Resources for understanding hypothalamic amenorrhea versus lean PCOS

When your period is missing, there is a standard workup doctors will do to try and determine the cause. They should do a physical exam, take a history and probably do some bloodwork. It is also fairly common to have a pelvic ultrasound.

When a woman with a history suggesting hypothalamic amenorrhea goes for an ultrasound, I warn her that it is common to see many small follicles (also called “cysts”) on her ovaries. That can lead to a doctor calling the ovaries “polycystic” and suggesting polycystic ovarian syndrome (PCOS) as a diagnosis.  As we described in our earlier post about HA versus lean PCOS, absent periods and ovaries with a lot of follicles are not sufficient to diagnose PCOS, especially with a history that points more toward hypothalamic amenorrhea.

We put together an information sheet to summarize the differences between hypothalamic amenorrhea and PCOS to help you and your doctors determine which is the correct diagnosis for you. In addition, we’re making the sixth chapter of No Period. Now What? available for download. This chapter not only discusses diagnosing HA and PCOS but also what might happen if you have both HA and PCOS, as well as some ideas for PCOS treatment and long-term concerns if you do in fact have PCOS. Enter your email address to receive an email with a download link for both. Please feel free to share the files: for example with your doctors and other women with HA/lean PCOS.

DiagnosingPCOSvsHAhalfpage

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Hope this helps!!  Any questions, please comment on this post or use the contact form!

Nico

In case you’re interested, references for the information sheet are listed below.

Hypothalamic Amenorrhea versus PCOS Information Sheet References

Diagnosing PCOS:

  • Johnson TRB, et al. “Evidence-Based Methodology Workshop on Polycystic Ovary
    Syndrome.” Bethesda, Maryland: National Institutes of Health, 2012. http://prevention.nih.gov/workshops/2012/pcos/docs/FinalReport.pdf
  • Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group.
    “Revised 2003 Consensus on Diagnostic Criteria and Long-term Health Risks Related
    to Polycystic Ovary Syndrome (PCOS).” Human Reproduction. 19(1) 2004: 41-47. doi:
    10.1093/humrep/deh098

Diagnosing polycystic ovaries:

  • Balen AH, et al. “Ultrasound Assessment of the Polycystic Ovary: International
    Consensus Definitions.” Human Reproduction Update. 9(6) 2003: 505-14. doi: 10.1093/
    humupd/dmg044
  • Dewailly D, et al. “Definition and Significance of Polycystic Ovarian Morphology:
    A Task Force Report from the Androgen Excess and Polycystic Ovary Syndrome Society.”
    Human Reproduction Update. 20(3) 2014: 334-52. doi: 10.1093/humupd/dmt061
  • Lujan ME, et al. “Updated Ultrasound Criteria for Polycystic Ovary Syndrome:
    Reliable Thresholds for Elevated Follicle Population and Ovarian Volume.” Human
    Reproduction. 28(5) 2013: 1361-368. doi: 10.1093/humrep/det062

Hyperandrogenism:

  • Liang SJ, et al. “Clinical and Biochemical Presentation of Polycystic Ovary Sydrome
    in Women between the Ages of 20 and 40.” Human Reproduction. 26(12) 2011: 3443-
    449. doi: 10.1093/humrep/der302
  • Azziz R, et al. “The Prevalence and Features of the Polycystic Ovary Syndrome in
    an Unselected Population.” The Journal of Clinical Endocrinology & Metabolism. 89(6)
    2004: 2745-749. doi: 10.1210/jc.2003-032046
  • Azziz R, et al. “Criteria for Defining Polycystic Ovary Syndrome as a Predominantly
    Hyperandrogenic Syndrome: An Androgen Excess Society Guideline.” The Journal of
    Clinical Endocrinology & Metabolism. 91(11) 2006: 4237-245. doi: 10.1210/jc.2006-0178
  • Sivayoganathan D, et al. “Full Investigation of Patients with Polycystic Ovary Syndrome
    (PCOS) Presenting to Four Different Clinical Specialties Reveals Significant
    Differences and Undiagnosed Morbidity.” Human Fertility. 14(4) 2011: 261-65. doi:
    10.3109/14647273.2011.632058
  • Ferriman D, Gallwey JD. “Clinical Assessment Of Body Hair Growth In Women.”
    The Journal of Clinical Endocrinology & Metabolism. 21(11) 1961: 1440-447. doi: 10.1210/jcem-21-11-1440
  • Kar, S. “Anthropometric, Clinical, and Metabolic Comparisons of the Four Rotterdam
    PCOS Phenotypes: A Prospective Study of PCOS Women.” Journal of Human
    Reproductive Sciences. 6(3) 2013: 194. doi: 10.4103/0974-1208.121422
  • Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group.
    2004. doi: 10.1093/humrep/deh098

Multi-cystic ovaries in women with hypothalamic amenorrhea:

  • Robin G, et al. “Polycystic Ovary-Like Abnormalities (PCO-L) in Women with
    Functional Hypothalamic Amenorrhea.” The Journal of Clinical Endocrinology & Metabolism.
    97(11) 2012: 4236-243. doi: 10.1210/jc.2012-1836
  • Falsetti, L. “Long-term Follow-up of Functional Hypothalamic Amenorrhea and
    Prognostic Factors.” The Journal of Clinical Endocrinology & Metabolism. 87(2) 2002):
    500-05. doi: 10.1210/jcem.87.2.8195

Resources for Understanding Hypothalamic Amenorrhea

There are common misconceptions about how hypothalamic amenorrhea / missing periods can arise. “Everyone” seems to know that women who have eating disorders or are Olympic-level athletes commonly lose their periods. What is much less well-known, however, is that women can lose their periods at much less extreme levels of calorie/food group restriction and exercise.

A big part of our book, No Period. Now What? is the survey of over 300 women that we completed, asking a variety of questions about factors leading to hypothalamic amenorrhea, steps taken to recover, and recovery success (as well as trying to get pregnant, pregnancy, and beyond.) From that survey we were able to get a much better picture of the range of women affected by hypothalamic amenorrhea.

Our last few posts have discussed the factors involved in acquiring HA: exercise and undereating, weight/weight loss, stress, and genetics, and also about how women who are not avid exercisers or “underweight” can have HA. But those posts can take a while to read through. So we put together an information sheet to help educate those experiencing missing periods / hypothalamic amenorrhea, as well as any others who might be interested (e.g. doctors, family members). In addition, we’re making the first chapter of our book, which describes the basics of hypothalamic amenorrhea, available for download. Enter your email address to receive an email with a download link for both. Please feel free to share the files: for example with your doctors, other women with HA, and friends or family members who might not understand why your periods are missing.

WhatIsHypothalamicAmenorrheaFirstHalf

Name:
Email:

Update: I recently put together a video explaining these five factors, in case you prefer visual learning.

Hope this helps!!  Any questions, please comment on this post or use the contact form!

Nico

In case you’re interested, references for the information sheet are listed below.

Understanding Hypothalamic Amenorrhea Information Sheet References

Causes of amenorrhea:

Effects of underfueling:

  • Wade GN, Jones JE. “Neuroendocrinology of Nutritional Infertility.” American
    Journal of Physiology: Regulatory, Integrative and Comparative Physiology. 287(6) 2004:
    R1277-1296. doi: 10.1152/ajpregu.00475.2004
  • “Balancing Calories to Manage Weight.” In Dietary Guidlines for Americans, 2010.
    7th Edition ed. Washington, D.C.: U.S. Department of Agriculture and U.S. Department
    of Health and Human Services, 2010. http://www.fns.usda.gov/sites/default/files/Chapter2.pdf

Exercise (stress) and hypothalamic amenorrhea:

  • Hill EE, et al. “Exercise and Circulating Cortisol Levels: The Intensity Threshold
    Effect.” Journal of Endocrinological Investigation. 31(7) 2008: 587-91. doi: 10.1007/BF03345606
  • Loucks AB, et al. “Alterations in the Hypothalamic-Pituitary-Ovarian and the
    Hypothalamic-Pituitary-Adrenal Axes in Athletic Women.” The Journal of Clinical
    Endocrinology & Metabolism. 68(2) 1989: 402-11. doi: 10.1210/jcem-68-2-402
  • Mastorakos GM, et al. “Exercise and the Stress System.” Hormones. 4(2) 2005:
    73-89. http://www.hormones.gr/57/article/article.html

Stress and hypothalamic amenorrhea:

  • Berga SL, et al. “Recovery of Ovarian Activity in Women with Functional
    Hypothalamic Amenorrhea Who Were Treated with Cognitive Behavior Therapy.”
    Fertility and Sterility. 80(4) 2003: 976-81. doi: 10.1016/S0015-0282(03)01124-5
  • Biller MK, et al. “Abnomal Cortisol Secretion and Responses to Corticotropin-
    Releasing Hormone in Women with Hypothalamic Amenorrhea.” Journal of
    Clinical Endocrinology & Metabolism. 70(2) 1990: 311-17. doi: 10.1210/jcem-70-2-311
  • Brundu B. “Increased Cortisol in the Cerebrospinal Fluid of Women with Functional
    Hypothalamic Amenorrhea.” Journal of Clinical Endocrinology & Metabolism.
    91(4) 2006: 1561-565. doi: 10.1210/jc.2005-2422

Genetics:

  • Caronia LM, et al. “A Genetic Basis for Functional Hypothalamic Amenorrhea.”
    The New England Journal of Medicine. 364(3) 2011: 215-25. doi: 10.1056/
    NEJMoa0911064
  • Gianetti E, et al. “When genetic load does not correlate with phenotypic spectrum: lessons from the GnRH receptor (GNRHR).” Journal of Clinical Endocrinology & Metabolism. 97(9) 2012: E1798-807. doi: 10.1210/jc.2012-1264

Factors in hypothalamic amenorrhea, Part 2

Last time we talked about the first two factors in missing periods / hypothalamic amenorrhea. Today we’ll talk about the remaining three: weight and weight loss, stress, and genetics. In a way you can think of these factors as spokes in a wheel. One broken spoke (one factor taken to extreme) could make a wheel non-functional. Or, multiple cracked but not yet broken spokes (multiple factors in play but none to an extreme) could end up having the same effect of a non-working wheel.

3. Weight and weight loss

It is common to think of hypothalamic amenorrhea / missing periods as an issue for women who are super-skinny, but as we described earlier, it is very possible to have HA at a higher weight. However, that said, a BMI under about 21-22 is for many women hard to maintain without some level of food restriction, and particularly at a BMI under 20 it is likely that weight and bodyfat are not high enough to support a functional reproductive system. This is particularly true in combination with other factors.

Here’s a graph that shows the BMI of our survey respondents when they were diagnosed with hypothalamic amenorrhea.Range of BMI when women had hypothalamic amenorrhea
The median BMI when HA was diagnosed was 19.0, 33% were “underweight” with a BMI of 18.5 or less, and 7.5% had a BMI of 22 or more.

The next part to this particular issue is weight loss. We were totally surprised when we analyzed our data to find that 82% of our survey respondents had lost more than 10 pounds at some point in the past. Weight loss and the caloric restriction that lead to that loss certainly played a part in my missing periods. Here’s the graph of that weight loss (each line represents 10% of the 272 women who provided these data):
Weight loss and hypothalamic amenorrhea
You can see that there was significant weight loss even in women whose starting weight/BMI was “normal”. I was certainly in that category. I thought I was being so healthy by losing weight in preparation for a healthy pregnancy – I didn’t take into account that the recommendations to try and lose weight in order to increase chances of pregnancy are meant for women who are overweight or obese. I really thought I was doing everything right. It took me a long time to come around to the fact that my body didn’t agree with my mind that I needed to be thinner.

4. Stress

Thee next factor is stress, and by that we really mean psychological stress. Exercise can also be seen as a form of stress by our brains but for now let’s examine the effects of purely mental stress. I’m sure you’ve heard stories of women skipping a period after the death of a loved one, or while going through a divorce. So mental stress alone can mess up a normal cycle.

I experienced the effects on my cycle of mental stress when my youngest was almost two. His leg broke while going down a slide with his father – they went over a bump and Cam’s leg got caught underneath Dad. (Side note, never ever do this, it is actually a common source of toddler injury). With two older children and a toddler with 2-year-old desires but now the physical abilities of a newborn, it was an incredibly stressful time for me. I was tracking my cycles and found that the stress manifested in a luteal phase (the time between ovulation and getting a period) that was about five days shorter than had been my norm. I imagine that had the stress continued for longer my cycle might have stopped altogether, but fortunately Cam started walking again three weeks after his cast came off.

So those are some of the effects of acute stress. But what about chronic stress? Perhaps from a family situation, maybe from work, or sometimes, just the stress of constantly trying to live up to the high ideals and goals we set for ourselves.  And the real kicker is that often those stress-inducing goals include maintaining a strict, “healthy” way of eating, and a daily or weekly exercise plan. Another irony is that worrying constantly about not getting a period can be felt by the body in exactly the same way, as chronic stress.

When you mix this stress together with caloric or food group restriction, you are even more likely to get HA. A study in monkeys found that stress alone (of moving to a different cage) disrupted menstrual cycles in a couple of sensitive monkeys. But when food restriction and exercise was layered on top of the stress, the mixture caused absent cycles in a large majority (but not all – those “lucky*” women who can be thin, run marathons, and get pregnant at the drop of a hat.)

5. Genetics

The last piece of the puzzle in getting to hypothalamic amenorrhea is likely to lie in our genes. A few recent studies have found mutations (small changes) in women with HA in the proteins along the pathways that are involved in control of the menstrual cycle. This suggests that some women have a greater predisposition to loss of periods than others.

This might feel unfair, but I have come to thank my lucky stars for having been so predisposed; missing my period gave me the challenge and reasons to change my ways which I thought were healthy but now realize had crossed the line of health and were creeping into obsessive territory.

I have found upon recovery, as have many, many others, that I do not need to be nearly as strict with myself in order to maintain a healthy weight. I have found a place where my exercise is in balance with the rest of my life and I am no longer compelled to work out every.single.day.

I am fairly sure that my hypothalamic amenorrhea came from genetics (I have a naturally short luteal phase which given the interconnectedness of all the hormones involved with our menstrual cycles leads me to believe that I am likely to have some mutations), severe caloric restriction leading to rapid weight loss, a low-for-me BMI of 19, and low bodyfat (16%) , along with overexercising. I kinda went gangbusters and just broke all my spokes at the same time – it’s no wonder my wheel was broken.

What’s your combination?

Factors in hypothalamic amenorrhea, Part 1

As far as we are concerned, there are five factors that play into whether a woman acquires hypothalamic amenorrhea (stops ovulating and has no period). The most common combination is undereating/underfueling, and overexercising/overtraining. But… that is far from the only way to get HA. Stress alone can cause one to miss a period; add in a little bit of food restriction or increase in exercise, and that one missed period turns into many. Or perhaps you were overweight at one point and lost more than 10 lb to get to a “normal” weight… that alone can cause missing periods, but add that weight loss to food group restriction, like a low-carb or low-fat diet, and boom. No periods.

Let’s go through the factors one by one, and I’ll share some more data from our survey respondents with you.

1. Exercise

The first factor we’ll consider is exercise.  I shared last week that the amount of exercise can vary widely among women with HA, although we do tend to exercise more than four days a week and for an hour or more at a time. What’s interesting, though, is when you look at exercise intensity. That is another part of the equation. We asked our survey respondents about the intensity of their exercise when their periods were missing versus prior to that, when periods were normal.

Average exercise intensity when women experience hypothalamic amenorrhea versus prior

The two lines show exercise intensity on a scale where 0 is sitting, 5 is moderate exercise like a fast walk or slow jog, heartrate in the 140-149 range; 10 is a personal record pace, heartrate 190+. Each point shows the percentage of 278 women who described the average intensity of exercise they performed prior to having hypothalamic amenorrhea compared with the average intensity when their periods were missing. You can clearly see a shift to the right, denoting higher exercise intensity when periods disappeared. With normal periods, the average intensity was between 4-6; when periods were absent, average intensity was more like 6-8.

2. Eating

The second factor is eating. In my case, I started limiting myself to 1500 calories a day, because that’s what my (male) coworkers were doing in an attempt to lose weight. I thought, hey, that should work for me, as a woman I need fewer calories than my guy friends, but I exercise more, so sure, let’s go with 1500.  I made myself an Excel file in which I tracked every morsel that passed my lips, and if I didn’t know the exact number of calories I would overestimate so I didn’t “eat too much.”

Not all our survey respondents tracked how many calories they were eating, but among those who did, my experience was fairly typical. The average consumption when our survey respondents had hypothalamic amenorrhea was 1481 calories a day.

Number of calories eaten per day for women with hypothalamic amenorrhea

This is something that many doctors don’t even ask about when a woman is missing her period. They look at the woman and her physique/BMI, and if she “looks” normal, they don’t dig any further. But many of us are severely restricting the amount of food we eat, mostly in order to maintain/attain the societal idea of thinness.  Never mind the cost.

If we’re not restricting the amount of food, there is often a feeling of wanting to avoid “unhealthy” food, whatever that might mean to you. For some it’s fat, for some carbs, for some cooked food… regardless, the mindset that you have to watch what you eat can cause inadvertent calorie restriction, and also mental stress (see tomorrow’s post!)

Were you exercising more or more intensely when you had hypothalamic amenorrhea than before or afterwards? Did you track and restrict calories, or avoid certain food groups?

I’ll finish this post up tomorrow, I need to get to bed!

-Nico

P.S. Feel free to download and share any of the graphs from these posts!

Hypothalamic amenorrhea if you’re not “fit” or “thin”?

Some women (like me) read a general description of hypothalamic amenorrhea as being caused by undereating and overexercising, and immediately know that’s their issue. In my case, I was exercising a minimum of two hours a day. I loved my sports, and played ice hockey 3-4 times a week, volleyball 1-2 times, biked to work a couple days a week (15 miles round trip), lifted weights 2-3 times a week, played squash with my coworkers, and golf (no cart for me!) on the weekends. And then I decided that I should lose some weight to have a healthy pregnancy and severely limited my calories (dropping me from a BMI of 22 to 19.5). Whoops, instant HA!

Others, though, it’s not nearly as clear cut. In a woman who’s only exercising 3-4 days a week, or whose BMI is 22, 23, over 25… doctors and other health professionals will often say, “Oh, your weight and exercise are fine.” The thing is, though, that when a woman has hypothalamic amenorrhea, both exercise and weight (as a symptom of calorie restriction) can be associated. Or perhaps not, and other factors are at play. Continue reading

Hypothalamic amenorrhea or lean PCOS???

When you’re not getting your period and trying to figure out why, it is important to determine whether you have hypothalamic amenorrhea or PCOS (polycystic ovarian syndrome, sometimes called “lean PCOS” in a woman with a BMI < 25), and the two are often confused.

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

Continue reading