There has been some really interesting research on PCOS and hypothalamic amenorrhea that has come out in the two years since No Period. Now What? (NPNW) was published. I’ll start with a review of the recent literature, then break it down more in a few subsequent posts and videos to come.
As a reminder, Poly Cystic Ovarian Syndrome (PCOS) is a condition typically associated with high androgen levels (“male” hormones although it’s totally normal for women to have them too), although the criteria for diagnosis are such that women with hypothalamic amenorrhea (HA) are often misdiagnosed with PCOS. You can read more in Chapter 6 of NPNW, which you can download for free.
My first comment is that there have been a number of research studies that support the conclusions drawn in NPNW. For example this study from 2015 that finds using the old criteria for “polycystic ovaries” of > 12 follicles on one ovary, many women are misdiagnosed with PCOS. In this study of correlations between high AMH and PCOS (covered in more detail below) the authors likewise find that in 86% of women in smaller bodies, PCOS is misdiagnosed if HA is not first ruled out, as it should be (they used a low BMI cutoff, but I find the same is true across a much larger range of body sizes).
As you will read in the PCOS vs. HA chapter in NPNW, the reason the correct diagnosis is important is that the lifestyle changes recommended to address each condition are essentially opposite. In order to recover from HA, one typically needs to eat more (amount and food types) and exercise less (particularly cutting out high intensity exercise), whereas the recommendations made to lessen the symptoms of PCOS are often to reduce food intake, cut out specific food groups, and exercise more. (Whether those recommendations are accurate for treatment of PCOS is not something I have looked into in great detail, but that is what women are commonly told to do by their physicians.) If you follow those PCOS recommendations when in fact you have HA, all you are doing is digging yourself further into the hormonal hole you’re already in. So. Correct diagnosis is really important, and if any of the factors below apply to you, particularly if more than one does, chances are that you have HA and not PCOS. See the info sheet and book chapter for more clarity.
1. Low BMI and/or weight loss of more than 10 lb 2. Stress fracture or low bone density measured by DXA 3. Restrictive eating habits, either amount or variety. 4. Regular (often excessive but not always) exercise 5. Chronic or acute stress, or perfectionism
The relationship between AMH, PCOS, and HA
The second topic I wanted to cover is that in recent years, Anti-Mullerian Hormone (AMH) has been used more frequently to assess both diminished ovarian reserve and as a marker for PCOS (high levels of AMH). Low AMH and diminished ovarian reserve is discussed in NPNW on pages 271-274… it seems that in women with HA, low AMH is not uncommon and doesn’t really have anything to do with ovarian reserve. That’s a post for another time though.
Today, I want to talk about the opposite issue – high AMH. In my observations, women with no period due to HA often have elevated AMH along with a large number of small resting follicles, but do not manifest any other signs of PCOS (like increased androgens in blood or physical manifestations of increased androgens).
This study looked at 141 women of varied body sizes, all with elevated AMH. They found NO elevated androgens or physical signs of hyperandrogenism in women in smaller bodies who fit an HA profile with at least one of the following: eating disorder, exercise >=5 days per week, preoccupation with weight, or reliance on calories counting. There was a strong correlation between high AMH and “polycystic ovaries”, but this clearly did not mean PCOS. (Unfortunately the researchers did not share exactly what criteria they used to define “polycystic ovaries.”) Even in the women in smaller bodies without HA lifestyle tendencies, high AMH was generally not indicative of of hyperandrogenism. This is really important to know, because women are often told that high AMH means they have PCOS. As we keep highlighting, this is not true; HA MUST be ruled out first before an appropriate diagnosis of PCOS can be made.
One other very interesting and novel finding from this study is that the sex hormone binding globulin (SHBG) was significantly higher in women with HA than those without. The authors suggest this is worthy of further study as a possible marker for HA. There really isn’t anything else out there at the moment that we can use to diagnose HA; LH tends to be low or low/normal in women with HA, but there is a significant percentage (about 30%) for whom LH is right in the middle of the normal range.
In a study that followed women with HA who recovered menstrual cycles for a year, another group found that PCOS-like tendencies manifesting around the time of recovery, such as high AMH, multicystic ovaries, testosterone (T), and DHEAS, normalized in the year following recovery.
In the study, 28 women with HA were examined and divided into two groups based on AMH levels; “normal” with AMH < 4.7 ng/mL (16 women) or “elevated” AMH > 4.7 ng/mL (12 women). Those who had elevated AMH had higher testosterone levels (although still in the normal range for females), and also larger ovaries. In all cases except one, these values were lowered after a year in recovery, as seen in the table below. The one exception seemed to develop bona fide PCOS (ovarian volume of 10.8 cc, 25 follicles in her ovary, T of 78 ng/dL, and continued high AMH at 8.5 ng/mL).
High LH after HA recovery?
I have seen quite a few women with elevations in LH during or after recovery, to about twice their FSH level. An elevated LH to FSH ratio is sometimes seen in women with PCOS, but it is not diagnostic, meaning that there can be other explanations. One explanation is an LH surge that will trigger ovulation – this would normally be associated with high estradiol levels, around 200 ng/mL for a single dominant follicle.
In the cases I have seen, the high LH does not seem to be associated with ovulation because estradiol levels are still at baseline but nor does it seem to point to PCOS as there are not related elevations in androgens or increases in ovary size or follicle number. Research suggests that elevated LH is due to increased GnRH (gonadotropin releasing hormone) pulses, whereas slower GnRH pulses lead to low LH as is typically seen with HA. My suspicion is that in women a small subset of women who have or had HA, as the factors shutting down their hypothalamus are removed, the hypothalamus goes a little too far in the other direction, speeding up pulses more than is necessary. This leads to an increased LH level for a time.
Summary
The importance of a thorough patient evaluation in diagnosing the underlying cause of amenorrhea / no periods cannot be stressed enough. The different possible diagnoses have very different treatment recommendations, so getting diagnosis right is key. And in the comparison between PCOS and HA, it is clear that HA must first be ruled out.
PCOS can not be diagnosed by any of the following:
Amenorrhea + Polycystic or polycystic appearing ovaries, without excluding hypothalamic amenorrhea first
High AMH
High LH (even if 2-3x FSH)
Have you been diagnosed with PCOS? Based on what? Do you think that HA might be a possibility?
<3
Nico
P.S. If you’d like to work with me to figure out if you have HA, PCOS, or both, as well as come up with a recovery plan for YOU, schedule a call with me! And if you appreciated this post and would like to support more like it, please consider becoming a Patreon!
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