Androgen Deficiency and Phosphodiesterase Type 5 Expression Changes in Aging Male: Therapeutic Implications

被引:23
作者
Aversa, Antonio [1 ]
Duca, Ylenia [2 ]
Condorelli, Rosita Angela [2 ]
Calogero, Aldo Eugenio [2 ]
La Vignera, Sandro [2 ]
机构
[1] Magna Graecia Univ Catanzaro, Dept Expt & Clin Med, Catanzaro, Italy
[2] Univ Catania, Dept Clin & Expt Med, Catania, Italy
关键词
aging; hypogonadism; erectile dysfunction; sexual desire; pde5; expression; inhibitors; testosterone replacement therapy; elderly; ENDOTHELIAL PROGENITOR CELLS; ARTERIAL ERECTILE DYSFUNCTION; LATE-ONSET HYPOGONADISM; SERUM TESTOSTERONE LEVELS; NITRIC-OXIDE; METABOLIC SYNDROME; LEYDIG-CELLS; CORPUS CAVERNOSUM; OXIDATIVE STRESS; URINARY-BLADDER;
D O I
10.3389/fendo.2019.00225
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The age-related decline of serum T occurs in similar to 20-30% of adult men and it is today defined as late-onset hypogonadism (LOH). In the elderly, such decline becomes more prevalent (up to 60%) and shows-up with erectile dysfunction (ED) and hypoactive sexual desire. A large body of experimental evidences have shown that the combination of T replacement therapy (TRT) and phosphodiesterase type 5 inhibitors (PDE5i) is, usually, effective in restoring erectile function in patients with LOH and ED who have not responded to monotherapy for sexual disturbances. In fact, PDE5is potentiate the action of nitric oxide (NO) produced by endothelial cells, resulting in a vasodilator effect, while T facilitates PDE5i effects by increasing the expression of PDE5 in corpora cavernosa. Meta-analytic data have recognized to PDE5i a protective role on the cardiovascular health in patients with decreased left ventricular ejection fraction. In addition, several studies have shown pleiotropic beneficial effects of these drugs throughout the body (i.e., on bones, urogenital tract and cerebral, metabolic, and cardiovascular levels). TRT itself is able to decrease endothelial dysfunction, oxidative stress and inflammation, thus lowering the cardiovascular risk. Furthermore, untreated hypogonadism could be the cause of PDE5i ineffectiveness especially in the elderly. For these reasons, aging men complaining ED who have LOH should undergo TRT before or at the moment when PDE5i treatment is started.
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页数:11
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共 107 条
[1]   TESTOSTERONE CONCENTRATIONS IN WOMEN AND MEN WITH NIDDM [J].
ANDERSSON, B ;
VERMEULEN, A ;
MARIN, P ;
BJORNTORP, P ;
LISSNER, L .
DIABETES CARE, 1994, 17 (05) :405-411
[2]   PDE5 inhibitors - pharmacology and clinical applications 20 years after sildenafil discovery [J].
Andersson, K-E .
BRITISH JOURNAL OF PHARMACOLOGY, 2018, 175 (13) :2554-2565
[3]   Urinary bladder contraction and relaxation: Physiology and pathophysiology [J].
Andersson, KE ;
Arner, A .
PHYSIOLOGICAL REVIEWS, 2004, 84 (03) :935-986
[4]   Protein kinase G-mediated stimulation of basal Leydig cell steroidogenesis [J].
Andric, Silvana A. ;
Janjic, Marija M. ;
Stojkov, Natasa J. ;
Kostic, Tatjana S. .
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2007, 293 (05) :E1399-E1408
[5]   Tadalafil modulates aromatase activity and androgen receptor expression in a human osteoblastic cell in vitro model [J].
Aversa, A. ;
Fittipaldi, S. ;
Bimonte, V. M. ;
Wannenes, F. ;
Papa, V. ;
Francomano, D. ;
Greco, E. A. ;
Lenzi, A. ;
Migliaccio, S. .
JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION, 2016, 39 (02) :199-205
[6]   Androgens improve cavernous vasodilation and response to sildenafil in patients with erectile dysfunction [J].
Aversa, A ;
Isidori, AM ;
Spera, G ;
Lenzi, A ;
Fabbri, A .
CLINICAL ENDOCRINOLOGY, 2003, 58 (05) :632-638
[7]   Penile pharmacotesting in diagnosing male erectile dysfunction: evidence for lack of accuracy and specificity [J].
Aversa, A ;
Isidori, AM ;
Caprio, M ;
Cerilli, M ;
Frajese, V ;
Fabbri, A .
INTERNATIONAL JOURNAL OF ANDROLOGY, 2002, 25 (01) :6-10
[8]   Is testosterone treatment dangerous for the cardiovascular system in older hypogonadal men? [J].
Aversa, Antonio ;
Francomano, Davide ;
Lenzi, Andrea .
IJC METABOLIC & ENDOCRINE, 2014, 4 :1-3
[9]   Does testosterone supplementation increase PDE5-inhibitor responses in difficult-to-treat erectile dysfunction patients? [J].
Aversa, Antonio ;
Francomano, Davide ;
Lenzi, Andrea .
EXPERT OPINION ON PHARMACOTHERAPY, 2015, 16 (05) :625-628
[10]   Exposure to Phosphodiesterase Type 5 Inhibitors Stimulates Aromatase Expression in Human Adipocytes in vitro [J].
Aversa, Antonio ;
Caprio, Massimiliano ;
Antelmi, Antonella ;
Armani, Andrea ;
Brama, Marina ;
Greco, Emanuela A. ;
Francomano, Davide ;
Calanchini, Matilde ;
Spera, Giovanni ;
Di Luigi, Luigi ;
Rosano, Giuseppe M. C. ;
Lenzi, Andrea ;
Migliaccio, Silvia ;
Fabbri, Andrea .
JOURNAL OF SEXUAL MEDICINE, 2011, 8 (03) :696-704