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 plays a large role in whether you have PCOS. There is no one gene that causes PCOS, but there are genetic variants in several hormonal pathways that increase the risk for it.
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’, which means that all of the symptoms may not be present in any one person. Also, not everyone with PCOS has ovarian cysts, and not everyone with ovarian cysts has PCOS. [ref]
Before we dive into what goes wrong in PCOS, let’s first take a look at the hormonal processes that normally go on during a menstrual cycle.
The start of menstruation (period), when the lining of the uterus breaks broken down and sheds, marks 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 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, which is a hormone-secreting structure that produces high levels of progesterone.
What does your body need in order to make all these reproductive hormones? The molecular basis for these steroid hormones is cholesterol, which is converted into pregnenolone. The enzyme CYP17A1 can convert pregnenolone eventually into DHEA. Alternatively, the enzyme 3B-HSD can convert pregnenolone into progesterone. The molecular basis for these steroid hormones is cholesterol converts into pregnenolone.
DHEA can then be converted into testosterone or other androgens, or it can convert to estrone and other estrogens.
What goes wrong in PCOS?
A number of different hormone pathways can be involved here. 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. This causes what looks like cysts in the ovaries when the immature egg follicles aren’t released.
Quite often, women with PCOS 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 will stimulate the production of testosterone. [ref][ref]
About 20 – 30% of women with PCOS have high DHEA levels. DHEA is a precursor for the androgens and estrogens. [ref]
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 as far as the percentage of women with PCOS and infertility. Larger population studies point to women with PCOS being more likely to have fewer children, but yet having similar rates of overall fertility when looking only at women with 1 – 2 children. [ref]
There are a lot of websites that claim to have a dietary solution for PCOS symptoms. Most focus on healthy foods, and some claim a ketogenic diet works. [article][article] 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 as being caused by PCOS instead of obesity as a cause of PCOS. Chicken or the egg. [ref] Insulin sensitivity may be a better goal for managing PCOS through diet.
Twin studies show that PCOS is about 70% due to genetics, with the rest due to 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 when evolutionary theory says that it should be weeded out. Some of the 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 that you carry may help you to find the right solution for your PCOS symptoms.
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)
Check your genetic data for rs2293275 (23andMe v4, v5; AncestryDNA):
Too much DENND1A increases androgen hormone synthesis in the cells in the ovaries.
Check your genetic data for rs10818854 (23andMe v4, v5; AncestryDNA):
Follicle-stimulating hormone gene. The LH:FSH ratio is important in PCOS.
Check your genetic data for rs11031006 (23andMe v4, v5; AncestryDNA):
The FSHR gene codes for the follicle-stimulating hormone receptor.
Check your genetic data for rs6166 (23andMe v4, v5; AncestryDNA):
Adiponectin (ADIPOQ) is created by fat cells and helps to regulate energy metabolism and insulin.
Check your genetic data for rs2241766 (23andMe v4, v5):
Check your genetic data for rs1501299 (23andMe v4, v5; AncestryDNA):
The melatonin receptor 1B is a part of the regulation of your body’s circadian rhythm. Melatonin is important in the regulation of insulin release at night and can play a big role in fasting glucose levels.
Check your genetic data for rs10830963 (23andMe v4, v5; AncestryDNA):
If you are under a doctor’s care, be sure to talk with your doctor before making any changes.
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 are indicative of insulin resistance and pre-diabetes. You can easily purchase a blood glucose meter at your local pharmacy or online.
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 of diabetic medications for PCOS as well.
Berberine is often talked about as a natural alternative to metformin. It is a compound found in barberry and Oregon grapes. Some randomized clinical trials have found that it is as effective as metformin for PCOS. [ref][ref]
Melatonin and circadian rhythm:
Supplementing with melatonin for 6 months was found to decrease androgen levels and increase FSH levels in women with PCOS. [ref]
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 disturbance is part of the pathogenesis of PCOS. [ref][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.
Eating dinner earlier and not snacking after dinner should help with insulin resistance if you carry the MTNR1B variant.
Inositol helps to sensitize the body to insulin. Myoinositol was shown in one study to be the most effective form of inositol for women with PCOS and metabolic problems, while D-chiro-inositol was found to be most effective at reducing the symptoms of high androgen. [ref] Both myoinositol and D-chiro-inositol are found in health food stores and online.
Both animal and human studies have shown that resveratrol helps (some) in improving insulin resistance in PCOS. [ref] Resveratrol has also shown to lower testosterone levels (perhaps through insulin). [ref]
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.
There is a study showing that just lowering carbohydrates (and replacing those calories with omega-3/6 fats) decreases insulin levels by 30% in obese women with PCOS. [ref]
The amino acid l-carnitine has shown to help increase ovulation and pregnancy rates in women with PCOS. [ref] Carnitine supplementation helps out with depression in women with PCOS. [ref] A randomized controlled trial found that 250mg carnitine for 12 weeks reduced weight, and fasting plasma glucose in women with PCOS. [ref]
A randomized, placebo-controlled trial of 200mg/day of selenium showed that it decreased insulin levels in women with PCOS. [ref] Selenium, found in abundance in Brazil nuts, can be purchased as a supplement.
Supplements you may want to avoid with PCOS:
Avoid endocrine disruptors:
BPA, found in plastics and thermal printed receipts, is an endocrine disruptor. 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 have more than double the average BPA levels as women without PCOS. [ref][ref] Avoid heating foods in plastic, drinking out of plastic bottles that have been exposed to heat, and eating foods from cans lined with BPA. Basically, avoiding prepackaged foods and eating more whole foods will help you reduce your BPA exposure.
Exercise decreases the expression of 5-alpha-reductase in an animal model of PCOS. [ref] It has also been found to improve insulin sensitivity [ref] and overall metabolic health. [ref] Like most things, this is probably a balancing act, though, between getting enough exercise vs. not going overboard and working out three times a day.
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