Testosterone Replacement Therapy in Reversing “Andropause”: What Is the Proof-of-Principle?

Lang, Pierre Olivier; Samaras, Dimitris; Samaras, Nikolaos

doi:10.1089/rej.2012.1316

Cited by 16 publications

(11 citation statements)

References 181 publications

(256 reference statements)

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“…TRT can treat symptoms associated with low T. 2,4,5 However, TRT may increase the risk and aggressiveness of prostate cancer, 2,6,7 augment the incidence of adverse cardiovascular events, favor obesity and depression and even increase the rate of mortality in patients. 3,4,8,9 Therefore is not recommended for patients at high risk of such diseases. Moreover, long-term TRT can suppress luteinizing hormone (LH) production, making this approach inappropriate for men who wish to have children.…”

Section: Introductionmentioning

confidence: 99%

Induction of Androgen Formation in the Male by a TAT-VDAC1 Fusion Peptide Blocking 14-3-3ɛ Protein Adaptor and Mitochondrial VDAC1 Interactions

et al. 2014

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Low testosterone (T), a major cause of male hypogonadism and infertility, is linked to mood changes, fatigue, osteoporosis, reduced bone-mass index, and aging. The treatment of choice, T replacement therapy, has been linked with increased risk for prostate cancer and luteinizing hormone (LH) suppression, and shown to lead to infertility, cardiovascular diseases, and obesity. Alternate methods to induce T with lower side effects are desirable. In search of the mechanisms regulating T synthesis in the testes, we identified the 14-3-3ɛ protein adaptor as a negative regulator of steroidogenesis. Steroidogenesis begins in mitochondria. 14-3-3ɛ interacts with the outer mitochondrial membrane voltage-dependent anion channel (VDAC1) protein, forming a scaffold that limits the availability of cholesterol for steroidogenesis. We report the development of a tool able to induce endogenous T formation. Peptides able to penetrate testes conjugated to 14-3-3ɛ site of interaction with VDAC1 blocked 14-3-3ɛ-VDAC1 interactions while at the same time increased VDAC1-translocator protein (18 kDa) interactions that induced steroid formation in rat testes, leading to increased serum T levels. These peptides rescued intratesticular and serum T formation in adult male rats treated with gonadotropin-releasing hormone antagonist, which dampened LH and T production.

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Section: Introductionmentioning

confidence: 99%

Induction of Androgen Formation in the Male by a TAT-VDAC1 Fusion Peptide Blocking 14-3-3ɛ Protein Adaptor and Mitochondrial VDAC1 Interactions

et al. 2014

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“…Hypogonadism, which is common in aging men, may be linked to a number of metabolic and quality-of-life changes, including decreased lean body mass and bone mineral density, increased visceral fat, decreased libido and sexual function, altered mood, and fatigue (Carruthers, 2009; Lang et al, 2012; Morris and Channer, 2012). These changes can be partially overcome by exogenous testosterone administration (Katznelson et al, 1996; Wang et al, 1996; Steidle et al, 2003; Page et al, 2005; Seftel et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Transplantation of alginate-encapsulated seminiferous tubules and interstitial tissue into adult rats: Leydig stem cell differentiation in vivo?

Chen

Jin

Huang

et al. 2016

Molecular and Cellular Endocrinology

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In vivo and in vitro studies were conducted to determine whether testosterone-producing Leydig cells are able to develop from cells associated with rat seminiferous tubules, interstitium, or both. Adult rat seminiferous tubules and interstitium were isolated, encapsulated separately in alginate, and implanted subcutaneously into castrated rats. With implanted tubules, serum testosterone increased through two months. Tubules removed from the implanted rats and incubated with LH produced testosterone, and cells on the tubule surfaces expressed steroidogenic enzymes. With implanted interstitial tissue, serum levels of testosterone remained undetectable. However, co-culture of interstitium plus tubules in vitro resulted in the formation of Leydig cells by both compartments. These results indicate that seminiferous tubules contain both cellular and paracrine factors necessary for the differentiation of Leydig cells, and that the interstitial compartment contains precursor cells capable of forming testosterone-producing Leydig cells but requires stimulation by paracrine factors from the seminiferous tubules to do so.

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“…Male hypogonadism diagnosis requires the presence of both clinical symptoms and low serum T levels [18,21,22]. Wu et al defined hypogonadism as TT serum levels below 11 nmol/l (320 ng/dl), FT below 220 pmol/l (640 pg/dl) and three sexual symptoms [12].…”

Section: Clinical Presentation and Diagnostic Criteriamentioning

confidence: 99%

“…Calculated FT is mostly used to help diagnosis when TT values are between 8 nmol/l (230 ng/dl) and 11 nmol/l (320 ng/dl) [12]. Limit for low FT is under 220 pmol/l [12,22]. Finally, clinical tools for andropause screening have also been developed such as the Saint Louis University Androgen Deficiency in the Aging Male (ADAM) questionnaire (88% sensitivity and 60% specificity) [27] and the Aging Male Symptom (AMS) rating (96% sensitivity and 30% specificity) [28].…”

Section: Clinical Presentation and Diagnostic Criteriamentioning

confidence: 99%

A view of geriatrics through hormones. What is the relation between andropause and well-known geriatric syndromes?

Samaras

Lang

et al. 2013

Maturitas

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a b s t r a c tAge related male hypogonadism, or "andropause", is increasingly recognized as of frequent occurrence in older patients. Diagnosis requires both the presence of clinical symptoms and low testosterone levels. However, diagnosing andropause in this age group may be challenging since symptoms are frequently non specific and testosterone levels are influenced by a multitude of parameters such as lifestyle factors and chronic diseases. In this article we discuss the pathophysiology, definition and diagnostic difficulties of andropause in geriatric patients. Moreover, we review the relation between testosterone levels and frequent geriatric syndromes such as falls, osteoporosis, cognitive and mood disorders, anemia and cardiovascular disease. Finally, we examine the potential benefits and risks of testosterone replacement therapy in this age group.

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Testosterone Replacement Therapy in Reversing “Andropause”: What Is the Proof-of-Principle?

Cited by 16 publications

References 181 publications

Induction of Androgen Formation in the Male by a TAT-VDAC1 Fusion Peptide Blocking 14-3-3ɛ Protein Adaptor and Mitochondrial VDAC1 Interactions

Induction of Androgen Formation in the Male by a TAT-VDAC1 Fusion Peptide Blocking 14-3-3ɛ Protein Adaptor and Mitochondrial VDAC1 Interactions

Transplantation of alginate-encapsulated seminiferous tubules and interstitial tissue into adult rats: Leydig stem cell differentiation in vivo?

A view of geriatrics through hormones. What is the relation between andropause and well-known geriatric syndromes?

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