Hypothalamic amenorrhea or PCOS???

When you have no period and are trying to figure out why, it is important to determine whether you have hypothalamic amenorrhea or PCOS, and the two are often confused. (See this post for additional resources, including a free downloadable information sheet and the “HA/PCOS Conundrum” chapter of No Period. Now What?)

The World Health Organization has three classifications for infertility associated with anovulation and amenorrhea. Group I comprises those with low gonadotropins (luteinizing hormone (LH) and follicle stimulating hormone (FSH)) and estrogen, Group II consists of women with normal gondadotropins/estrogen, Group III is women with increased gonadotropins (e.g. in perimenopause).

In typical hypothalamic amenorrhea, which is essentially what the WHO Group I describes, LH is low, often less than 2 IU/L, as you can see in this figure showing LH levels in 45 women when they were diagnosed with hypothalamic amenorrhea. Note that the two women with LH values > 10 were further investigated for possible PCOS.

LH in women with hypothalamic amenorrhea

Sometimes an ultrasound of the ovaries will show multiple small follicles between 2 – 9 mm in size, this is common in women who are not ovulating. The observation will often lead doctors to calling the ovaries “polycystic” and diagnosing PCOS, however in these women with low gonadotropins, particularly low LH, a diagnosis of PCOS is very often incorrect. It is important to assess history:

  • Any history of significant weight loss (> 10 lb)?
  • Were periods regular in the past? How did exercise, weight, and eating habits then compare to now, with missing periods?
  • What is the woman’s current weight and bodyfat?
  • What are her eating habits? Is there restriction either of food amounts or varieties?
  • What are her exercise habits like?
  • What sources of stress are present? This can include acute stress such as death of a loved one, or chronic stress, which for many can derive simply from trying to live up to a perfectionist ideal.

In WHO Group II, with normal gonadotropin levels, it becomes harder to distinguish between HA and PCOS, particularly as the criteria for PCOS are easily met by a women with hypothalamic amenorrhea. In 2004 a group of doctors met in Rotterdam and came up with three components commonly seen in a woman with PCOS. These were:

  • Oligo or an-ovulation (infrequent or missing ovulation and periods)
  • Polycystic ovary morphology (ovaries containing multiple small follicles also known as “cysts”)
  • Hyperandrogenism (increased levels of “male” hormones measured through blood work or physical manifestations)

You will note that women with hypothalamic amenorrhea fit these same criteria. Missing periods? Check. Polycystic ovaries? Well… even if not technically meeting the definition of polycystic, as we mentioned it is common for a woman with hypothalamic amenorrhea to have multiple small cysts on her ovaries so many doctors will incorrectly call them polycystic, and boom, you’re told you have PCOS.

Jessica O: After a year of unsuccessfully trying to conceive (TTC), my doctor ran a bunch of tests and did an ultrasound. Everything was normal, except that the ultrasound showed ovarian cysts. So, they diagnosed me with PCOS and put me on metformin… I decided to get serious about treating my supposed PCOS, so I went on a low carb diet, lost some weight, and became obsessed with getting my daily workouts in. Surprise, surprise; at that point, I developed full-blown HA. My doctors continued to assume that my problems were caused by PCOS and no one knew why things were getting worse rather than better. It was an incredibly frustrating experience. I was never actually diagnosed with HA, but when I found Nico’s blog and the Board, it all started to make sense. I gained weight, cut back on exercise, and regained my cycle.

Over the intervening years a number of groups have examined what the threshold of “antral follicles” (those small baseline follicles I mentioned earlier, size of 2 – 9 mm) should be to more accurately diagnose PCOS. When the Rotterdam criteria were originally published, the cutoff for declaring an ovary polycystic was 12 antral follicles, or an ovarian volume greater than 10 cc. More recently, 20, or even 25 antral follicles per ovary has been suggested as a cutoff that will more accurately distinguish between a normal ovary and polycystic one.

A recent paper, and the impetus for this post, examined in-depth information about 75 women who had been diagnosed with “WHO type II anovulatory infertility.” Among these 75 women, 93% would be diagnosed with PCOS using the original criteria. However, for many, there is little additional evidence of PCOS.

If one requires more than 25 antral follicles in order to classify a woman as having PCOS, 39/75 of the Group II women would be included, 52% of the total. Among these women:

  • LH was significantly higher than those with fewer than 25 antral follicles (11.2 vs. 6.3 IU/L)
  • 41% had an LH/FSH ratio greater than 2, versus 11% of those with fewer than 25 antral follicles
  • 41% had indications of hyperandrogenism, either physical or biochemical, vs. 19%

Therefore, the cutoff of 25 antral follicles likely gives a more solid PCOS diagnosis than the lower numbers.

These differences between the two groups suggest two conclusions. First, that there are women who have normal gonadotropins who are less likely to have PCOS based on not exhibiting any other symptoms, and for these women, hypothalamic amenorrhea should be investigated as a cause of missing periods. Second, neither condition is cut and dried – there is a range of manifestations from severe to mild, which makes a 100% diagnosis tough to come by.

What we can tell you, though, is if you perform regular high intensity exercise, restrict what you eat (either in amount or variety), have lost a significant amount of weight in the past few years (typically 10+ pounds), or have experienced acute or ongoing stress (including the stress of being a perfectionist, which many of us are!) – it is very possible that a missing period is due to hypothalamic amenorrhea not PCOS. Try out the HA Recovery Plan we describe in our book and see what happens.

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