Benefits of GLP-1s for Insulin Resistant PCOS
Explore the connection between GLP-1 and PCOS
The hormonal disorder polycystic ovary syndrome (PCOS) can greatly affect one’s quality of life. Not only can it cause infertility in women, but it’s also associated with weight gain, irregular menstruation, acne, and more. '
Admittedly, PCOS still isn’t well understood, but research has shed light on its connection to poor metabolic health. To counteract its effect, patients are often encouraged to make lifestyle changes, but what happens when that doesn’t seem like enough?
GLP-1 analogs, known for their antidiabetic and weight loss abilities, are gaining attention as a potential treatment for PCOS. Below, we’ll provide insight into common metabolic problems impacting PCOS patients. Then, we’ll explain what's been discovered about GLP-1 and PCOS management so far.
Understanding metabolic impairment in PCOS
As the most frequent endocrine disease, PCOS has a prevalence between 6% and 20% in women of reproductive age. In addition, of those with PCOS, over 40% of adult women and almost one-third of teenagers have metabolic syndrome.
Metabolic syndrome refers to having a cluster of conditions that raise one’s risk of stroke, cardiovascular disease, and type 2 diabetes. For clarity, those conditions are:
High blood triglycerides and low-density lipoprotein (LDL) levels
Low high-density lipoprotein (HDL) cholesterol
Elevated blood sugar levels
Abdominal obesity
High blood pressure
The four clinical features of PCOS could be considered metabolic syndrome, which we’ll discuss below.
1. Hyperandrogenism
Also regarded as one of the PCOS diagnosis criteria, hyperandrogenism is a medical ailment where the body produces excess amounts of androgens. These male sex hormones regulate body fat distribution and influence fat tissue accumulation in the abdominal region. When there are elevated amounts of it, individuals could develop insulin resistance, secondary hyperinsulinemia (abnormally high levels of insulin), sodium retention, high blood pressure, and more.
2. Insulin resistance
The relationship between insulin resistance and PCOS is multi-layered. For one, having PCOS increases one's risk of type 2 diabetes.
Unregulated insulin also boosts excessive ovarian androgen production, which, as we mentioned before, causes numerous issues.
Furthermore, it diminishes the circulating amount of sex hormone-binding globulin (SHBG), a protein that binds to and transports sex hormones in the bloodstream. This can cause irregular menstruation and female sexual dysfunction.
3. Abdominal obesity
Approximately 60% of women diagnosed with PCOS struggle with obesity, compared to just 35% of those in the general female population. It can worsen insulin resistance and hyperinsulinemia. Carrying excess weight may even cause relative hyperandrogenemia by boosting free-form testosterone production.
4. Dyslipidaemia
Having abnormal amounts of lipids in the blood is called dyslipidemia. This condition is prevalent in PCOS patients, accounting for approximately 70% of them. Usually, it presents as elevated levels of free fatty acid, triglycerides, and LDL cholesterol, along with diminished concentrations of HDLs.
Research finds that dyslipidemia negatively influences the long-term health outcomes of women with PCOS, heightening their risk of non-fatal cerebrovascular disease events.
GLP-1s and PCOS: How did we get here?
Initially FDA-approved to manage type 2 diabetes, glucagon-like peptide-1 (GLP-1) agonists are now believed to offer multifaceted benefits. While the idea of implementing them in PCOS treatment might initially seem far-fetched, research has shown positive results. Plus, it’s not the first diabetes-based drug to be studied for disease management.
As one study pointed out, connecting PCOS to insulin resistance, which is often piqued by obesity-induced insulin resistance, opened the door for trials of obesity drugs in PCOS.
Initially, studies were done on metformin®, which showed that it could decrease weight by up to 5% when combined with lifestyle interventions. Researchers noted that Metformin improved some of the clinical features of PCOS mentioned before, like hyperandrogenism and insulin resistance. Not only that, patients experienced better menstrual function and fertility.
After seeing these results, researchers naturally wanted to see how other weight loss pharmacology solutions, like GLP-1s, might perform.
The potential benefits of GLP-1s for PCOS treatment
So, what has current research shown us about the effect that GLP-1s have on PCOS? It turns out that it can offer many advantages, which we’ll dive into below.
Pregnancy rates
So far, two studies have assessed pregnancy rates in patients with PCOS. In one study, patients were given either metformin or exenatide, a type of GLP-1 drug, for twelve weeks, followed by just metformin for the second twelve weeks.
The group who initially received exenatide had a much higher rate of natural pregnancy than the metformin one.
The other study evaluated women with PCOS taking low-dose liraglutide along with metformin. Researchers discovered that those taking liraglutide and metformin had better results than those who only took metformin.
The combination group saw increased in vitro fertilization and cumulative pregnancy rates following pre-treatment in women who were previously resistant to reproductive treatment.
Menstrual cycle regularity
Women with PCOS usually have less than six to eight menstrual periods annually, likely due to irregular ovulation. However, it’s possible that GLP-1s could help with this, too.
One study showed that overweight women diagnosed with PCOS experiencing infrequent or irregular ovulation noted better ovulation rates when using exenatide. It is believed that weight loss influenced by the GLP-1 drug is the primary reason behind this.
Cardiovascular health
There’s a correlation between PCOS and adverse cardiovascular risk, in which insulin resistance is a leading factor. Women with PCOS have a 30% greater risk of cardiovascular disease, but recent studies evaluating GLP-1 drugs show some promise.
A 6-month controlled study assessed how taking liraglutide daily would affect weight loss and atherothrombosis markers in women with PCOS. They discovered that those receiving the GLP-1 treatment saw a remarkable decrease in atherothrombosis markers, like clotting, inflammation, and endothelial dysfunction.
In another study, liraglutide led to a decline in cardiovascular risk biomarkers for cardiovascular disease. Participants also saw a decrease in visceral adipose tissue and liver fat content.
Weight loss
By now, you’ve likely noticed that GLP-1 medications have gained considerable attention for their role in weight management. Since many PCOS patients struggle with obesity, research shows that weight loss can offer them several benefits, regardless of the condition's clinical phenotype and pathophysiological pathways.
These medications encourage weight loss in several ways, such as:
Glucagon secretion suppression
Decreased hunger
Appetite regulation
Satiety
Delayed gastric emptying
Reducing energy intake
Stimulates insulin production
There have been numerous small studies evaluating women with PCOS who are also overweight or obese following GLP-1 treatment. Occasionally, these therapies are combined with metformin. A meta-analysis, including 23 studies, discovered that liraglutide monotherapy performed better at decreasing waist circumference and body weight in PCOS women than other approaches.
GLP-1 medications for PCOS treatment
The significant impact of metabolic dysfunction in women with PCOS cannot be ignored. Patients with this condition often have a diminished quality of life due to the toll it takes on them physically.
However, it’s not uncommon for patients with PCOS to experience mental health issues like anxiety and depression as well. Symptoms like excess body hair, acne, and thick skin patches may interfere with one's self-esteem, causing women to become reclusive.
Virtual care offers discreet, convenient treatment for sexual health
Often, this population may avoid treatment because they fear being judged by peers. This is also seen in patients experiencing other sexual health disorders or dysfunctions.
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