Polycystic ovarian syndrome (PCOS) is an endocrine disorder that causes an increase in androgen hormone production in women. It affects 5 -10% of premenopausal women, and genetics play a large role in whether you have PCOS.
No one gene causes PCOS, but there are genetic variants in several hormonal pathways that increase the risk for it. Researchers estimate that PCOS is about 70% heritable.[ref] Understanding which genetic variants you carry may help you figure out the most effective way for you to manage your PCOS. Members will see their genotype report below, plus additional solutions in the Lifehacks section. Join today.
Symptoms of PCOS
PCOS symptoms include irregular menstrual cycles, high androgen hormones, and cysts in the ovaries. Other hallmarks of PCOS include weight gain, insulin resistance, and elevated luteinizing hormone (LH) levels.[ref]
The excess of androgen hormones may cause facial or back hair as well as male pattern baldness. Skin problems include hormonal acne.
PCOS is a ‘syndrome’, meaning that not all symptoms have to be present to have PCOS.
Also, not everyone with PCOS has ovarian cysts — and not everyone with ovarian cysts has PCOS.[ref]
Let’s take a deep dive into what causes PCOS… and then look at your specific genetic susceptibility.
The three main physiological changes that we will look at include:
- hormone dysregulation
- insulin resistance and hyperinsulinemia
- circadian rhythm changes
Hormonal Dysregulation in PCOS:
Before diving into what goes wrong with PCOS, let’s first look at the hormonal processes that generally go on during a menstrual cycle.
The start of menstruation (your period) is considered the beginning of the menstrual cycle. Estrogen and progesterone levels are both low at this point.
Follicle-stimulating hormone (FSH) rises a bit, causing the development of the new follicle (containing an egg) in the ovary. The follicle produces estrogen, causing estrogen to rise over the next week.
Around day 12 – 14, ovulation occurs, releasing the egg. During ovulation, the pituitary gland releases luteinizing hormone (LH) and FSH at higher levels. This spike in LH and FSH hormone levels coincides with a fall in estrogen levels and an increase in progesterone. The follicle that has released the egg cell will form a corpus luteum, a hormone-secreting structure that produces high levels of progesterone.
What does your body need to make all these reproductive hormones? The molecular basis for these steroid hormones is cholesterol, which is converted into pregnenolone, which is the precursor for other hormones.
There are two ways that pregnenolone can be converted into other hormones. The enzyme CYP17A1 can eventually convert pregnenolone into DHEA. Alternatively, the enzyme 3B-HSD can convert pregnenolone into progesterone.
DHEA can then be converted into testosterone or other androgens — or it can convert to estrone and other estrogens.
Insulin resistance and androgen hormone production:
A number of different hormone pathways can be involved in PCOS. Androgen hormones in women usually convert to estrogen. Higher estrogen levels feedback to the pituitary gland, causing an increase in LH (luteinizing hormone) during ovulation.[ref]
Thus, when levels of androgen hormones are too high and not appropriately converted to estrogen, it interferes with ovulation or the release of the egg. It causes what looks like cysts in the ovaries when the immature egg follicles aren’t released.
Women with PCOS often have problems with insulin resistance and higher blood glucose levels.
Insulin increases the production of androgens in women. For this reason, women’s increased testosterone levels show associations with insulin resistance. The system works both ways – giving women testosterone can increase insulin resistance. These hormones are all interrelated. In the ovaries, insulin stimulates the production of testosterone.[ref][ref]
About 20 – 30% of women with PCOS have high DHEA levels. DHEA is a precursor for androgens and estrogens.[ref]
Circadian rhythm disruption as a cause of PCOS:
New research shows that circadian rhythm disruption may play a key role in causing PCOS.[ref]
Quick aside: What is circadian rhythm?
Your circadian rhythm is the built-in 24-hour clock that drives many processes in the body. The first thing that pops to mind is your sleep/wake cycle, but your body’s circadian clock is far more than just sleep.
Over a 24-hour period, your body’s metabolic and cellular functions rise and fall. Some processes take place at night, and others during the day. For humans (and almost all animals), this 24-hour rhythm is synchronized by light.
Circadian rhythm disruption is tied to many chronic diseases, including obesity, heart disease, and dementia. Think about what jet lag feels like — your brain’s not working right, your stomach is not feeling right, and everything’s just out of sync.
Circadian disruption on a smaller scale happens each time you stay up later than usual in an area with bright lights. This shift is called social jetlag.
The body’s circadian clock is driving the rising and falling of some key proteins — and these oscillations are synchronized by light. Electric lighting has been around now for more than a century, but that is a drop in the bucket compared to the human and animal history of only having sunlight or firelight. Thus, it is easy to see how circadian rhythm disruption is a modern mismatch of lifestyle vs. innate biological function.
Back to PCOS:
Researchers have used animal models to show that circadian rhythm disruption can cause the same alterations to hormones as are seen in PCOS. For a couple of decades, it was known that altering circadian rhythm could alter insulin sensitivity and androgen production. But this new research lays out and produces the PCOS phenotype simply by altering circadian rhythm.
The researchers used changes in light to show that the alterations to the circadian clock genes caused the downstream effects on the hormones involved in PCOS.[ref]
Pregnancy with PCOS:
Women with PCOS are more likely to have problems with ovulation, which is a common cause of infertility.
In-vitro fertilization (IVF) is a common solution for PCOS infertility.[ref] There are also medications that your doctor can prescribe that alter your hormones at the right time in your cycle.
Overall statistics are hard to come by regarding the percentage of women with PCOS and infertility. Larger population studies point to women with PCOS being more likely to have fewer children but having similar overall fertility rates when looking only at women with 1 – 2 children.[ref]
Is PCOS reversible with diet?
Other medical-based websites claim that all you can do is manage the symptoms of PCOS and that there is no cure.[article]
I’ll add specific recommendations in the Lifehacks section below that integrate genetics with some research-based suggestions for diet, supplements, and exercise.
One thing that is not clear is whether weight loss (through whatever type of diet) will cure PCOS. A ‘risk factor’ for PCOS is obesity, so your doctor may tell you to lose weight. With this in mind, research points to weight gain is caused by PCOS instead of obesity as a cause of PCOS. Chicken or the egg.[ref]
Insulin sensitivity, rather than fad diets, may be better for managing PCOS through nutrition.
Hashimoto’s and PCOS:
Researchers have found autoimmune thyroid diseases, such as Hashimoto’s thyroiditis, at much greater levels in women with PCOS. Thus, if you or your doctor suspects that you have a thyroid problem, it is recommended to also test for autoimmune thyroid antibodies.[ref]
Related article: Thyroid hormones and your genes
PCOS Genotype Report
Not a member? Join here. Membership lets you see your data right in each article and also gives you access to the member’s only information in the Lifehacks sections.
Twin studies show that PCOS is about 70% hereditary, with the rest due to various environmental or dietary causes.
PCOS is considered an ‘evolutionary paradox’ since it is common (10% of the population), highly heritable, and also can cause infertility. Scientists want to know why the genetic variants involved in PCOS have continued to be passed on to a large part of the population – especially since evolutionary theory says that it should be weeded out. Some theories on this include that women with PCOS are more ‘metabolically thrifty’ and likely to live through a famine. Others theorize that women who only have a few children are better mothers and the children are more likely to survive.
Evolutionary theorizing aside, understanding which genetic variants you carry may help you to find the right solution for your PCOS symptoms.
LHCGR gene: luteinizing hormone receptor
Variants in the luteinizing hormone/choriogonadotropin receptor (LHCGR) gene are associated with an increased risk of PCOS and variations in the insulin response. The LHCGR is the receptor for both luteinizing hormone (LH), which triggers ovulation, and human chorionic gonadotropin (hCG), which maintains pregnancy.
Check your genetic data for rs13405728 (23andMe v4, v5; AncestryDNA)
- A/A: typical
- A/G: increased insulin levels in PCOS, but decreased overall risk of PCOS in Asian pops
- G/G: increased insulin levels in PCOS[ref], but decreased overall risk of PCOS in Asian pops.[ref]
Members: Your genotype for rs13405728 is —.
Check your genetic data for rs2293275 (23andMe v4, v5; AncestryDNA):
- T/T: increased risk (3 – 4-fold) of PCOS[ref][ref][ref]
- C/T: increased risk for PCOS
- C/C: typical risk of PCOS
Members: Your genotype for rs2293275 is —.
DENND1A gene: Androgen hormone synthesis
Too much DENND1A increases androgen hormone synthesis in the cells in the ovaries.
Check your genetic data for rs10818854 (23andMe v4, v5; AncestryDNA):
Members: Your genotype for rs10818854 is —.
FSHB gene: Follicle-stimulating hormone
The luteinizing hormone to follicle-stimulating hormone (LH:FSH) ratio is important in PCOS. Higher LH:FSH ratio can disrupt ovulation.
Check your genetic data for rs11031006 (23andMe v4, v5; AncestryDNA):
- A/A: increased LH levels[ref]
- A/G: increased LH levels
- G/G: typical LH levels
Members: Your genotype for rs11031006 is —.
FSHR gene: receptor for FSH
The FSHR gene codes for the follicle-stimulating hormone receptor.
Check your genetic data for rs6166 (23andMe v4, v5; AncestryDNA):
Members: Your genotype for rs6166 is —.
ADIPOQ gene: regulating insulin
Adiponectin (ADIPOQ) is created by fat cells and helps to regulate energy metabolism and insulin.
Check your genetic data for rs2241766 (23andMe v4, v5):
- T/T: increased (1.9x) risk of PCOS[ref]
- G/T: typical risk of PCOS
- G/G: typical risk of PCOS
Members: Your genotype for rs2241766 is —.
Check your genetic data for rs1501299 (23andMe v4, v5; AncestryDNA):
- T/T: decreased risk of PCOS[ref]
- G/T: typical risk of PCOS
- G/G: typical risk of PCOS
Members: Your genotype for rs1501299 is —.
MTNR1B gene: melatonin, insulin resistance, and circadian rhythm
The melatonin receptor 1B is part of regulating your body’s circadian rhythm. Melatonin is essential in regulating insulin release at night and can play a significant role in fasting glucose levels.
If you are under a doctor’s care, be sure to talk with your doctor before making any changes.
You may wonder which of the three areas below (circadian rhythm, diet, and lifestyle) are most important. I don’t think that research gives us definitive answers here. Instead, it may be that a combination of the three is important: get your circadian rhythm and sleep on track; dial in your diet so that insulin is regulated; do your best with the lifestyle changes.
Circadian rhythm alignment:
Circadian rhythm disruption may be at the heart of PCOS for many women. The question is: What can you do in our modern world to get your circadian rhythm back on track – without getting rid of electronics and electric lights in the evening?
- Supplementing with melatonin for six months decreased androgen levels and increased FSH levels in women with PCOS.[ref]
- One huge thing you can do to increase melatonin naturally and get your circadian rhythm on track is to block out blue light at night.
- Getting outside as early as possible in the morning will help set your circadian rhythm. And sunlight exposure during the day has been shown to help boost melatonin production the next night.
- Women with PCOS are twice as likely to have sleep disturbances, and LH levels are related to changes in the sleep/wake cycle. Some researchers theorize that circadian rhythm disturbances are part of the pathogenesis of PCOS.[ref][ref]
- Eating earlier and not snacking after dinner should help insulin resistance if you carry the MTNR1B variant.
PCOS Diet and Medications:
Control insulin levels:
Keeping insulin levels low can prevent the ovaries from overproducing testosterone. It is estimated that 50 – 70% of women with PCOS have some degree of insulin resistance.[ref]
How do you know if you have insulin resistance? Higher fasting blood glucose levels (100 – 125 mg/dL) several mornings in a row indicate insulin resistance and pre-diabetes. You can easily purchase a blood glucose meter at your local pharmacy or online and track your morning blood glucose levels for a week.
Metformin and diabetes drugs:
Metformin is a prescription drug for diabetes and pre-diabetes. Many studies have shown that it can help reduce elevated androgen levels in women with PCOS.[ref][ref][ref] Your doctor may have other suggestions for diabetic medications for PCOS as well.
A ketogenic diet or lower carb:
While there aren’t any trials on a ketogenic diet, there are articles on the internet promoting this as a way to control the symptoms of PCOS. In general, the ketogenic diet should keep insulin levels low, which is probably why it helps some people with PCOS.
A study shows that just lowering carbohydrates decreases insulin levels by 30% in obese women with PCOS.[ref]
Lifestyle changes for PCOS:
Avoid endocrine disruptors: BPA, found in plastics and thermally printed receipts, is an endocrine disruptor. As shown in several studies, BPA seems to interact with PCOS symptoms.
- A recent study found that “Our results showed that women with PCOS had significantly higher serum BPA concentrations than healthy controls … which correlated positively with serum total testosterone”.[ref]
- Other studies have shown similar results, such as PCOS women having more than double the average BPA levels as women without PCOS.[ref][ref]
- Avoid heating foods in plastic, drinking out of plastic bottles exposed to heat, and eating foods from cans lined with BPA.
Like most things, this is probably a balancing act between getting enough exercise vs. not going overboard and working out three times a day.
The rest of this article is for Genetic Lifehacks members only. Consider joining today to see the rest of this article.
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Updated May 15, 2020
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering and also an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.