Hormone and Estrogen Replacement Therapy Problems

HRT and feedback problem

I have been in surgical menopause for almost 3 years and continue to have problems (hot flashes, night sweats, insomnia) with my hormone replacement therapy (HRT). I use .75 Vivelle® Patch and 3 Estratest H.S.® pills per week. The testosterone in the Estratest H.S.® has helped decrease these symptoms, but 3 pills is all I am able to tolerate without getting acne and vaginal dryness. When we increase the estrogen trying to get rid of the remaining hot flashes, etc. it makes things worse instead of better. My OB-GYN says I have a feedback problem, and that something appears to shut down or off with the increase in estrogen. However, she isn't sure how to fix the problem. What does she mean about a feedback problem? Any ideas on how to correct or find someone who could help me solve this problem?

As the estrogens go up, the hotflashes should go away. Have you had a blood (serum) estradiol level drawn? The reason I ask is that sometimes estrogen replacement can get too high while chasing hotflashes and the high levels actually cause stress-related hot flashes. I've seen this in some women and they actually need to decrease levels of HRT.

Also keep in mind there are other causes of hotflashes. They are listed at hot flashes causes. They include: hyperthyroidism/thyrotoxicosis anxiety, panic attacks, carcinoid syndrome, pheochromocytoma, drugs, diencephalic epilepsy, tuberculosis, and malaria. If your serum estrogen level (usually estradiol) is normal, your doctor may need to look for some of these other causes.

Recently my estradiol level was 79 pg/ml; we again tried to increase estradiol with the same response - more intense and frequent hot flashes, night sweats, insomnia, etc.

What are normal estradiol levels?

Normal estradiol levels depend on the laboratory and units it's reported in. In menopause, the range may be 10-20 pg/ml or 40-70 pmol/L. In normal reproductive age women during the menstrual cycle, estradiol levels range from 50-400 pg/ml.

In our lab, values under 100 pg/ml can be associated with hot flashes so if your levels are the same units, you might need more estrogen as your doctor has indicated.

What different preparations have you tried other than the patch and the Estratest®?

I have tried Premarin® and Estrace® and Estraderm®, Climara®, and Vivelle® patches in various dosages and combinations of dosages.

These are all estradiol products and conjugated estrogens. Did you try any Estratab®, which is estrone synthesized from plant steroids?

Right now my total estrogen dosage is 1.2 mg counting the Vivelle® patch and the estrogen in the Estratest®.

This is not an excessively high dose. In fact for surgical menopause (ovarian removal) most women require the equivalent of 1.25 mg Premarin®.

I wouldn't want to add more since much of what I read indicates .625 mg (Premarin) or 1 mg (Estrace) or .5 (patch) is the dosage which is less likely to cause side effects with long term use.

Your website mentioned estrogen sensitivity. What is that?

There can be a variability of each tissue's sensitivity to estrogen. Some women will get moderate breast pain before reaching doses that relieve hot flashes. Others may have nerve or skin tingling at very low doses. Others will have irritability and headaches but still have hot flashes. Some women may take very high doses but still have vaginal dryness. If endometrium is quite sensitive, women with a uterus have bleeding at low doses.

Could I be sensitive to estradiol increases since my system seems to go haywire when additional estrogen is added even though blood work indicates that my estradiol level is not high.

Yes. There can be an effect at the central nervous system level, involving catecholestrogens.

By the way, we did try to reduce the dosage of estrogen to 1/2 of what I'm on now. My FSH level shot up to 130, hot flashes, night sweats, insomnia intensified and I developed a severe case of atrophic vaginitis.

This would imply you are on the best dose now that you can get and any residual hot flashes should be treated with nonestrogen methods or just tolerated. I'm still concerned you may have something like a thyroid abnormality, carcinoid or pheochromcytoma going on. These need to be ruled out.

My previous FSH test about 2 1/2 years ago was 134. It is now 10. I assumed the change in FSH means I am no longer in surgical menopause.

This doesn't make sense at all. The FSH almost always stays elevated for quite awhile after menopause. I would be concerned that the lab got the wrong specimen and ask your doctor to repeat it.

What suggestions might I try from here?

You may ask your doctor for trial of clonidine, which is an antihypertensive that is sometimes used to control hot flashes. It is nowhere near as good as estrogen for most people but it has been sucessfully used as a substitute. The transdermal clonidine patch (0.1mg/day) reduces the frequency of hot flashes by 20% and the severity by 10%. You can see why this isn't often used, but in your case it might help.

Another regimen to consider is the Estring® vaginal ring which is placed in the vagina each 3 months. It delivers a dose to the vaginal epithelium and maintains moistness very well (it has estradiol as the active agent) but at the same time does not appear to absorb much systemically. At least it does not change serum estradiol levels. Then try the Estratab® at a 0.9 equivalent and go up to a 1.25 level if you are still having hot flashes. You may even possibly change your Estratest h.s. dose (increase) since you will not have to worry about too much vaginal dryness. Yours is a difficult problem and the only way to diagnose your sensitivity and feedback problems is basically through trial and error using different medications.

Age 20, pituitary tumor removed, ERT risks and benefits?

Please advise risks and benefits of estrogen replacement therapy for a 20 year old female who has just underone removal of pituitary tumor. Periods have not commenced and have been missing for the past 6 -8 years.

This is an unusual cause of premature menopause but a serious one because you will spend 30 more years in the menopause than most women. See the effects of menopause and estrogen replacement therapy at menopause.

In your case the risks are likely to be much greater if you do not take estrogen replacement. With pituitary tumor removal you will be on replacement of other hormones such as thyroid and adrenocorticoids.

Most gynecologic endocrinologists would recommend long term estrogen therapy. Assuming a uterus is still present, progestogen therapy is also needed. I'm sure you have physicians who are managing this. The major benefit of hormone replacment is to prevent premature heart disease, bone thinning and general aging. The major risk would be possible breast cancer with long term use (probably about 15% lifetime chance instead of 10% lifetime chance) altho your circumstances are different and that increased breast cancer risk might not be as likely in you (if it exists at all). You will spend so many years at less than normal estrogen levels (because replacment levels are usually lower than natural levels).

Why is progestin needed if the uterus is still in?

I am taking Premarin® after my hysterectomy. Recently I was talking with a group of women friends and one of the ladies went through menopause and is 60 yrs old. She takes estrogen and progestin, I understand you only take progestin if you have your uterus, our question is why is this so?

In women that still have a uterus, progesterone (progestin) is needed to block the stimulation of estrogen alone on the lining of the uterus. If this isn't done, in the long run over 5-15 years, a woman with a uterus and taking only estrogen is at increased risk (2-3X) for uterine (endometrial) cancer.

I did have my ovaries removed, at age 43, because of a history of cancer in my family. Does this mean I may experience some menopausal symptoms until my hormones are regulated?

Yes. Hotflashes, night sweats, sleep disturbances, vaginal dryness and sometimes irritability are among the most prominent direct menopausal symptoms. If you are taking estrogen replacement, however, most of these are under control. Most of those symptoms, except vaginal dryness, go away eventually without estrogen but it is quite variable among different women. Those symptoms may last 6 months, 6 years or even 20 years. About one half of women don't have them at all.

I was speaking to my mother now 68 years old and she said after her hysterectomy (complete) the doctor only had her on hormones for 6 months and said because of cancer risk she didn't need them. Every Doctor I have spoke to said it is very important to take estrogen to maintain health?

The only cancer risk with estrogens may be with breast cancer and even that's somewhat questionable. See our menopause article and test at menopause description.

Estrogen does have beneficial effects other than relief of hotflashes, etc. It seems to protect against athersclerotic heart disease by raising high density lipoproteins (good cholesterol) and lowering total cholesterol. It decreases bone loss and bone thinning (osteoporosis) which can prevent hip fractures in later life. It also looks as though Alzheimer's dementia incidence may be decreased. So there are many reasons to take estrogen replacement even though you may not be having hot flashes very much.

What is Natural HRT?

There's a lot of hype or perhaps should I say "sales pitches" regarding the use of natural (not herbal) vs synthetic HRT and I would like some help sorting out the facts.

From what I understand, there are 3 types of estrogen--estriol, the good one that blocks the effect of estrone, which is the bad one that facilitates cancer of breast and then there is estradiol, which I can't find too much about other than the fact it's the drug I take. And then we have conjugated estrogens (Premarin, Climara) which are converted to estrone in the intestine. I am certainly confused.

I don't mind going the natural route, but if they're all converted to the same thing why bother? Also, in a surgically menopausal woman, do you think the addition of natural progesterone and testosterone would be beneficial? I don't want to turn into a passive old woman because my hormones aren't where they're supposed to be.

The compounding pharmacist in my town said he'd read up about the use of triple estrogen, progesterone, & testosterone - however he's reading from a book published by one person.

Are there any controlled studies that I could read about before making a decision to switch?

Before I can get you some information about studies, I need to know what you consider "natural". I don't blame you for getting confused because I get confused by marketing people.

In the reproductive age woman, the naturally occuring estrogen is estradiol from the follicle development in the ovary. It is the most potent of the estrogens milligram per milligram and the main one that stimulates the endometrium, breast etc. Estrone and estriol are metabolites (by products) of estradiol as it is broken down by the body. They both have estrogen activity but they are very weak estrogens and take very large amounts to have any estrogen effect in women. After menopause, there is no more estradiol around but estrone can be made in large amounts by fat tissue to begin having some estrogen effect. Obese women after menopause tend to have less hotflashes and less vaginal dryness than non-obese women who are not taking estrogen replacement. Perhaps this is where you heard it was a bad estrogen but truthfully it is not. Estriol is in less quantities than either except in pregnancy when the metabolic pathway shifts to produce more estriol as a by product of estradiol. None of these three estrogens are considered "bad" or "good" that I know of, just different in potency. You could take any of them for replacement in the right doses and they shouldn't have any differential effect on breast, or endometrial tissue.

Now, what is "natural". Premarin actually is the most natural of all the estrogen sources if you consider pregnant horses as a part of nature. In their pregnancy, the horse estradiol is converted to many different estrogen metabolites (conjugated estrogens, the majority of which is estrone (same chemical structure as the estrone in humans) along with over a dozen other metabolites, most of which do not occur in humans but which have some estrogen potency. In fact one of the metabolites is thought to have a major atherosclerosis prevention effect.

Plant estrogens (phytoestrogens) may be considered "natural" and in that case, humans metabolize certain plant substances into metabolites that have weak estrogen effects. If you get a high enough amount of these plant substances from soy, clover and alfalfa, you can use them for estrogen replacement. Up to now it has been impossible to contol the dose to make the same estrogen potency from pill to pill because these plants vary in their content depending on soil, climate and variety conditions. Also, even if you have a standard amount of milligrams, you have to test for the biologic potency which most manufacturers don't. These would fall under the category of "herbal".

There is also a claim going around that estrogens, progesterone and testosterone are made from substances in Mexican yams. That is true but they are synthetically made by a chemical reaction using the "natural" substance as a precursor. If you or I eat Mexican yams, our bodies CANNOT convert the plant steroid, diosgenin, to estrogen, progesterone or testosterone. It takes a synthetic process.

Therefore does this mean that substances made from the Mexican yam are synthetic or natural. Are estrogen substances that don't undergo any chemical conversion but are the natural metabolites of female horses natural or "unnatural". You see why it is difficult and why you have good reason to be confused. Now you need to answer what you mean by "natural" and actually why you are interested in a "natural" product. Is it the purity of substance you want or the closest to what women naturally have in their bodies?

Thank you so much for the information. The old brain is always thinking and I thought that perhaps my body would absorb "natural" better that "synthetic" (premarin). I guess if you chemically alter a natural product you have synthetic, right??? Are all manufacture's brand of estradiol absorbed by the body the same?

All estrogens suffer from poor to good absorption in the stomach when taken orally. The estradiol preps in pill form are the same although some manufacturers micronize the estradiol and that makes it absorb better from the gastrointestinal tract.

For the injections, most estradiols are the same but the carrying agents are different with different manufacturers. That can explain variable absorption.

Systemic Lupus (SLE) and replacement therapy

I'm 45 & suffering miserably from insomnia, palipations, hot flashes & night sweats, vaginal dryness with inflamation and low libido after TAH/BSO 9 weeks ago. I have tried Premarin .625 then 1.25, 1 cc inj estradiol (had great relief for 8 hours or so) supplemented with Climara & Premarin cream, then switched to Estratest. Consulted new gyn and given 1.5 cc inj depo-testradiol (unsupplemented) - good results as well but for only a few hours. Some of the symptoms subsided after a few days only to return 1 week later. Last dose was 2cc inj of depotestradiol which took 48 hours to the dot to work and lasted just 5 days. I'm scheduled to have another 1 cc injection in 10 days and every 2 weeks thereafter. Do you have any suggestions?

It sounds as if you are not absorbing the injections well but as the doses get higher, there is slightly more relief. This needs to be monitored with serum estradiols when your symptoms are controlled and then after, when the symptoms return. If your blood estradiol levels are low when symptoms return, that indicates poor absorption. If the estradiol levels are actually high (greater than 100 pg/ml) then you have a decreased sensitivity of the end organs.

About 3 weeks after surgery, estradiol levels were 76 on 1.25 mg of premarin...sounds like I need to have some lab work again. I also have mild SLE (no kidney involvement) and read that we "lupies" metabolize a certain estrogen differently. Could that be some of my problem?

Yes. There is some sort of difference of metabolism of estrogens with lupus. Also some studies imply a higher level of estradiol in lupus so this may mean after menopause you actually do require higher levels of estrogen to get the same effect. This is a form of lowered estrogen sensitivity, i.e., the tissues are not as sensitive to estrogens so larger levels are needed.

Also, what does "decreased sensitivity of the end organs" mean and if that's my problem, what's the solution?

See above for decreased sensitivity. Solution may involve different estrogens than estradiol.

If I could just settle down and get some rest, maybe everything would fall into place. Do you ever recommend antidepressants to women who have these symptoms?

Yes. Also antianxiety meds. Occasionally sleeping meds. The sleep deprivation alone can give many menopausal symptoms.

Does HRT increase the risk for having a blood clot?

I am concerned that menopausal hormone replacement can cause blood clots just like oral contraceptives can. Is this true?

Postmenopausal estrogen replacement has a very low risk for blood clots or vascular occlusion leading to heart attacks. The risk is about 4 per 10,000 women compared to about 1 or 2/10,000 women not taking ERT. The risk goes up, however if you already have coronary artery disease to about 3- 4/1000 women. There is a subgroup of women, however, who are at much higher risk for thrombosis if they use estrogen replacement.

Certain women have a genetic risk for developing blood clots, pregnancy vascular complications and strokes or clots to other body areas. These genetic variants go under the weird names of factor V Leiden, prothrombin 20210, methylene tetrahydrofolate reductase (MTHFR677) and factor V HR2 haplotype. By far the most common is factor V Leiden deficiency. Women who have anticardiolipin antibodies have a higher incidence of this.

Only about 6% of the Caucasian population and 3% of the African-American population have these genetic changes. In one study, postmenopausal women who had previously had a heart attack (myocardial infarction) were followed for 3 years and analyzed for hypertension and factor V Leiden and prothrombin 20210 GA variants.

They found not only that women who have hypertension have a higher risk of heart attacks but those who had hypertension and the genetic variation AND took estrogen replacement were at an 11-fold risk for non-fatal heart attacks.

These findings have been confirmed in other studies and the net result of this is that if you have had a history of blood clots, stroke, other vascular thromboses or pregnancy abruption problems, then you should consider asking your doctor to check you or refer you to be tested for, factor V Leiden factor deficiency. This test is a cDNA-PCR test of the prothrombin gene (about $150). If you are positive, you should avoid taking hormonal replacement therapy.