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PCOS: Causes, Genetics, and Natural Solutions

Key takeaways:
~ PCOS – polycystic ovary syndrome – is a systemic disorder that can cause symptoms of menstrual irregularities, altered hormone levels, weight gain, and ovarian cysts.
~ Multiple pathways can cause PCOS, including metabolic causes, hormonal dysregulation, or circadian rhythm-driven changes.
~ Understanding your genetic susceptibility may help you to target the right underlying cause.

Members will see their genotype report below, plus additional solutions in the Lifehacks section. Join today 

Getting to the root cause of PCOS:

Polycystic ovary syndrome (PCOS) is an endocrine disorder that causes an increase in androgen hormone production in women. It affects 5 -10% of premenopausal women. Genetics plays a large role in whether you have PCOS.

No single 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.

Symptoms of PCOS:

PCOS symptoms include:[ref]

  • Irregular menstrual cycles
  • High androgen hormones, sometimes leading to facial hair
  • Possible presence of  cysts in the ovaries
  • Weight gain
  • Insulin resistance
  • Elevated luteinizing hormone (LH) levels.

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]

Deep dive into the causes of PCOS:

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:

  1. Hormone dysregulation
  2. Insulin resistance and hyperinsulinemia
  3. Circadian rhythm changes

1) 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 a new follicle (containing an egg) in the ovary. The follicle produces estrogen, causing estrogen to rise over the next week.

Around days 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.

Reproductive phenotype:
For some women, the hormonal changes are driving PCOS.[ref]

2) Insulin resistance and androgen hormone production:

Women with PCOS often have problems with insulin resistance and higher blood glucose levels. These metabolic changes can a driving factor in the hormonal changes seen in PCOS. [ref]

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]

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.

Mendelian randomization studies can help to understand whether a genetic pathway is causal for a condition. In PCOS, there is a strong genetic link between BCAA (branched-chain amino acid) levels, insulin resistance, and the cause of PCOS.[ref]

Related article: Insulin resistance, BCAAs, and Genetics

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:

Recent studies have unveiled a significant link between disruptions in circadian rhythm and the development of Polycystic Ovary Syndrome (PCOS).[ref]

A Brief Overview of Circadian Rhythm:
Circadian rhythm, commonly referred to as your body’s internal clock, orchestrates a 24-hour cycle of biological processes. It’s widely recognized for regulating the sleep-wake cycle, but its influence extends far beyond sleep, impacting various metabolic and cellular functions. This rhythm, dictated largely by light exposure, ensures that certain bodily processes occur optimally during the day or night.

Circadian Rhythm Disruption: A Modern Health Challenge:
The disturbance of this natural rhythm has been linked to several chronic conditions, such as obesity, heart disease, and dementia. Imagine the disorientation of jet lag; this analogy helps us grasp how circadian rhythm disruption can leave our bodies feeling out of sync. Everyday examples include staying up late under bright lights, leading to what is termed ‘social jet lag.’

The body’s circadian clock is driving the rise and fall 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.

Circadian Rhythm’s Role in PCOS:
Researchers, through animal studies, have found that disrupting circadian rhythm can cause the same alterations to hormones as are seen in PCOS. For decades it was known that altering circadian rhythm could alter insulin sensitivity and androgen production. The latest research, however, goes a step further. By manipulating light exposure, scientists demonstrated that changes in circadian clock genes could directly influence the hormonal imbalances seen in PCOS.

The researchers used changes in light to show that alterations to the circadian clock genes caused the downstream effects on the hormones involved in PCOS.[ref]

These findings suggest that lifestyle adjustments, particularly in managing light exposure, could play a crucial role in addressing PCOS, offering new perspectives in both understanding and managing this syndrome.

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?

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]

There’s quite a bit of research on ways to reverse PCOS. 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.[ref]

With the strong link to insulin resistance, aligning your diet to decrease IR may give you the best results in the long run.

Related article: Insulin Resistance and Genetics: Finding the Root Cause

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


Genetics and PCOS:

Genetics play a significant role in PCOS. Studies suggest that about 70% of PCOS cases have a hereditary component, indicating a strong genetic influence in its development.

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.

PCOS Genotype Report

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Lifehacks

If you are under a doctor’s care, be sure to talk with your doctor before making any changes to supplements or diet.

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 the combination of all 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 and the Resolution of Inflammation:

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Updated May 15, 2020


About the Author:
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 from Colorado School of Mines and 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.