PCOS and hypothalamic amenorrhea

What happens in PCOS: is PCOS more common or is it misdiagnosed?

Both: It happens that PCOS is over-diagnosed with ultrasound, in fact, detecting the presence of polycystic ovaries means essentially nothing, especially with the more modern ultrasounds where they are only high-resolution and simply see more follicles, which is normal in the young woman. Follicles in this case are mistaken for cysts, but ovarian cysts are something completely different. At the same time, there is probably also a problem of underdiagnosis, because there are many women who have an ovulatory cycle and insulin resistance and have not been told they have PCOS. A correct and useful first diagnostic approach of PCOS is to detect androgen excess when all other causes of androgen excess have been ruled out such as e.g., adrenal hyperplasia, hyperprolactinemia,..... and insulin resistance is the main driver of elevated androgens.

At the base we find a reshuffling of insulin and testosterone.

So certainly on the one hand insulin resistance in vulnerable women can increase androgens, and on the other hand having high androgens can worsen insulin resistance: perhaps testosterone is the primum movens.

And it appears that this already happens in fetal life: exposure to environmental toxins (xenoestrogens, pesticides, plasticizers) and epigenetics in utero: this can result in higher LH levels that stimulate more testosterone and potentially feed the two-way testosterone-insulin cycle in this way.

By now there is a wealth of research on exposure to toxins in utero, such as BPA, but also PCBs etc. and their consequences. Add to that the enormous impact on fertility of xenoestrogenic substances: the phenomenon of in vitro fertilization has also grown tremendously as a result of our lifestyle of the last 50, 60, 70 years.

In a nutshell in PCOS we have elevated androgen levels, so by definition to make a diagnosis of PCOS, androgens must be present and elevated, but often there are anovulatory cycles as part of it.

Restoring ovulation is one of the most important things to do in PCOS: both as an end in itself but also because both estradiol and progesterone have natural antiandrogenic effects: in fact, progesterone helps suppress LH so as not to overstimulate androgens in the ovaries. Useful is cyclic therapy with micronized oral progesterone, not a progestin, used for two consecutive weeks, followed by two weeks of rest. If there is no cycle, it can be started at any time, if not, from day 14 to day 26 of the cycle. Undoubtedly it is preferable after ovulation, if it can be confirmed that ovulation occurred following the temperatures. There are also women who clearly feel if they ovulate. We are interested in the main mechanism that is progesterone suppressing LH, which is chronically elevated in PCOS. And exactly by measuring LH and FSH you distinguish PCOS from hypothalamic amenorrhea. Women with PCOS had a higher LH to FSH ratio, and women with hypothalamic amenorrhea have a low LH to FSH ratio. Let's not forget that there is a lot of overlap between the two conditions as both can have irregular cycles or no cycle at all. Both PCOS and hypothalamic amenorrhea can have polycystic ovaries. Always clearly ask your patients if they are eating adequately! Detecting this anamnestic data can help you make a diagnosis of hypothalamic amenorrhea. An ovary with many cysts, also referred to as a polycystic or multicystic ovary, is just an ovary that does not have a dominant follicle and is not ovulating. Any woman, even a woman with perfectly normal hormones, who has mostly ovulatory cycles, may have an occasional anovulatory cycle. In a population of normal women with normal hormones, without PCOS, 1 in 4 will have polycystic ovaries at some point in their lives. Which really means nothing. Of course, the opposite is also true: not detecting polycystic ovaries cannot rule out PCOS because PCOS is an elevated androgen condition. And if they have signs of high androgens, it doesn't matter whether they have polycystic ovaries or not. The only other criterion is to rule out other causes. Be careful, of course, at what stage of the cycle you take the blood sample: ideally taking the sample on the second day of the cycle, if there is a cycle, is optimal. As the years go by, both FSH and LH tend to increase.

If the LH level is very low, which could be half that of FSH, plus a low fasting insulin level, plus a clinical history of some kind of dietary restriction, low BMI, the diagnosis is clear for hypothalamic amenorrhea. Here one has to increase the caloric intake for the months to come, and it will take at least 3-4 months for menstruation to return. And also, younger women are much more likely to miss their periods due to lack of food than older women. It just has to do with gynecological age. They are just more vulnerable, as if the hypothalamus does not want to take the risk of pregnancy under adverse conditions.

You may not know: the ovarian follicle begins its journey to ovulation 100 days before it actually reaches target. When you're trying to restore ovulation in hypothalamic amenorrhea, the time needed is always at least 100 days, counting that those follicles need to receive the correct pituitary signals, to be in a proper, noninflamed environment, to receive nourishment, antioxidants.

In PCOS in case of insulin resistance, the latter is the first to be treated. If the major problem, on the other hand, is very high androgen values, this is where our major therapeutic efforts will be focused. I would absolutely start with 3-6 grams of inositol, which works as an intracellular hormone signal amplifier of FSH and TSH. Great for both insulin resistance but also for other types of PCOS, precisely because of the property on FSH.

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