POF Diagnosis and Causes
Dr. Nanette Santoro's POF FAQ

1. What is the difference between primary and secondary amenorrhea?

It doesn't make much of a difference what your diagnosis is in terms of therapy, but the diagnosis of primary amenorrhea refers to the fact that you never had a period on your own. In your email you write that you never ovulated on your own, but did you have another diagnosis then like polycystic ovaries or something? In that case, your ovaries might have been making hormones, but they were being produced in such a way that you wouldn't get periods. That's the only way I would consider classifying you as 'secondary amenorrhea' otherwise I think you are right, that your amenorrhea is primary.

2. I really want to find out is why the POF has happened. Should I pursue going to an endocrinologist? If so, what tests should I expect to have done on me?

About a third of women with POF have no identifiable cause. The bulk of the scientific evidence about them indicates that they only have a problem with the ovaries. There are not problems with other endocrine systems. My advice to you is to see a Reproductive Endocrinologist with some expertise in this area. A Board-Certified Reproductive Endocrinologist is preferred. A Medical Endocrinologist with expertise is also reasonable.

Most women with POF have no clear explanation for their problem. In another third of women with POF, there are signs of 'autoimmune' processes that are going on, but it doesn't look like you have any clear cut autoimmune disorder. Maybe you will develop one at some point in time. You should be followed for signs of this sort of problem. POF appears to attack only the ovaries. There is no generalized aging of your whole body that goes along with this and you are not like a 50 year old menopausal woman because you have POF. However, it does bring up some special concerns for which you should be medically followed.

3. Where do I go from here?

Your best next move can be decided by a careful consultation with either a hormone specialist (Reproductive Endocrinologist or Endocrinologist) or a menopause specialist. It would depend upon where you live who would be the best doctor for you.

4. POF & the Thyroid - Are all these linked and if so, what could be the next thing I should look out for?

Thyroid problems are sometimes linked to POF in that they can be evidence of an autoimmune condition when they both exist together. You would need further testing to check this out, but I would advise you to discuss it with your doctor.

5. Can stress cause the POF or mimic it in some way?

There is no good evidence that POF is related to stress. Stress can cause a loss of periods but that is usually on a different basis than POF. Stress typically causes problems for the menstrual cycle by making too little FSH and LH get released from the pituitary. There is a very rare condition in which severe, life-threatening stress can cause a disorder like POF. The disorder is called 'Netter's Amernorrhea' named after a French physician who first described it in the 1950's. He found about 4 women with POF in whom it seemed to be related to very severe, life-threatening stress (like almost dying in an accident, that sort of stress!), but it's never been duplicated. It remains a medical curiosity. As far as I can tell, it has not been reported on since!

6. Do the hot flashes and other miserable symptoms ever end? How long do they usually last? Is it generally different for POF women?

The hot flashes usually decrease in intensity for many women, but for some they remain as unpleasant as ever. There are not known differences for POF women.

7. Are there any higher risks for POF women, (other than apparently heart and bones) - for instance, ovarian cancer? Should any special medical testing be done if one has had POF?

There are no clear cut reported increases in health risks for women with POF. There are some new studies being done that may help to clarify this in a couple of years. The only special medical testing that should be done for POF, in my opinion, is to test periodically for the autoimmune variety of POF -in other words, some women with POF have an immune reaction against their ovaries and might be at risk to get immune reactions against other endocrine glands, particularly the thyroid gland and the pancreas. Thyroid problems and diabetes could arise and should be detected very early if women with POF are checked from time to time for these sorts of problems.

8. Can the birth control pill cause POF?

There is no evidence that birth control pills cause POF. If you look at a very large group of women and examine the reasons for loss of periods whether they were on the pill or just came off the pill, the percentages of women with each of the possible disorders is identical regardless of pill use. They have the same sorts of problems in the same sorts of percentages as women who never took pills, including disorders like POF. That's the basic way in which it was determined that pills don't cause POF. POF appears once a woman stops the pill because the pill supplies hormones to the uterus that will result in a monthly period. If you independently for whatever reason run out of eggs while you are taking the pill, there is no way for you to know. If your head was chopped off, but you could still take pills, you would get a period every single month despite having something dramatically wrong with you (sorry about the tasteless example!)

While you are taking pills, your ovaries are not producing hormones, but the pills are giving you plenty of hormones, so you will get regular periods and won't have vaginal dryness or hot flashes. Those problems won't start until after going off the pill. Then, when your estrogen levels get low, the symptoms appear.

9. Do doctors believe that this condition is so untreatable that its cause does not even need to be determined?

There is no scientifically based evidence to support any treatment for POF. Therefore, in most cases, doctors recommend HRT if your periods are sparse, and egg donation if you want to get pregnant. However, a small number of women with POF can get pregnant and do so unpredictably. The search for underlying causes is usually not productive. Genetic causes can be found, but don't really require treatment. About a third of women with POF won't have any detectable cause. However, about a third of women with POF will have evidence of an autoimmune process underlying the disorder. This means that there will be evidence that the body has made antibodies to endocrine organs (like the ovary). If these antibodies are directed against important glands, like the thyroid gland, you will need to take hormone to replace what may be missing from the thyroid or other organs. For this reason, you should be checked for these sorts of problems if you have POF. Starting HRT is a wise policy as a long-term strategy but is not a medical emergency. However, if you are not being checked for autoimmune problems, you should be.

10. What kind of research is presently being done to help women with POF?

Experimental research is being done in which a woman uses a donor egg and has the nucleus of her own egg injected into the donor's egg. This is in the early stages at present, it has not been tried in animals before bringing it to humans as far as I can tell, and it does raise a series of troubling questions about how it might work and what could go wrong, as does all of this sort of stuff. I don't believe that it is a technology ready to be used by women with POF. The place where this work is being done is New York University.

There are other investigators who have been trying to find medical treatments for POF for years. Unfortunately, none of these medical treatments work, but it's important to know the negative results sometimes, just so you don't go pursuing those sorts of options.

11. Do you have any opinion or experience with acupuncture to treat hot flashes and other symptoms?

My impression about acupuncture would be that it probably can't hurt, but there is not evidence to demonstrate that it is effective treatment for hot flashes, as far as I know. There is no defined research proven role for acupuncture in this disorder (POF). It has not been proven to be effective and it has not been proven to be ineffective.

12. Are there any new medications on the horizons that might help us POFers?

There are no new medications that are appropriately considered 'treatments'. There are a bunch of things that good scientists have now demonstrated to be worthless, and I would avoid wasting your time on them: estrogen (not for HRT which is a good reason to take it, but for the purpose of 'reversing' the POF), Lupron or Synarel, steroids, danocrine, high dose FSH...Unfortunately, in the search for what might work, all that's getting turned up is what doesn't work. The National Institutes of Health is in the process of doing clinical studies on women with POF. If you are interested in volunteering, you might be able to advance research in this area, but you will not have any guarantee that the latest thing being tried will work. You also may receive a placebo, in which case it would not be expected to improve your chances of ovulating or pregnancy at all.

13. Will POF cause a "premature aging" or a decreased life expectancy?

That is a very common fear of women with POF--far more common than I had imagined before getting on the net--but let me reassure you that that is NOT the case. I have spent many years doing research on the biology of women with POF. I have actually specifically been looking for evidence that other organ systems are prematurely aged in the hope that treating those problems might improve the ovary. Every organ system I have looked at is age-appropriate--including the growth hormone axis, the adrenal glands, the stroma of the ovary (not the part with follicles), the pituitary gland, the lining of the uterus, everything else functions in an age-appropriate way--only the follicles have gotten old before their time!

14. What should estrogen levels be on day 3?

Estrogen levels can vary quite a bit on day 3. They can be as low as 20 or as high as 100. If an estrogen is over 80 in my lab on day 3, it indicates that woman is maturing a follicle too fast. Sometimes that is a sign of impending problems with ovulation and usually is accompanied by a high FSH. A very low estrogen on day 3 might also be a problem, but most commercial ways to measure estrogen are not good enough to tell apart 'normal' low from 'abnormal' low levels on that day.

15. I was quite shocked to find that autoimmune disease is thought to be the cause of POF. Why do doctors believe this is the case when so little research has been done on POF?

It looks like about a third of women with POF have evidence of other autoimmune disorders. Most of these autoimmune disorders involve antibodies against other endocrine glands in the body. The thyroid gland is the most common one to be affected. More rare are cases of POF with associated rheumatoid arthritis or systemic lupus. There's simply not enough people with these associations to learn much more about it.

Don't be too discouraged--research IS being done about these conditions. Doctors have been trying for years to figure out how autoimmune disease can cause POF. There are no answers yet.

16. Would it be better to find an endocrinologist/OB in addition to or rather than my OB/GYN? Would I get better care?

Depending upon your doctor, you may be perfectly fine with a general Ob/Gyn. A Reproductive Endocrinologist specializes in hormonal problems in women. You may get a more thorough initial workup from a Reproductive Endocrinologist, or your Ob/Gyn may suggest a consultation with one just to go over your case and plan management. I suggest that you see a Board-Certified Reproductive Endocrinologist. That just means they completed a Fellowship and passed the examination given by the American Board of Ob/Gyn.

17. Can you explain the differences between POF and Polycystic Ovarian Syndrome?

If you had polycystic Ovary Syndrome, your FSH level would be normal or low. Along with this problem, there is often (but not always) obesity and excess hair growth somewhere on the body. If you are overweight and had abnormal cycles, you might have been inappropriately been given this diagnosis. Women with polycystic ovary syndrome tend to have elevated levels of testosterone in their bodies, not nearly as much as men but more than most women do. This leads to some other changes and there are metabolic disorders that these women tend to have. It is possible to have polycystic ovaries that have undergone an early menopause, so everyone might be entirely correct about you, and you could have both problems.

If you had POF all along, there ought to be a telltale elevated FSH if it was done, during your workup for skipped periods. Women with POF will also have evidence of symptoms from low estrogens, like hot flashes, women with polycystic ovaries will not have these symptoms.

18. What is the daily dosage of Calcium you recommend for women with POF?

Calcium should be taken in doses similar those recommended for postmenopausal women 1200-1500mg per day. All the calcium on the label is NOT what your body absorbs, only about half of it gets in, so be sure to take MORE than the 'dose' on the package. The cheapest, easiest way to take calcium is in the form of TUMS. Three to four TUMS EX tablets a day (they are chewable) should cover you, in addition to what you take in your diet. Take at least half of your calcium at night before bedtime, it works better. If calcium carbonate (TUMS' calcium) does not agree with you, citracal and caltrate are alternatives but they are expensive. Other forms of calcium have not been looked at with respect to reliability, but are probably OK. Much is made of a 'need' for magnesium in the lay press. There is not very good scientific evidence that magnesium deficiency is a public health hazard. So mostly you should concentrate on calcium.

19. Could you please explain the difference between POF and perimenopause? The symptoms and fluctuating hormone levels seem to be identical. Is it just a matter of age?

Your question is a good one, people are actively investigating this very question. It does appear that the processes and annoying side effects are similar between POF and perimenopause. However, with POF there is a substantial chance of 'recovering' a cycle here and there without warning. With perimenopause, once a woman over the age of 45 has gone a yearwithout a period she is very unlikely to ever have another period for the rest of her life. This is not true with POF. The younger a woman is, the more likely she is to have a cycle off and on. That's a general rule.

The reasons for you to take estrogen at a young age is that is what your body would be making if you didn't have POF. Without estrogen you are likely to have loss of bone, and you will have loss of bone for many years before you reach the 'normal' age of menopause. The best studied bone protective dose of estrogen is Premarin 0.625. You could try lower doses, but you should have your bone density checked to be sure you are not still losing bone if you try a lower dose.

20. After an ultrasound I've been told that my uterus is atrophic. What does that mean?

Atrophy is a very powerful word, and when an ultrasound shows a small uterus, it's often called 'atrophic'. This brings up images of a little old lady's uterus in the body of a young woman, and it makes people upset. The uterus is incredibly responsive to hormonal stimulation. The tiny uterus seen in a preadolescent girl or a postmenopausal woman would grow in days to weeks if the person was given a little estrogen. A small uterus just means that your estrogen was low, possibly very low, on the day of the scan and for maybe a week or so beforehand. It means nothing else. It doesn't mean your uterus is irreversibly damaged, or prematurely aged, and you can bet that it will grow if given some estrogen.

The actual dimensions of the uterus are usually not an issue for most women. There are not a lot of reported cases of a uterus too small to carry a pregnancy, and this is not a known clinical problem.

21. Is this reversible?

POF is usually not reversible, but in women with autoimmune problems and in most cases of POF, some evidence of function of the ovaries happens from time to time. Your daughter might cycle again off and on for a period of time. Overall, though, she is unlikely to get her periods back for more than a few months at a stretch.

22. I've seen some reference to autoimmune and POF? Like what? Should I be checked for something?

About a third of women with POF have evidence of auotimmune disorder(s). The most common problem by far is thyroid gland autoimmunity. In this process, the body makes antibodies against the thyroid and eventually the thyroid gets destroyed by the antibodies. If this is happening to you, it is desirable to pick it early and you will probably eventually wind up on thyroid replacement. This is a common problem in women about 1 in 20 has this process going on anyway, but it's even more common in POF. The best way to check is to check for thyroid antibodies and to check thyroid function with a TSH level. You should be checked every few years if it is normal now, just to make sure it doesn't happen later in life. There are many other autoimmune disorders, but most of those have symptoms associated with them and your doctor can screen you for them based on your clinical history. A general chemistry and blood count panel provides good information about most of the other autoimmune problems that might happen.

23. Do you have advice for how husbands/partners should deal with their wives on this?

It's difficult to overestimate the stress that this disgnosis causes women. Social scientists are just beginning to scratch the surface. Try to understand that this is striking your partner at her core and she is likely to go through a period of reactive depression of some sort. Everybody learns to cope with this diagnosis, but it's not an easy row to hoe. If she seems like she is getting depressed and she is willing to go for treatment, either talk therapy or medication, I would encourage you both to go for it and remain supportive. It's a terrible loss for a woman, as this Internet line keeps teaching me every day!

24. How can I treat a case of Premature Ovarian Failure?

Your question is a very complex one. Premature ovarian failure usually means that the ovary no longer has enough follicles (or eggs) within it to let you ovulate and menstruate regularly. There is no known treatment for the underlying problem of the ovary. To get pregnant with this condition usually involves luck, unless a woman wants to do oocyte donation and use a 'borrowed' egg from another woman who has an abundance of eggs. Oocyte donation works well at achieving pregnancy, usually better than 50% per attempt. Otherwise, women with premature ovarian failure are likely to get into trouble without some form of hormone replacement (that is, in women who are not interested in getting pregnant). So that is usually recommended. It is also important to be taking calcium and probably checking bone density earlier in life than one would ordinarily do this test. Certain other conditions that are rare ought to be ruled out and the thyroid gland should be checked.