减重手术治疗肥胖相关男性性腺功能减退症研究进展及机制探讨
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摘要
<正>近年来,肥胖已成为全球普遍关注的公共健康问题,是多种慢性代谢性疾病的高危因素,如2型糖尿病、高血压、心血管疾病、血脂异常、睡眠呼吸暂停综合征、骨质疏松症以及恶性肿瘤等。有大量研究发现男性肥胖患者常存在性腺功能减退,表现为雄激素水平低下而雌激素水平升高,可伴有性功能低下,出现勃起功能障碍(erectile dysfunction,
引文
[1]Martini AC,Molina RI,Tissera A,et al.The impact of obesity on male reproduction:its biological significance[J].Expert Rev Endocrinol Metab,2013,8(2):139-148.
[2]Rosenblatt A,Faintuch J,Cecconello I.Abnormalities of reproductive runction in male obesity before and after bariatric surgery-a comprehensive review[J].Obes Surg,2015,25(7):1281-1292.
[3]Dhindsa S,Miller MG,McWhirter CL,et al.Testosterone concentrations in diabetic and nondiabetic obese men[J].Diabetes care,2010,33(6):1186-1192.
[4]Tajar A,Forti G,O’Neill TW,et al.Characteristics of secondary,primary,and compensated hypogonadism in aging men[J].J Clin Endocrinol Metab,2010,95(4):1810-1818.
[5]Saboor Aftab SA,Kumar S,Barber TM.The role of obesity and type 2 diabetes mellitus in the development of male obesity-associated secondary hypogonadism[J].Clin Endocrinol(Oxf),2013,78(3):330-337.
[6]Sarwer DB,Spitzer JC,Wadden TA,et al.Sexual functioning and sex hormones in men who underwent bariatric surgery[J].Surg Obes Relat Dis,2015,11(3):643-651.
[7]Verderame M,Migliaccio V,Scudiero R.Role of estrogen receptors,P450 aromatase,PCNA and p53 in high-fatinduced impairment of spermatogenesis in rats[J].C R Biol,2018,341(7-8):371-379.
[8]Hammoud AO,Carrell DT,Gibson M,et al.Updates on the relation of weight excess and reproductive function in men:sleep apnea as a new area of interest[J].Asi an JAndrol,2012,14(1):77-81.
[9]Dimitriadis GK,Barber TM.Obesity-related metabolic and reproductive dysfunction:variations between the sexes[J].Expert Rev Endocrinol Metab,2016,11(5):387-393.
[10]Di Vincenzo A,Busetto L,Vettor R,et al.Obesity,male reproductive function and bariatric surgery[J].Front Endocrinol(Lausanne),2018,9:769.
[11]Bachir BG,Jarvi K.Infectious,inflammatory,and immunologic conditions resulting in male infertility[J].Urol Clin North Am,2014,41(1):67-81.
[12]Tunc O,Bakos HW,Tremellen K.Impact of body mass index on seminal oxidative stress[J].Andrologia,2011,43(2):121-128.
[13]Andersen JM,Herning H,Aschim EL,et al.Body mass index is associated with impaired semen characteristics and reduced levels of anti-Müllerian hormone across a wide weight rang[J].PloS One,2015,10(6):e0130210.
[14]Abiad F,Awwad J,Abbas HA,et al.Management of weight loss in obesity-associated male infertility:a spotlight on bariatric surgery[J].Hum Fertil(Camb),2017,20(4):227-235.
[15]Michalakis K,Mintziori G,Kaprara A,et al.The complex interaction between obesity,metabolic syndrome and reproductive axis:a narrative review[J].Metabolism,2013,62(4):457-478.
[16]Grossmann M.Hypogonadism and male obesity:focus on unresolved questions[J].Clin Endocrinol(Oxf),2018,89(1):11-21.
[17]De Lorenzo A,Noce A,Moriconi E,et al.MOSH syndrome(male obesity secondary hypogonadism):clinical assessment and possible therapeutic approaches[J].Nutrients,2018,10(4):474.
[18]Ng Tang Fui M,Prendergast LA,Dupuis P,et al.Effects of testosterone treatment on body fat and lean mass in obese men on a hypocaloric diet[J].BMC Med,2016,14(1):153.
[19]Ng Tang Fui M,Hoermann R,Zajac JD,et al.The effects of testosterone on body composition in obese men are not sustained after cessation of testosterone treatment[J].Clin Endocrinol(Oxf),2017,87(4):336-343.
[20]Corona G,Bianchini S,Sforza A,et al.Hypogonadism as a possible link between metabolic diseases and erectile dysfunction in aging men[J].Hormones(Athens),2015,14(4):569-578.
[21]Soares AH,Horie NC,Chiang LAP,et al.Effects of clomiphene citrate on male obesity-associated hypogonadism:a randomized,double-blind,placebo-controlled study[J].Int J Obes(Lond),2018,42(5):953-963.
[22]Roth MY,Amory JK,Page ST.Treatment of male infertility secondary to morbid obesity[J].Nat Clin Pract Endocrinol Metab,2008,4(7):415-419.
[23]Practice Committee of the American Society for Reproductive Medicine.Diagnostic evaluation of the infertile male:a committee opinion[J].Fertil Steril,2015,103(3):e18-e25.
[24]Xu X,Sun M,Ye J,et al.The effect of aromatase on the reproductive function of obese males[J].Horm Metab Res,2017,49(8):572-579.
[25]Zhao D,Pan L,Zhang F,et al.Successful use of aromatase inhibitor letrozole in NOA with an elevated FSHlevel[J].Andrologia,2014,46(4):456-457.
[26]George JT,Veldhuis JD,Tena-Sempere M,et al.Exploring the pathophysiology of hypogonadism in men with type 2 diabetes:kisspeptin-10 stimulates serum testosterone and LH secretion in men with type 2 diabetes and mild biochemical hypogonadism[J].Clin Endocrinol(Oxf),2013,79(1):100-104.
[27]Escobar-Morreale HF,Santacruz E,Luque-Ramírez M,et al.Prevalence of‘obesity-associated gonadal dysfunction’in severely obese men and women and its resolution after bariatric surgery:a systematic review and metaanalysis[J].Hum Reprod Update,2017,23(4):1-19.
[28]Calderón B,Galdón A,Cala?as A,et al.Effects of bariatric surgery on male obesity-associated secondary hypogonadism:comparison of laparoscopic gastric bypass with restrictive procedures[J].Obes Surg,2014,24(10):1686-1692.
[29]Corona G,Rastrelli G,Monami M,et al.Body weight loss reverts obesity-associated hypogonadotropic hypogonadism:a systematic review and meta-analysis[J].Eur JEndocrinol,2013,168(6):829-843.
[30]Samavat J,Facchiano E,Lucchese M,et al.Hypogonadism as an additional indication for bariatric surgery in male morbid obesity?[J].Eur J Endocrinol,2014,171(5):555-560.
[31]Glina FPA,de Freitas Barboza JW,Nunes VM,et al.What is the impact of bariatric surgery on erectile function?[J].Sex Med Rev,2017,5(3):393-402.
[32]Mora M,Aranda G B,de Hollanda A,et al.Weight loss is a major contributor to improved sexual function after bariatric surgery[J].Surg Endosc,2013,27(9):3197-3204.
[33]Kun L,Pin Z,Jianzhong D,et al.Significant improvement of erectile function after Roux-en-Y gastric bypass surgery in obese Chinese men with erectile dysfunction[J].Obes Surg,2015,25(5):838-844.
[34]El Bardisi H,Majzoub A,Arafa M,et al.Effect of bariatric surgery on semen parameters and sex hormone concentrations[J].Reprod Biomed Online,2016,33(5):606-611.
[35]Samavat J,Cantini G,Lotti F,et al.Massive weight loss obtained by bariatric surgery affects semen quality in morbid male obesity[J].Obes Surg,2018,28(1):69-76.
[36]Reis LO,Zani EL,Saad RD,et al.Bariatric surgery does not interfere with sperm quality-a preliminary long-term study[J].Reprod Sci,2012,19(10):1057-1062.
[37]Lazaros L,Hatzi E,Markoula S,et al.Dramatic reduction in sperm parameters following bariatric surgery:report of two cases[J].Andrologia,2012,44(6):428-432.
[38]Sermondade N,Massin N,Boitrelle F,et al.Sperm parameters and male fertility after bariatric surgery:three case series[J].Reprod Biomed Online,2012,24(2):206-210.
[39]Malin SK,Kashyap SR.Differences in weight loss and gut hormones:Rouen-Y gastric bypass and sleeve gastrectomy surgery[J].Curr Obes Rep,2015,4(2):279-286.
[40]Heppner KM,Baquero AF,Bennett CM,et al.GLP-1Rsignaling directly activates arcuate nucleus kisspeptin action in brain slices but does not rescue luteinizing hormone inhibition in ovariectomized mice during negative energy balance[EB/J].eNeuro,2017.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5247618/pdf/ENEURO.0198-16.2016.pdf.
[41]Plum L,Ahmed L,Febres G,et al.Comparison of glucostatic parameters after hypocaloric diet or bariatric surgery and equivalent weight loss[J].Obesity(Silver Spring),2011,19(11):2149-2157.
[42]Mesarwi O,Polak J,Jun J,et al.Sleep disorders and the development of insulin resistance and obesity[J].Endocrinol Metab Clin North Am,2013,42(3):617-634.
[43]Tena-Sempere M,Barreiro ML.Leptin in male reproduction:the testis paradigm[J].Mol Cell Endocrinol,2002,188(1-2):9-13.
[44]Kalinowski P,Paluszkiewicz R,Wróblewski T,et al.Ghrelin,leptin,and glycemic control after sleeve gastrectomy versus Roux-en-Y gastric bypass-results of a randomized clinical trial[J].Surg Obes Relat Dis,2017,13(2):181-188.
[45]Liu F,Tu Y,Zhang P,et al.Decreased visceral fat area correlates with improved total testosterone levels after Roux-en-Y gastric bypass in obese Chinese males with type 2 diabetes:a 12-month follow-up[J].Surg Obes Relat Dis,2018,14(4):462-468.
[46]Bekaert M,Van Nieuwenhove Y,Calders P,et al.Determinants of testosterone levels in human male obesity[J].Endocrine,2015,50(1):202-211.
[47]Grossmann M.Low testosterone in men with type 2 diabetes:significance and treatment[J].J Clin Endocrinol Metab,2011,96(8):2341-2353.
[48]Rao PM,Kelly DM,Jones TH.Testosterone and insulin resistance in the metabolic syndrome and T2DM in men[J].Nat Rev Endocrinol,2013,9(8):479.
[49]Pitteloud N,Hardin M,Dwyer AA,et al.Increasing insulin resistance is associated with a decrease in Leydig cell testosterone secretion in men[J].J Clin Endocrinol Metab,2005,90(5):2636-2641.
[50]Calderón B,Gómez-Martín JM,Vega-Piíero B,et al.Prevalence of male secondary hypogonadism in moderate to severe obesity and its relationship with insulin resistance and excess body weight[J].Andrology,2016,4(1):62-67.
[51]Trachta P,DostálováI,HaluzíkováD,et al.Laparoscopic sleeve gastrectomy ameliorates m RNA expression of inflammation-related genes in subcutaneous adipose tissue but not in peripheral monocytes of obese patients[J].Mol Cell Endocrinol,2014,383(1-2):96-102.
[52]Fariello RM,Pariz JR,Spaine DM,et al.Association between obesity and alteration of sperm DNA integrity and mitochondrial activity[J].BJU Int,2012,110(6):863-867.
[53]Mah PM,Wittert GA.Obesity and testicular function[J].Mol Cell Endocrinol,2010,316(2):180-186.
[54]Duits FH,van Wely M,van der Veen F,et al.Healthy overweight male partners of subfertile couples should not worry about their semen quality[J].Fertil Steril,2010,94(4):1356-1359.
[55]Kratzsch J,Paasch U,Grunewald S,et al.Resistin correlates with elastase and interleukin-6 in human seminal plasma[J].Reprod Biomed Online,2008,16(2):283-288.
[2]Rosenblatt A,Faintuch J,Cecconello I.Abnormalities of reproductive runction in male obesity before and after bariatric surgery-a comprehensive review[J].Obes Surg,2015,25(7):1281-1292.
[3]Dhindsa S,Miller MG,McWhirter CL,et al.Testosterone concentrations in diabetic and nondiabetic obese men[J].Diabetes care,2010,33(6):1186-1192.
[4]Tajar A,Forti G,O’Neill TW,et al.Characteristics of secondary,primary,and compensated hypogonadism in aging men[J].J Clin Endocrinol Metab,2010,95(4):1810-1818.
[5]Saboor Aftab SA,Kumar S,Barber TM.The role of obesity and type 2 diabetes mellitus in the development of male obesity-associated secondary hypogonadism[J].Clin Endocrinol(Oxf),2013,78(3):330-337.
[6]Sarwer DB,Spitzer JC,Wadden TA,et al.Sexual functioning and sex hormones in men who underwent bariatric surgery[J].Surg Obes Relat Dis,2015,11(3):643-651.
[7]Verderame M,Migliaccio V,Scudiero R.Role of estrogen receptors,P450 aromatase,PCNA and p53 in high-fatinduced impairment of spermatogenesis in rats[J].C R Biol,2018,341(7-8):371-379.
[8]Hammoud AO,Carrell DT,Gibson M,et al.Updates on the relation of weight excess and reproductive function in men:sleep apnea as a new area of interest[J].Asi an JAndrol,2012,14(1):77-81.
[9]Dimitriadis GK,Barber TM.Obesity-related metabolic and reproductive dysfunction:variations between the sexes[J].Expert Rev Endocrinol Metab,2016,11(5):387-393.
[10]Di Vincenzo A,Busetto L,Vettor R,et al.Obesity,male reproductive function and bariatric surgery[J].Front Endocrinol(Lausanne),2018,9:769.
[11]Bachir BG,Jarvi K.Infectious,inflammatory,and immunologic conditions resulting in male infertility[J].Urol Clin North Am,2014,41(1):67-81.
[12]Tunc O,Bakos HW,Tremellen K.Impact of body mass index on seminal oxidative stress[J].Andrologia,2011,43(2):121-128.
[13]Andersen JM,Herning H,Aschim EL,et al.Body mass index is associated with impaired semen characteristics and reduced levels of anti-Müllerian hormone across a wide weight rang[J].PloS One,2015,10(6):e0130210.
[14]Abiad F,Awwad J,Abbas HA,et al.Management of weight loss in obesity-associated male infertility:a spotlight on bariatric surgery[J].Hum Fertil(Camb),2017,20(4):227-235.
[15]Michalakis K,Mintziori G,Kaprara A,et al.The complex interaction between obesity,metabolic syndrome and reproductive axis:a narrative review[J].Metabolism,2013,62(4):457-478.
[16]Grossmann M.Hypogonadism and male obesity:focus on unresolved questions[J].Clin Endocrinol(Oxf),2018,89(1):11-21.
[17]De Lorenzo A,Noce A,Moriconi E,et al.MOSH syndrome(male obesity secondary hypogonadism):clinical assessment and possible therapeutic approaches[J].Nutrients,2018,10(4):474.
[18]Ng Tang Fui M,Prendergast LA,Dupuis P,et al.Effects of testosterone treatment on body fat and lean mass in obese men on a hypocaloric diet[J].BMC Med,2016,14(1):153.
[19]Ng Tang Fui M,Hoermann R,Zajac JD,et al.The effects of testosterone on body composition in obese men are not sustained after cessation of testosterone treatment[J].Clin Endocrinol(Oxf),2017,87(4):336-343.
[20]Corona G,Bianchini S,Sforza A,et al.Hypogonadism as a possible link between metabolic diseases and erectile dysfunction in aging men[J].Hormones(Athens),2015,14(4):569-578.
[21]Soares AH,Horie NC,Chiang LAP,et al.Effects of clomiphene citrate on male obesity-associated hypogonadism:a randomized,double-blind,placebo-controlled study[J].Int J Obes(Lond),2018,42(5):953-963.
[22]Roth MY,Amory JK,Page ST.Treatment of male infertility secondary to morbid obesity[J].Nat Clin Pract Endocrinol Metab,2008,4(7):415-419.
[23]Practice Committee of the American Society for Reproductive Medicine.Diagnostic evaluation of the infertile male:a committee opinion[J].Fertil Steril,2015,103(3):e18-e25.
[24]Xu X,Sun M,Ye J,et al.The effect of aromatase on the reproductive function of obese males[J].Horm Metab Res,2017,49(8):572-579.
[25]Zhao D,Pan L,Zhang F,et al.Successful use of aromatase inhibitor letrozole in NOA with an elevated FSHlevel[J].Andrologia,2014,46(4):456-457.
[26]George JT,Veldhuis JD,Tena-Sempere M,et al.Exploring the pathophysiology of hypogonadism in men with type 2 diabetes:kisspeptin-10 stimulates serum testosterone and LH secretion in men with type 2 diabetes and mild biochemical hypogonadism[J].Clin Endocrinol(Oxf),2013,79(1):100-104.
[27]Escobar-Morreale HF,Santacruz E,Luque-Ramírez M,et al.Prevalence of‘obesity-associated gonadal dysfunction’in severely obese men and women and its resolution after bariatric surgery:a systematic review and metaanalysis[J].Hum Reprod Update,2017,23(4):1-19.
[28]Calderón B,Galdón A,Cala?as A,et al.Effects of bariatric surgery on male obesity-associated secondary hypogonadism:comparison of laparoscopic gastric bypass with restrictive procedures[J].Obes Surg,2014,24(10):1686-1692.
[29]Corona G,Rastrelli G,Monami M,et al.Body weight loss reverts obesity-associated hypogonadotropic hypogonadism:a systematic review and meta-analysis[J].Eur JEndocrinol,2013,168(6):829-843.
[30]Samavat J,Facchiano E,Lucchese M,et al.Hypogonadism as an additional indication for bariatric surgery in male morbid obesity?[J].Eur J Endocrinol,2014,171(5):555-560.
[31]Glina FPA,de Freitas Barboza JW,Nunes VM,et al.What is the impact of bariatric surgery on erectile function?[J].Sex Med Rev,2017,5(3):393-402.
[32]Mora M,Aranda G B,de Hollanda A,et al.Weight loss is a major contributor to improved sexual function after bariatric surgery[J].Surg Endosc,2013,27(9):3197-3204.
[33]Kun L,Pin Z,Jianzhong D,et al.Significant improvement of erectile function after Roux-en-Y gastric bypass surgery in obese Chinese men with erectile dysfunction[J].Obes Surg,2015,25(5):838-844.
[34]El Bardisi H,Majzoub A,Arafa M,et al.Effect of bariatric surgery on semen parameters and sex hormone concentrations[J].Reprod Biomed Online,2016,33(5):606-611.
[35]Samavat J,Cantini G,Lotti F,et al.Massive weight loss obtained by bariatric surgery affects semen quality in morbid male obesity[J].Obes Surg,2018,28(1):69-76.
[36]Reis LO,Zani EL,Saad RD,et al.Bariatric surgery does not interfere with sperm quality-a preliminary long-term study[J].Reprod Sci,2012,19(10):1057-1062.
[37]Lazaros L,Hatzi E,Markoula S,et al.Dramatic reduction in sperm parameters following bariatric surgery:report of two cases[J].Andrologia,2012,44(6):428-432.
[38]Sermondade N,Massin N,Boitrelle F,et al.Sperm parameters and male fertility after bariatric surgery:three case series[J].Reprod Biomed Online,2012,24(2):206-210.
[39]Malin SK,Kashyap SR.Differences in weight loss and gut hormones:Rouen-Y gastric bypass and sleeve gastrectomy surgery[J].Curr Obes Rep,2015,4(2):279-286.
[40]Heppner KM,Baquero AF,Bennett CM,et al.GLP-1Rsignaling directly activates arcuate nucleus kisspeptin action in brain slices but does not rescue luteinizing hormone inhibition in ovariectomized mice during negative energy balance[EB/J].eNeuro,2017.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5247618/pdf/ENEURO.0198-16.2016.pdf.
[41]Plum L,Ahmed L,Febres G,et al.Comparison of glucostatic parameters after hypocaloric diet or bariatric surgery and equivalent weight loss[J].Obesity(Silver Spring),2011,19(11):2149-2157.
[42]Mesarwi O,Polak J,Jun J,et al.Sleep disorders and the development of insulin resistance and obesity[J].Endocrinol Metab Clin North Am,2013,42(3):617-634.
[43]Tena-Sempere M,Barreiro ML.Leptin in male reproduction:the testis paradigm[J].Mol Cell Endocrinol,2002,188(1-2):9-13.
[44]Kalinowski P,Paluszkiewicz R,Wróblewski T,et al.Ghrelin,leptin,and glycemic control after sleeve gastrectomy versus Roux-en-Y gastric bypass-results of a randomized clinical trial[J].Surg Obes Relat Dis,2017,13(2):181-188.
[45]Liu F,Tu Y,Zhang P,et al.Decreased visceral fat area correlates with improved total testosterone levels after Roux-en-Y gastric bypass in obese Chinese males with type 2 diabetes:a 12-month follow-up[J].Surg Obes Relat Dis,2018,14(4):462-468.
[46]Bekaert M,Van Nieuwenhove Y,Calders P,et al.Determinants of testosterone levels in human male obesity[J].Endocrine,2015,50(1):202-211.
[47]Grossmann M.Low testosterone in men with type 2 diabetes:significance and treatment[J].J Clin Endocrinol Metab,2011,96(8):2341-2353.
[48]Rao PM,Kelly DM,Jones TH.Testosterone and insulin resistance in the metabolic syndrome and T2DM in men[J].Nat Rev Endocrinol,2013,9(8):479.
[49]Pitteloud N,Hardin M,Dwyer AA,et al.Increasing insulin resistance is associated with a decrease in Leydig cell testosterone secretion in men[J].J Clin Endocrinol Metab,2005,90(5):2636-2641.
[50]Calderón B,Gómez-Martín JM,Vega-Piíero B,et al.Prevalence of male secondary hypogonadism in moderate to severe obesity and its relationship with insulin resistance and excess body weight[J].Andrology,2016,4(1):62-67.
[51]Trachta P,DostálováI,HaluzíkováD,et al.Laparoscopic sleeve gastrectomy ameliorates m RNA expression of inflammation-related genes in subcutaneous adipose tissue but not in peripheral monocytes of obese patients[J].Mol Cell Endocrinol,2014,383(1-2):96-102.
[52]Fariello RM,Pariz JR,Spaine DM,et al.Association between obesity and alteration of sperm DNA integrity and mitochondrial activity[J].BJU Int,2012,110(6):863-867.
[53]Mah PM,Wittert GA.Obesity and testicular function[J].Mol Cell Endocrinol,2010,316(2):180-186.
[54]Duits FH,van Wely M,van der Veen F,et al.Healthy overweight male partners of subfertile couples should not worry about their semen quality[J].Fertil Steril,2010,94(4):1356-1359.
[55]Kratzsch J,Paasch U,Grunewald S,et al.Resistin correlates with elastase and interleukin-6 in human seminal plasma[J].Reprod Biomed Online,2008,16(2):283-288.