Polycystic ovary syndrome (PCOS) is a common comorbidity found in obese women of reproductive age. It is associated with significant clinical manifestations of menstrual irregularities, infertility and androgen excess. Bariatric surgery has been widely proven to be a successful management strategy for morbid obesity and metabolic syndrome, but limited studies exist on its effect on PCOS. To our knowledge, we are the first to systematically review the literature and perform a meta-analysis on the impact of bariatric surgery on PCOS.
To meet PCOS criteria, women must have a combination of hyperandrogenism, anovulation and ultrasound findings. Almost 10% of all reproductive age women worldwide show signs of PCOS. Although women often seek care for gynecological or body image concerns, many PCOS women are at risk for metabolic syndrome (MS). Many of the metabolic consequences are overlooked and undertreated by physicians because these patients tend to be young, reproductive age women.
Bariatric surgery can be an effective means of weight loss in PCOS women. Surgical techniques have become safer and less invasive over time and have been found to be effective in achieving significant weight loss. Surgical options have also increased, giving patients more choices. Bariatric surgery may prevent or reverse metabolic syndrome. Bariatric surgery may also have reproductive benefits in PCOS patients. Although bariatric surgery has historically been performed in older, reproductive aged women, it has recently gained favor in adolescents as well. This is of particular importance due to the prevalence of both PCOS and MS in adolescents. Treatment of PCOS and MS certainly requires a combination of medical therapy, psychological support and lifestyle modifications. These treatments are difficult and often frustrating for patients and physicians. Bariatric surgery can be effective in achieving significant weight loss, restoration of the hypothalamic pituitary axis, reduction of cardiovascular risk and even in improving pregnancy outcomes. Ultimately, bariatric surgery should be considered part of the treatment in PCOS women, especially in those with MS.
The role of bariatric surgery in PCOS women will be reviewed with a focus on metabolic improvements. Since many adolescents have PCOS, the evidence, concerns and outcomes in this special patient population will be discussed. Finally, reproductive and pregnancy concerns will be summarized in order to gain a more complete perspective on the potential benefits and concerns of bariatric surgery in these women.
Metabolic consequences of pcos
PCOS women have a high prevalence of insulin resistance and impaired glucose tolerance, both precursors of diabetes mellitus. Insulin resistance is difficult to measure but more than 50% of PCOS women, even as adolescents, have insulin resistance and they progress commonly to MS. MS is defined as a grouping of characteristics predisposing to coronary artery disease and diabetes mellitus. MS requires 3 of the following: central obesity, elevated triglycerides, decreased high-density lipoprotein, hypertension and elevated fasting blood glucose. Its prevalence in the general population is 25% and in PCOS women is 40%-50%. The prevalence of MS is young PCOS women < age 40 years (45%-53%) is particularly high relative to age matched counterparts (6%-15%). Even male relatives of PCOS women have a higher incidence of MS. Young women with PCOS have more labile blood pressure regulation and even adolescents show blood pressure regulatory changes. Later in life, menopausal PCOS women have twice the prevalence of hypertension. Clinically, it is an oversimplification to believe that PCOS women just have a higher propensity for MS. PCOS itself may be pathophysiologically related to MS. Both gene and protein expression in omental tissue of PCOS women show differences compared to non-hyperandrogenic obese women, suggesting a direct causal connection between PCOS, visceral adiposity and ultimately MS. PCOS women consistently show elevated low-density lipoprotein and triglycerides, lower high-density lipoprotein, increased carotid intimal thickening and an increase in both fatal and non-fatal cardiovascular events. Forty percent of PCOS women have diabetes mellitus before the age of 50 years. These changes are not always dependent on body mass index (BMI).
Obesity is an epidemic
Despite universal recognition that weight control is important, it remains perhaps the most difficult morbidity to treat. Obesity is usually defined by BMI and has become the standard research and clinical tool in monitoring weight.The surrounding social environment, especially family attitudes and support for obese children and adolescents, greatly impacts the success of lifestyle modifications.Pharmacological treatments exist but are limited. Surgical weight loss has been an option for many years but is underutilized, especially in younger patients whose risk factors for coronary artery disease are less glaring. The evidence for lifestyle modifications producing metabolic parameters in PCOS is disappointing.
Bariatric Surgery May Help Women with Polycystic Ovarian Syndrome Overcome Infertility
The procedure reduces androgen levels and ovarian size
Obese women have a higher incidence of Polycystic Ovarian Syndrome (PCOS), the most common cause of infertility in reproductive-age women. The disease is characterized by enlarged ovaries, higher androgen levels and irregular menstrual cycles, all of which can result in infertility.
Bariatric surgery has been available for decades. Most procedures are now performed laparoscopically. Although various procedures have been described and attempted, the 3 most common procedures performed are laparoscopic adjustable gastric banding (LAGB), laparoscopic roux-en-Y gastric bypass (LRYGB) and laparoscopic sleeve gastrectomy (LSG). LAGB involves a band around the proximal stomach which can be progressively inflated and tightened via a subcutaneous port. LRYGB involves surgical diversion of a smaller pouch of stomach to the jejunum. The length of diversion is related to the expected magnitude of effect. Morbidity and mortality in general is inversely proportional to both hospital and surgeon volume. Bariatric surgery is cost effective in comparison to the excessive cost of medical care in these patients for metabolic abnormalities, especially diabetes mellitus.
Risks of bariatric surgery
Both short and long term risks of surgery in general have declined over time. Complications are purported to be lower because it does not include any surgical bypass and avoids implantation of any device.
Minimally invasive surgical options
Almost all bariatric procedures are now performed laparoscopically due to decreased surgical time, shorter hospital stay and quicker recovery. A significant number of procedures are now performed with robotic assistance. Due to improved visualization, increased accuracy and positioning, it is certainly plausible that robotic assistance will significantly reduce morbidity and surgical complication rates.
Metabolic improvements after bariatric surgery
Bariatric surgery ameliorates metabolic abnormalities. As noted above, BMI and excess body weight decrease substantially after surgery. More importantly, improvement is noted in glucose abnormalities, dyslipidemia and hypertension. Improvement in diabetes mellitus at 2 year follow up after surgery is proportional to weight loss. Proposed mechanisms include a beneficial alteration in incretin response via earlier and better GLP-1 effects, especially with bypass procedures. Insulin abnormalities may improve very early post-operatively in pre-menopausal women with MS. Fasting glucose and insulin resistance measured by the homeostasis model assessment insulin resistance (HOMA-IR) can decrease > 50% within 1 mo of surgery, whereas insulin sensitivity measured by the euglycemic-hyperinsulinemic clamp does not change as quickly. Additionally, these measurements parallel reduced leptin levels and increased adiponectin, resistin and ghrelin, indicating biochemical explanation for the success of surgery. Both LRYGB and LGB decrease HOMA-IR, normalize lipid parameters and decrease leptin by 50% immediately post-operatively. Recently, a prospective controlled clinical trial compared intensive lifestyle intervention to LRYGB over a one year period.
PCOS presents a unique challenge since many obese PCOS women are adolescents. Bariatric surgery may actually provide primary prevention of coronary artery disease, eliminate MS and cause meaningful, long term reduction in morbidity and mortality. So, even some PCOS women aged 25-40 years with MS probably already have early coronary artery disease and thus are no longer candidates for primary prevention. Of course, a comprehensive approach to weight loss in adolescents is very important. Almost 20% of adolescents are overweight by the age of 19 years. It is very important for young women to initiate diet and exercise. Pharmacological treatments are also an option for adolescent obesity, although data are limited.
Reproductive considerations for bariatric surgery
Reproductive concerns may also lead PCOS women with MS to consider bariatric surgery. Does surgery optimize both fertility and pregnancy? The relationship between PCOS, obesity and infertility has been documented for many years. Known effects include anovulation, miscarriage, impairment in folliculogenesis and altered endometrial receptivity. Modest weight loss often increases the odds of spontaneous ovulation. At the current time and with current surgical risks, bariatric surgery should not be considered a “fertility treatment” for ovulation induction. However, pregnancy risks in woman with MS are high. These women face difficulty in managing diabetes, pre-eclampsia, growth disorders, higher rates of cesarean delivery, higher maternal mortality and increase their children’s risks for metabolic disease in the future.
PCOS women have less hyperandrogenism post operatively and sex hormone binding globulin increases after bariatric surgery. LH and FSH levels have been reported to increase after surgery. On a more functional level, ovulatory function measured by luteal LH and progesterone secretion improved postoperatively, although levels were still below normal expected values. Additionally, leptin levels decrease after bariatric surgery, reflecting improved reproductive metabolic status.
PCOS, hirsutism, and menstrual irregularities improve after bariatric surgery.