Tuesday, June 16, 2009

Hypothalamic Amenorrhea Recovery / Treatment Summary

I have been posting on the hypothalamic amenorrhea (HA) bulletin board over at fertilethoughts forums for almost three years now - I wished when I was diagnosed and starting treatment that there was someone who had already been there that I could talk to about what I was going through. It makes me warm and fuzzy inside to be able to provide that input and insight to others who are going through the same things now.

Over those three years, I've learned a lot, and also collected some pretty interesting stats that I thought I would share here for anyone who finds this blog searching for info on HA.

There seem to be two different flavors of HA, both with the same manifestations. The first variety comes in women who are normal to low weight, and undereat / overexercise to a BMI anywhere from 21 on down. The second happens in women who were overweight to begin with, then lost a significant amount of weight; in some cases going to low BMIs as well, but occasionally just to a 'normal' BMI of 23-25.

In the first case, gaining weight and cutting exercise seem, without fail, to restore natural cycles. This is despite what many doctors have told women on the board, "You could gain 50lbs and still not start cycling again." This is NOT TRUE. I'm finally starting to see posts from some women who say that their doctors won't treat them until they've gained some weight. The thing is, not only does gaining weight and cutting exercise help with complete recovery from HA, it also helps with treatment cycles if the natural approach isn't fitting in with timelines. There have been a number of women on the board who have either tried Clomid with no success, or injectibles with cancelled cycles for overstimulation, and even multiple failed IVFs. After weight gain, Clomid works in *many* cases despite the traditional wisdom in the literature that it won't work for HA because of the low estrogen. Injectible cycles go significantly better after weight gain. And IVF cycles seem to be much more successful as well. Also, the weight gain that comes with pregnancy is mentally much easier when some of the disordered eating / exercise / body image issues have been conquered prior to pregnancy.

In this first type of HA, what happens is that as the body goes into a semi starvation mode with a constant energy deficit due to the undereating/overexercising, leptin levels decrease (see Welt CK et al. for the full article). This then leads to decreases in the levels and pulsatile frequency of LH, and estradiol, and the natural hormonal cycle stops. Increases in eating, particularly in carbohydrates and fats (good and bad) restore the natural leptin levels within a reasonable amount of time - usually 6 months to a year after making wholehearted changes (in many cases cycles are restored even more quickly than that; the quicker the weight is gained, the more quickly the cycles return).

In the second type of HA, in women who were overweight and then lost a significant amount, it seems take much longer for cycles to return. I believe this is because in people who are overweight, leptin receptors become desensitized, and not as responsive to the leptin signals. When the weight loss occurs, leptin levels decrease, just as in the first variety. But when eating is resumed / overexercising moderated, the increase in leptin levels is not registered as quickly by the body because the leptin receptors are not as responsive. This is my own theory, but it's the only thing I've been able to come up with to explain why women who were overweight seem to have a less tractable form of HA.

So the upshot is, if you have HA having been normal weight / thin most of your life, you can restore your cycles reasonably easily by gaining weight to a BMI of around 23. For most women that has done the trick; many have resumed cycling at a lower BMI than that. It takes committment, it takes handling feeling "fat" (although as a whole we tend to have quite skewed body images - many of our significant others and friends comment on how much better we look after gaining weight - and they do mean it!), buying new clothes in larger sizes really helps. If you have HA and were overweight before losing / exercising, weight gain will still help with treatment, but it will likely take longer before your cycles will return naturally.

If you want to be pregnant NOW (and who doesn't after deciding it's time?), weight gain can still really help. As you can see by checking the stats below, Clomid DOES work in many women with HA after weight gain. Sometimes even without a positive response to Provera. If you have HA, and don't have insurance that covers injectibles, I think you should absolutely 100% give Clomid a try before putting down the cash for an injectibles cycle. If your OB or RE will go for it, the extended Clomid protocol seems to have great results; if not, even a standard Clomid protocol will often work.

Starting in October 2007 I kept track of (just about) all the women who posted on the HA board, how they got their BFP's (which almost everyone has, still working on some of the recent joiners) and other random information.

So far, there have been 82 BFP's in total. Unfortunately, 14 (17%) of those have resulted in miscarriage, which is fairly close to the rate that is normally quoted for miscarriage. Of those 82 pregnancies, the breakdown by method of conception is as follows:

Natural: 31 (38%)
Clomid (including extended protocol): 22 (27%)
Injectibles: 20 (24%)
IVF: 5 (6%)

Also, these stats do include some women second pregnancies after recover from HA. By and large, if weight loss post partum is moderated and the patterns of undereating/overexercising are not resumed, natural cycles are restored after weaning (it is extremely rare for a former sufferer of HA to resume cycles while nursing). Most of the subsequent pregnancies are falling into the natural category.

As you can see, this totally belies both the assertion of medical professionals that you can gain an infinite amount of weight and still not cycle again, as well as the idea that Clomid will not work. In fact, 70% of the pregnancies achieved (after 10/2007) on the HA board have been through one of those two methods. And I am firmly convinced that many of the women who did use injectibles or IVF could have gotten pregnant either naturally or with Clomid had timetables been different.

As this is my summary of all I've learned about HA over the past three plus years, a few other things that seem to come up frequently:

* As our cycles return, they tend to be quite a bit longer than normal cycles, with ovulation in the CD40's (or higher) for the first cycle not uncommon. As weight gain is maintained, cycles get shorter. This isn't a surprise, as it takes a while for the body to respond to the restored hormonal levels.
* A BFP on a late ovulation is not a problem at all, despite what you may read online. The thing is, that the follicle is not sitting around with a mature egg in it; once the follicular recruitment really takes off, ovulation is actually occurring in a normal timeframe; it just takes longer to get to the follicular recruitment phase.
* Speaking of which, it's not uncommon to go through 2-3 follicular recruitment waves accompanied by changes in cervical fluid / temp prior to actual ovulation occurring, especially as cycles are returning.
* Estradiol is NOT the be-all-end-all as far as HA diagnosis goes. In fact, estradiol levels don't really seem to correlate much with whether natural cycles will return or Clomid will work. For me personally, my e2 when I was not cycling was 32; the two cycles where I got pregnant it was 27 and 34 respectively. It seems that the LH number is much more indicative of HA status - LH below 2 is likely to indicate HA; as recovery continues, that number rises much more reliably than e2 does.
* If Clomid is used, we *still* tend to have longer than normal cycles, often not ovulating until somewhere between CD20-30, so that should be your expectation. Monitoring is a great idea if you can afford it / your doc will do it - there are cases where women have grown good sized follicles but just not been able to muster the LH support to surge properly to ovulate. If you're being monitored and this seems to be the case, a shot of Ovidrel can be given at relatively low expense, to induce ovulation.
* If you want to move on to treatment and have the option of using the GnRH pump or patch, jump on it! They seem to be far the best ways to induce follicle growth without overstimming.
* In injectible cycles, it is extremely easy to overstimulate as our bodies are not used to the hormones that are being injected. First, your injectible should absolutely include LH (so Menopur or Repronex) - the cycles that have been completed on the board with FSH alone (e.g. follistim, bravelle etc.) are generally much less successful. Second, your protocol on your first cycle should be to start with a single vial (75U, or even less) for at least 4-5 days. Increase the dosage after that, preferably by just a half vial at a time. I have seen too many cases where either a higher dosage (common in injectible cycles for non-HA women) or too quick/big jumps in dosage lead to multiple follicles and either cycle cancellation or multiple pregnancy. In most cases we tend to be quite fertile once ovulation is induced, so the goal on the first cycle should be one mature follicle, or at most two. Of those 82 pregnancies, 3 were triplet pregnancies (two from Clomid) and one was a quadruplet; prior to 10/2007 there were two other triplet pregnancies and another quadruplet on the board. *Many* of the women on the board who moved to injectible treatment were successful on the first cycle.
* Injectible cycles following the recommended low/slow protocol DO tend to be quite long, with stimming for two-three weeks not out of the ordinary. There's nothing wrong with this, and no reason for the cycle to be cancelled - you will find a dosage at which you respond, and your follicle(s) will take off from there. Generally once a follicle gets to be 12mm+ / e2 goes over 100, the stimming will just take a few more days until trigger.
* For subsequent cycles, if needed, you should NOT start with the dosage that you finally responded at; that will almost certainly lead to recruitment of too many follicles. Start at least half a vial lower than that for the first 4-5 days, then bump up to the dose you respond to.

If anyone comes across this post and has questions or comments, I'd be happy to respond, feel free to use the comments section.