This column is written by medical students and is dedicated to reviewing the science behind obesity and bariatric surgery.
Column Editor: Daniel B. Jones, MD, MS, FASMBS
Professor of Surgery, Harvard Medical School, Vice Chair, Beth Israel Deaconess Medical Center, Boston, Massachusetts
This month: Bariatric Surgery, Hypogonadism, and Improvement in Sexual Function
by Fan Di Xia
Medical Student, Harvard Medical School, Boston, Massachusetts
Hypogonadism and sexual dysfunction are associated with obesity. Evidence suggests that obesity suppresses the hypothalamic-pituitary-gonadal (HPG) axis in a number of ways. Weight loss after bariatric surgery has been found to reverse obesity-associated hypogonadism and improve sexual function in both men and women. Further studies are needed to demonstrate the individual relationship between reversal of hypogonadism and improvement in sexual function.
Bariatric Times. 2016;13(2):12–13.
Driven by the growing prevalence of obesity and the large body of evidence on the medical benefits of weight loss surgery, the number of bariatric procedures performed in the United States rose from 13,365 in 1998 to 179,000 in 2013.[1–2] Data show that the reduction in adipose tissue associated with bariatric surgery significantly alters the body’s metabolic axes to lower risk factors for cardiovascular, endocrine, and gastrointestinal diseases, including hypertension, diabetes mellitus, and obstructive sleep apnea.[3,4] Among the metabolic axes, obesity has been linked with hypogonadism and sexual dysfunction in both men and females.[5,6] This article reviews the relation between obesity and the hypothalamic-pituitary-gonadal (HPG) axis, and the effect of bariatric surgery on obesity-related hypogonadism and sexual dysfunction.
Obesity and the Hypothalamic-Pituitary-Gonadal (HPG) AXIS
The HPG axis consists of the hypothalamus, which secretes gonadotropin releasing hormone (GnRH) pulses that trigger the pituitary to release gonadotropins LH (lutenizing hormone) and FSH (follicle stimulating hormone). In males, LH stimulates testosterone production, and FSH contributes to the initiation and maintenance of spermatogenesis. In females, FSH stimulates recruitment of ovarian follicles that lead to the production of estradiol and progesterone. Together with FSH and LH, these hormones contribute to the female reproductive and menstrual cycle. In most circumstances, negative feedback from estradiol and testosterone to the pituitary and the hypothalamus decreases GnRH, FSH, and LH secretion.[7,8]
Sexual function in males and females is an intricate process consisting of desire (libido), arousal (e.g., genital vasocongestion), orgasm, and resolution. Sex hormones play a complex role in this process. Male sexual dysfunction includes erectile dysfunction, premature ejaculation, and decreased libido; female sexual dysfunction includes decreased libido, impaired arousal, anorgasmia, and dyspareunia.[9,10] Normal sexual function involves interactions between hormonal, neurologic, vascular, and psychological systems. From a hormonal perspective, testosterone plays a significant role in male sexual function. It is integral to arousal and the ability to produce and maintain an erection.
Studies show that testosterone deficiency in males results in impotence, while the restoration of testosterone restores erectile function. In females, it is still unclear whether physiologic concentrations of testosterone/androgens play a significant role, if any at all, in sexual function.[12,13] Rather, estrogen is the major factor contributing to vulvovaginal lubrication, genital vasoconstriction, maintenance of vaginal lining, and minimization of sexual pain.[13,14]
Several factors are posited as the mechanisms by which obesity contributes to suppression of the HPG axis (Figure 1). First, the aromatase activity present in adipocytes converts testosterone into estradiol; estradiol in turn, through negative feedback, decreases GnRH, LH, and FSH secretion. Androgens are necessary for the maintenance of muscle mass; without androgens, adipose tissue replaces muscle, further exacerbating obesity-induced hypogonadism. Second, elevated levels of serum leptin in males with obesity may suppress testicular androgen production and leydig cell sensitivity to LH stimulation. In addition, obesity-related release of inflammatory mediators, such as TNF-α and IL-1β, suppress the HPG axis.15 Third, obesity-associated disruption in sleep, via comorbidities such as obstructive sleep apnea (OSA), interferes with nocturnal LH secretion, potentially contributing to obesity-associated hypogonadism.
Studies suggest that hypogonadism and obesity are strongly associated; that the decreases in testosterone levels are inversely proportional to increases in BMI. For example, in a study of 1,849 males, 40 percent of patients with obesity 45 years or older (BMI ≥ 30kg/m2) had subnormal levels of testosterone. Females with obesity have relative hypogonadism. A study comparing LH levels pre and post GnRH stimulation in obese versus normal-weight females found that both pre and post-stimulation LH levels were significantly lower in patients with obesity.
Obesity-related reduction in sex hormones may contribute to impaired sexual function. In a study on sexual function before and after Roux-en-Y gastric (RYGB) bypass in 97 males, Dallal et al21 found that subjects with obesity had significantly worse sexual function in terms of sex drive, erectile dysfunction, ejaculatory function, and sexual satisfaction compared with age-matched non-obese controls. In a study of 102 females with obesity, Bond et al found that 60% of the group had impaired sexual function as measured by the Female Sexual Function Index (FSFI). The FSFI is a validated instrument that assesses six domains of sexual function including sexual desire, arousal, lubrication, orgasm, and satisfaction.
Sexual impairment in individuals with obesity is likely multifactorial, involving both psychological and physical biologic factors. Few studies have isolated the relationship between sexual dysfunction and reduced hormones in obesity. However, reports indicate that the reversal of hypogonadism after bariatric surgery is associated with improved in sexual function.[5,21,23]
Bariatric Surgery and the Reversal of Hypogonadism
Various studies have investigated the effect of bariatric surgery in reversing obesity-associated hypogonadism. In a meta-analysis of 24 studies on bariatric surgery versus low-calorie diet in reversing male obesity-associated hypogonadism, Corona et al found that both bariatric surgery and lifestyle modification resulted in significant increases in bound and unbound testosterone levels, increased gonadotropin levels (FSH, LH), and a decrease in estradiol. However, bariatric surgery was more effective at increasing testosterone levels compared with dietary modification. This outcome likely reflects the greater degree of weight loss with bariatric surgery versus dietary modification (32% vs. 9.8%). A study of male sexual function after bariatric surgery also showed a significant improvement in erectile function.
Similarly, a prospective cohort study found that in 106 women who underwent bariatric surgery (85 RYGB, 21 laparoscopic adjustable gastric banding), the group lost a mean of 33.5 percent of initial body weight at two years, with a significant increase in all sexual hormones of interest: estradiol, total testosterone, FSH, LH, sex-hormone binding globulin (SHBG), and dehydroepiandrosterone sulfate (DHEA-S). The patients also experienced improvement in all domains of sexual function—including arousal, lubrication, desires, and satisfaction.
These data demonstrate that bariatric surgery is effective at reversing obesity-related hypogonadism, and that it leads to an improvement in sexual function in both males and females. Sexual function is a complex process that includes hormonal, vascular, neuronal, and psychological influences. Thus, the effect of weight loss surgery on improving sexual function is most likely multifactorial, mediated not only by hormonal restoration, but also by psychological improvements in such domains as body image. More research is required to better demonstrate the individual relations between post-bariatric changes in specific biologic variables with improvements in sexual function. Nonetheless, the effect of bariatric surgery on the reversal of hypogonadism and improvement of sexual function is notable, serving as another point for discussion when evaluating a patient for bariatric surgery.
1. American Society for Metabolic and Bariatric Surgery. New Procedure Estimates for Bariatric Surgery: What the Numbers Reveal. 2014, May. http://connect.asmbs.org/may-2014-bariatric-surgery-growth.html. Accessed December 28, 2015.
2. Santry HP, Gillen DL, Lauderdale DS. Trends in bariatric surgical procedures. JAMA. 2005;294(15):1909–1917.
3. Noria, SF, Grantcharov T. (2013). Biological effects of bariatric surgery on obesity-related comorbidities. Can J Surg. 2013;56(1):47–57.
4. Schroeder R, Garrison JM Jr, Johnson MS. Treatment of adult obesity with bariatric surgery. Am Fam Physician. 2011;84(7):805–814.
5. Sarwer DB, Spitzer JC, Wadden TA, et al. Changes in sexual functioning and sex hormone levels in women following bariatric surgery. JAMA Surg. 2014;149(1):26–33.
6. Corona G, Rastrelli G, Monami M, et al. Body weight loss reverts obesity-associated hypogonadotropic hypogonadism: a systematic review and meta-analysis. Eur J Endocrinol. 2013;168(6):829–843.
7. Bhasin S, Jameson J. Disorders of the testes and male reproductive system. In Kasper D, Fauci A, Hauser S, Longo D, Jameson J, Loscalzo J (eds). Harrison’s Principles of Internal Medicine, 19e. New York, New York: McGraw-Hill; 2015.
8. Hall JE. Disorders of the female reproductive system. In Kasper D, Fauci A, Hauser S, Longo D, Jameson J, Loscalzo J (eds), Harrison’s Principles of Internal Medicine, 19e. New York, New York: McGraw-Hill; 2015.
9. Sexual dysfunctions. In: Diagnostic and Statistical Manual of Mental Disorders, 5th ed. American Psychiatric Association, Arlington, Virginia; 2013.
10. Diaz VA, Close JD. Male sexual dysfunction. Prim Care. 2010;37(3):473–489, vii–viii.
11. Bancroft J, Wu FC. Changes in erectile responsiveness during androgen replacement therapy. Arch Sex Behav. 1983;12(1):59–66.
12. Santoro N, Torrens J, Crawford S, et al. Correlates of circulating androgens in mid-life women: the study of women’s health across the nation. J Clin Endocrinol Metab. 2005;90(8):4836–4845.
13. Dennerstein L, Dudley EC, Hopper JL, Burger H. Sexuality, hormones and the menopausal transition. Maturitas. 1997;26(2):83–93.
14. Berman JR, Berman LA, Werbin TJ, Goldstein I. Female sexual dysfunction: anatomy, physiology, evaluation and treatment options. Curr Opin Urol. 1999;9(6):563–568.
15. Dandona P, Dhindsa S. Update: hypogonadotropic hypogonadism in type 2 diabetes and obesity. J Clin Endocrinol Metab. 2011;96(9):2643–2651.
16. Saad F, Gooren LJ. The role of testosterone in the etiology and treatment of obesity, the metabolic syndrome, and diabetes mellitus type 2. J Obes. 2011;2011. pii: 471584.
17. Isidori AM, Caprio M, Strollo F, et al. Leptin and androgens in male obesity: evidence for leptin contribution to reduced androgen levels. J Clin Endocrinol Metab. 1999;84(10):3673–3680.
18. Luboshitzky R, Lavie L, Shen-Orr Z, Herer P. Altered luteinizing hormone and testosterone secretion in middle-aged obese men with obstructive sleep apnea. Obes Res. 2005;13(4):780–786.
19. Dhindsa S, Miller MG, McWhirter CL, et al. Testosterone concentrations in diabetic and nondiabetic obese men. Diabetes Care. 2010;33(6):1186–1192.
20. Roth LW, Polotsky AJ, Bradford AP, et al. Relative hypogonadism in obese women is explained by a blunted pituitary response to GnRH. The Endocrine Society’s 94th Annual Meeting and Expo, June 23–26, 2012. Houston, Texas.
21. Dallal RM, Chernoff A, O’Leary MP, et al. Sexual dysfunction is common in the morbidly obese male and improves after gastric bypass surgery. J Am Coll Surg. 2008;207(6):859–864.
22. Bond DS, Vithiananthan S, Leahey TM, et al. Prevalence and degree of sexual dysfunction in a sample of women seeking bariatric surgery. Surg Obes Relat Dis. 2009;5(6):698–704.
23. Reis LO, Favaro WJ, Barreiro GC, et al. Erectile dysfunction and hormonal imbalance in morbidly obese male is reversed after gastric bypass surgery: a prospective randomized controlled trial. Int J Androl. 2010;33(5):736–744.
24. Saboor Aftab SA1, Kumar S, Barber TM. The role of obesity and type 2 diabetes mellitus in the development of male obesity-associated secondary hypogonadism. Clin Endocrinol (Oxf). 2013;78(3):330–337.
FUNDING: No funding was provided.
FINANCIAL DISCLOSURES: The author reports no conflicts of interest relevant to the content of this article.