Is PCOS hereditary? Could AMH be the true "cause" of PCOS?


Is PCOS Hereditary?

You’ve probably seen headlines saying “Cause of polycystic ovary syndrome discovered at last”

Well, is it really true? I dug in to the research to find out how this changes our knowledge of PCOS and how it relates to you, if you are a woman with PCOS currently trying to conceive.

Studying PCOS Heredity: Does AMH in pregnant women impact PCOS in offspring?

First we’ll do a quick overview of the hormones discussed in the study, then we’ll review how the study was conducted and the results they found, and finally we’ll talk about what this means for you as a woman with PCOS and what it means for you future daughters and granddaughters.

There was a study published in November 2018 that hypothesized that high AMH in pregnant women could be a cause of PCOS in the next generation.

The study centers around the Anti-Mullerian Hormone. The key function of this hormone is that it is responsible for making sure female embryos have a female reproductive system and male embryos have a male reproductive system.

But most of you know AMH because it’s also used as a way to measure ovarian reserve, or how many eggs you have left. Typically, low AMH indicates low ovarian reserve. However, women with PCOS have 2-3 times as much AMH as other women and typically the higher the AMH the more severe their PCOS is.

During pregnancy AMH levels are usually low. However this study was the first to actually measure AMH in pregnant women with PCOS. And they found that AMH was higher in pregnant women with PCOS than in other women. What’s even more interesting is that they divided the two groups by weight and found that Lean PCOS women had the highest AMH levels, while obese PCOS women actually had normal AMH levels.

So that is as far as the human portion of this study went. What we know for sure in humans is that lean PCOS women have higher AMH levels than usual.

From there, the researchers made a hypothesis, they wondered whether these high AMH levels might actually impact the chance of the offspring inheriting PCOS.

Studying PCOS Heredity: Testing high AMH in mice

So what they did next is gather a group of pregnant mice and inject them with AMH to mimic the high AMH in lean PCOS pregnant women.

They then watched to see how this changed the mice’s offspring.

Essentially what the study found is that the offspring of the high AMH mice did have all the classic signs of PCOS.

  • Delayed puberty onset

  • Disrupted cycle with anovulation

  • Fewer egg follicles and fewer corpus luteum developed than in control mice

  • Took them longer to have their first litter, and had fewer pups than control.

  • Higher testosterone and LH levels - common in humans with PCOS.

  • Decreased estrogen and progesterone production

  • No difference in body weight to control mice - further indicating that this discovery is more relevant to lean PCOS.

Remember this is in mice, we haven’t yet seen this in humans, but it’s a clear sign that further research is needed in humans.

Studying PCOS Heredity: Biochemical mechanisms

What this shows is that high AMH does have the potential to trigger a cascade of events that induce lean PCOS.

How does that work? What is the mechanism behind that? Well, there are two ways.

The first way is by diminishing the placenta’s ability to convert testosterone into estrogen. Remember from the beginning, the main responsibility of AMH during pregnancy is to differentiate the fetus between male and female. Male babies need high AMH in order to develop properly. So it looks like high AMH during development of a female baby impacts the placenta’s ability to convert testosterone into estrogen, possibly giving them a predisposition toward their own bodies having a disrupted testosterone to estrogen conversion down the line.

The second way AMH could contribute to PCOS in offspring is by affecting parts of the brain that regulate our hormones. We know that AMH does stimulate the hypothalamus, a part of your brain that regulates your hormonal system. If AMH is too high, the hypothalamus increases production of GnRH.

GnRH tell the pituitary, another part of your brain, to produce LH and FSH. High LH and FSH are typical in women with PCOS. FSH is responsible for recruiting eggs and helping them mature for ovulation. LH is what stimulates ovulation to happen. When these two hormones are too high, your cycle doesn’t work as it should. Too many eggs start maturing but none of them ever become dominant. AMH is produced inside developing follicles and so this is likely why women with PCOS have higher than usual AMH in the first place. And you can end up not ovulating at all that cycle.

We know that the high AMH and subsequent PCOS are directly linked to the function of the hypothalamus and pituitary.

In another group of mice the researchers did the same experiment except they gave them GnRH antagonist along with the AMH. GnRH is secreted by the hypothalamus and it tells the pituitary to release LH and FSH. When the researchers gave a substance that inhibits GnRH, along with AMH, none of the offspring had any signs of PCOS. They were on par with the control mice.

So what do we know so far?

  • We know that AMH is high in lean PCOS pregnant women, not in obese PCOS pregnant women.

  • We know that in mice, high AMH leads directly to offspring with PCOS.

  • We know that inhibiting production of GnRH reverses PCOS.

  • We know that GnRH is stimulated by high AMH, and also high estrogen during a normal cycle.

  • We know that GnRH is inhibited by low estrogen and by high progesterone.

So what does this mean for you?

Well a lot of the headlines talking about this article said the cause of PCOS discovered at last. I don’t think that’s true. For one, the results are only relevant for the lean PCOS type, which is the minority of PCOS cases.

We also need further research to see if these results are as cut and dry in humans. And since it takes much longer for humans to mature, we won’t know if the children of the women with high AMH will show signs of PCOS or not.

PCOS is a complicated condition. Everything in our environment, our food, our water, the make up you wear, how much sleep you get, as a huge potential to impact your hormones and the severity of your PCOS.

I also think that, learning more about the genetic side of hormones is important for science, but it doesn't serve you to think the your PCOS is genetic. It takes all of the power out of your hands and gives the impression that there’s nothing you can do about it. It puts PCOS in the same bucket as your hair color or your height. Those are genetic attributes that you can’t change. But, thousands and thousands of women have been able to reverse their PCOS. We know that you do have power to improve your hormones.

Whenever I look at studies I’m always trying to see how this information is helpful clinically, how is this going to help me help my clients.

The key piece that I took out of this study is the reminder of how important our hormonal feedback loops are for maintaining balance. Our pituitary and hypothalamus are constantly monitoring what hormones are in our blood, at what quantities, for how long. They are the master hormone regulators of the body. In this video we talked about how AMH stimulates the hypothalamus. But that’s not the only factor that influences your hypothalamus. Your hunger hormones, leptin and ghrelin impact your hypothalamus, your stress levels impact your hypothalamus.

Everything in our hormonal system is deeply intertwined. Changing one part has a domino affect that changes all of the other hormones too. And that’s a really good thing to know when you have a hormonal imbalance like PCOS. It means that you just have to start tipping over dominoes, one at a time, and you’ll see a whole cascade of changes. This is how PCOS gets reversed. One change at a time.

Mollie Williams