Metabolic Surgery vs. Medical Treatment Improves Libido and Testosterone Levels

By Sangeeta Kashyap, MD

Male hypogonadism is a frequent complication of obesity and type 2 diabetes. Up to one-third of patients with type 2 diabetes experience low libido and have subnormal total and free testosterone levels. Although the etiology remains unclear, impairments in testosterone levels have been associated with abdominal obesity, insulin resistance and subclinical inflammation.

Treatment with chronic testosterone replacement therapy is associated with modest improvement of symptoms (libido, mood), quality of life and improvement of cardiometabolic parameters in the diabetic population. Modest weight loss of at least 10 to 15 percent and use of certain insulin sensitizers also have been reported to lead to improvements in testosterone levels. However, achieving durable weight loss is difficult for many patients, particularly those with type 2 diabetes controlled with insulin-providing agents.

Bariatric or metabolic surgery is a potent therapy for type 2 diabetes in the setting of moderate and severe obesity, supported by publication of three randomized controlled trials, including one that was conducted at Cleveland Clinic. In those three studies, bariatric surgery was more effective than medical therapy to restore glycemic control in obese patients with type 2 diabetes.

In a subset of patients in one trial, we recently demonstrated potent metabolic effects of both sleeve gastrectomy and Roux-en-Y gastric bypass operations on insulin secretion, sensitivity and reduction of abdominal adiposity. Therefore, we hypothesized that bariatric surgery can effectively reverse male hypogonadism in patients with moderate obesity and poorly controlled type 2 diabetes and may present an alternative strategy to chronic testosterone supplementation.

STAMPEDE subset studied

We performed an ancillary analysis to the Cleveland Clinic-led Surgical Treatment and Medications Potentially Eradicate Diabetes Effectively (STAMPEDE) trial in 42 men (aged 49 ± 8 years) with moderate obesity (BMI = 37 ± 3 kg/m2) and poorly controlled diabetes mellitus (HbA1c = 9.2 ± 1.4 percent) that were randomized to medical therapy alone (MT; n = 14), gastric bypass (RYGB; n = 17) or sleeve gastrectomy (SG; n = 11) plus medical therapy.

Total and free testosterone (ultrafiltration), sex hormone binding globulin (SHBG) and luteinizing hormone (LH) levels were determined at randomization and at 12-month follow-up and correlated with metabolic parameters and adiposity measures (DXA, leptin levels in a subset of n = 19).

Less low libido, higher testosterone

At 12 months, total body weight decreased by 5 percent in the MT group, 26 percent in gastric bypass and 27 percent in SG. Glycemic (HbA1c) levels reduced after all interventions: –1.6 percent in MT, –2.6 percent in SG and –3.2 percent in RYGB.

Low libido was less frequently reported following metabolic surgery (21 percent vs. 56 percent at baseline) than in patients receiving MT (40 percent vs. 50 percent at baseline). Median percent increase and absolute change in free testosterone levels were greater in RYGB vs. MT (49 percent vs. 6 percent, P = 0.05) and (32.8 vs. 4.2 pg/mL, P = 0.05) respectively; and were not different between SG and RYGB (59 percent vs. 49 percent; P = NS). The median percent increase in SHBG levels was 71 percent in SG and 110 percent in RYGB vs. 14 percent in MT. LH levels were similar at baseline and did not change at 12 months among the three groups.

The increase in free testosterone levels strongly related to the decrease in body weight (r = –0.36, P = 0.02), HBA1c (r = –0.32, P = 0.04), leptin (r = –0.52, P = 0.02), and truncal fat (r = –0.57, P = 0.009), but not with CRP levels (r = –0.23, P = 0.3).

We presented these study results at the 49th Annual Meeting of the European Association for the Study of Diabetes.

Clinical implications

Surgically induced weight loss improves symptomatic male hypogonadism in moderately obese males with type 2 diabetes to a greater extent than medical anti-diabetic therapy. The improvement in free testosterone is linked to better glucose control and loss of truncal fat. Mechanistic studies to investigate these associations are warranted.

Given that the typical cohort seeking bariatric surgery has consisted primarily of young, severely obese females, these data have major clinical implications for the use of bariatric surgery for obese men with type 2 diabetes. Moreover, given that androgen deficiency increases the risk for central obesity, insulin resistance and metabolic syndrome, restored testosterone levels following metabolic surgery may contribute long term to diabetes remission status, cardiovascular risk protection and improved quality of life.

Dr. Kashyap is an endocrinologist in the Endocrinology & Metabolism Institute and Associate Professor of Medicine at Cleveland Clinic Lerner College of Medicine. She is co-principal investigator of the STAMPEDE trial along with Philip Schauer, MD, Director of Cleveland Clinic’s Bariatric and Metabolic Institute.