소실된 남성에서의 남성호르몬보충요법

김은탁,이종현,정지훈,조현욱,주현택,박진성,우승효,김대경 대한남성과학회 2010 The World Journal of Men's Health Vol.28 No.3

Purpose: It is known that the loss of diurnal rhythm of testosterone by age is related to late-onset hypogonadism (LOH). Currently testosterone replacement therapy (TRT) has been recommended only in men with hypogonadism. We evaluated the effectiveness and safety of TRT for men with LOH symptoms and the loss of diurnal rhythm of total testosterone but normal values of total testosterone. Materials and Methods: We enrolled 62 patients in whom the difference in testosterone between morning and evening was lower than 108 ng/dl, whose morning values were higher than 300 ng/dl, and who were diagnosed with LOH using the Androgen Deficiency in Aging Male (ADAM) questionnaire. Among the 62 patients enrolled, 44 completed the daily application of 1% testosterone gel or the intramuscular injection of long-acting testosterone undecanoate for the full 20-week period. We compared the data at baseline, and the 8th and 20th week using the Aging Males' Symptoms (AMS) scale, the International Index of Erectile Function (IIEF)-15, the International Prostate Symptoms Score (IPSS), and the serum levels of total testosterone, prostate specific antigen (PSA), complete blood cell count (CBC), and lipid profile. Results: The mean age was 54.9±7.2 years. Subjects main symptoms were sexual dysfunction and decrease of ejaculate volume. AMS scales before and after TRT were 41.3±18.5 and 35.8±19.7 (p<0.05). IIEF total scores before and after TRT were 29.7±13.7 and 38.9±17.4 (p<0.001). However, 18 patients (40.9%) were not satisfied with TRT and only 11% were fully satisfied. Total testosterone and estradiol were higher after TRT but the other values had not changed. The most common adverse event (27.3%) was erythrocystosis (18.2%). Conclusions: TRT could induce total testosterone to reach the mid-normal level and was relatively effective for aging male symptoms and sexual function. It is essential for physician to inform patients about potential adverse events and the low satisfaction rate associated with TRT even though TRT has generally been effective.

후천성 남성 저고나도트로핀성 저성선증에서의 임신유도

한거름,이재석,서주태 大韓泌尿器科學會 2003 Korean Journal of Urology Vol.44 No.2

The Relationship between Testosterone Deficiency and Men’s Health

Akira Tsujimura 대한남성과학회 2013 The World Journal of Men's Health Vol.31 No.2

Testosterone is important in the physiology of various organs and tissues. The serum testosterone concentration gradually declines as one of the processes of aging. Thus, the concept of late-onset hypogonadism has gained increasing attention in the last few years. Reported symptoms of late-onset hypogonadism are easily recognized and include diminished sexual desire and erectile quality, particularly in nocturnal erections, changes in mood with concomitant decreases in intellectual activity and spatial orientation, fatigue, depression and anger, a decrease in lean body mass with associated decreases in muscle volume and strength, a decrease in body hair and skin alterations, and decreased bone mineral density resulting in osteoporosis. Among these various symptoms, sexual dysfunction has been the most common and necessary to treat in the field of urology. It is well known that a low serum testosterone level is associated with erectile dysfunction and hypoactive sexual libido and that testosterone replacement treatment can improve these symptoms in patients with hypogonadism. Recently, in addition to sexual dysfunction, a close relationship between metabolic syndrome, characterized by central obesity, insulin resistance, dyslipidemia, and hypertension, and late-onset hypogonadism has been highlighted by several epidemiologic studies. Several randomized control trials have shown that testosterone replacement treatment significantly decreases insulin resistance in addition to its advantage for obesity. Furthermore, metabolic syndrome is one of the major risk factors for cardiovascular disease, and a low serum testosterone level is closely related to the development of atherosclerosis. Presently, it is speculated that a low serum testosterone level may increase the risk for cardiovascular disease. Thus, testosterone is a key molecule in men’s health, especially that of elderly men.

저생식샘자극호르몬 생식샘저하증과 부분 성장호르몬 부분결핍에 동반된 심한 자궁 저형성 1례

민세라,추영광,조현석,이현수,김자경,이향아,안성연 대한소아내분비학회 2012 Annals of Pediatirc Endocrinology & Metabolism Vol.17 No.2

Congenital hypogonadotropic hypogonadism is one of the causes of pubertal failure and primary amenorrhea, it is related to uterine hypotrophy. If the uterus is extremely hypotrophied, it is difficult to identify in imaging studies and can be misdiagnosed as a structural anomaly of internal genitalia. We report a case of extreme uterine hypotrophy in 18-year-old girl with primary amenorrhea that was finally diagnosed as hypogonadotrophic hypogonadism. The patient was initially suspected of Müllerian agenesis owing to the invisible uterus. After 4 months of treatment with estrogen, she showed significant growth of the uterus. 사춘기 지연이 있는 여자 환자에서 영상검사에서 자궁이 관찰되지 않을 때, 자궁의 발육부전인지 뮐러관 무발생인지를감별하는 것은 쉽지 않다. 이러한 경우에는 진단을 하기 전 호르몬 검사, 염색체 검사 등의 결과를 함께 평가하여야 하며, 에스트로겐 투여 후 자궁의 변화를 관찰해보는 것도 방법중의 방법 중의 하나이다. 저자들은 초기에 뮐러관 무발생을 의심하였다가 최종적으로 저생식샘자극호르몬 생식샘저하증으로 진단하고 에스트로겐 투여 후 자기공명영상을 통하여 자궁의 발육을 확인하였던 심한 자궁 저형성 증례를 경험하였기에 보고하는 바이다.

Treatment of congenital hypogonadotropic hypogonadism in male patients

Lee Hae Sang,Shim Young Suk,Hwang Jin Soon 대한소아내분비학회 2022 Annals of Pediatirc Endocrinology & Metabolism Vol.27 No.3

Congenital hypogonadotropic hypogonadism (CHH) is characterized by complete or partial failure of pubertal development because of inadequate secretion of gonadotropic hormones. CHH consists of hypogonadotropic hypogonadism with anosmia or hyposmia, Kallmann syndrome, and the normosmic variation normosmic idiopathic hypogonadotropic hypogonadism. CHH is one of the few treatable diseases of male infertility, although men with primary testicular dysfunction have irreversibly diminished spermatogenic capacity. The approach to CHH treatment is determined by goals such as developing virilization or inducing fertility. This review focuses on the current knowledge of therapeutic modalities for inducing puberty and fertility in men with CHH.

Histomorphological changes in the common carotid artery of the male rat in induced hypogonadism

Isaac Cheruiyot,Beda Olabu,Martin Kamau,Kevin Ongeti,Pamela Mandela 대한해부학회 2018 Anatomy & Cell Biology Vol.51 No.4

The role of androgens in the development of cardiovascular diseases remains controversial. The current study therefore sought to determine the changes in the histomorphology of the common carotid artery of the male rat in orchidectomy-induced hypogonadism. Twenty-two Rattus norvegicus male rats aged 2 months were used. The rats were randomly assigned into baseline (n=4), experimental (n=9), and control (n=9) groups. Hypogonadism was surgically induced in the experimental group by bilateral orchiectomy under local anesthesia. At experiment weeks 3, 6, and 9, three rats from each group (experimental and control) were euthanized, their common carotid artery harvested, and routine processing was done for paraffin embedding, sectioning, and staining. The photomicrographs were taken using a digital photomicroscope for morphometric analysis. Orchidectomy resulted in the development of vascular fibrosis, with a significant increase in collagen fiber density and decrease in smooth muscle and elastic fiber density. Moreover, there was development of intimal hyperplasia, with fragmentation of medial elastic lamellae in the common carotid artery of the castrated rats. Orchidectomy induces adverse changes in structure of the common carotid artery of the male rat. These changes may impair vascular function, therefore constituting a possible structural basis for the higher incidences of cardiovascular diseases observed in hypogonadism.