Historically, it has most often been assumed that when a woman enters perimenopause and begins to experience symptoms which include hot flashes, it means she needs estrogen. However, a woman’s estrogen levels do not decline until the last 6 to 12 months of perimenopause. When she first enters perimenopause, estradiol levels usually rise slightly. The hot flashes that she experiences at this stage of life are not caused by a lack of estrogen.
Elevated FSH Does Not Indicate Estrogen Deficiency
Many health practitioners were taught to measure FSH levels to confirm that estrogen levels were low. However, estrogen has been shown not to be the major controller of FSH. FSH is controlled primarily by inhibin, a hormone produced in the corpus luteum. When a woman does not ovulate, she does not produce a corpus luteum or inhibin, and the FSH rises due to a lack of inhibin, not a lack of estrogen. Progesterone is also produced by the corpus luteum, so elevated FSH is reflective of a decreased production of progesterone. A physiologic amount of progesterone is required to make estrogen work correctly. In early peri-menopause, a woman’s hot flashes are most often caused by a lack of progesterone, not a lack of estrogen.
When Does an Estrogen Deficiency Symptom not Indicate Estrogen Deficiency?
Although progesterone is a key in obtaining optimal effects of estrogen, other hormones may cause or influence the symptoms we often perceive as a lack of estrogen. High cortisol levels can also cause weight gain, irritability, irregular cycles, and hot flashes even in the present of normal estrogen levels. Consistent low cortisol can also cause or aggravate hot flashes. Low thyroid function can cause similar symptoms that appear as estrogen deficiency; insulin resistance can do the same. Over the recent years, one of the largest changes in the approach to obtaining physiologic hormone balance in women is the way estrogen replacement is approached. Since so many other hormone levels affect estrogen and estrogen receptors, correcting other hormone issues have led to further and drastic reduction in the amount of estrogen commonly administered. In other words, if the other hormone or endocrine issues are addressed first, then the amount of estrogen required to treat the assumed “estrogen deficiency” symptoms becomes smaller.
No symptom or set of symptoms guarantees a woman needs estrogen, as some symptoms can be explained by another possible hormone deficiency. Vaginal dryness or atrophy, which almost always indicates a lack of estrogen, can exist when estrogen levels are normal. Vaginal tissues are also supported by testosterone and thyroid, and a significant deficiency in one or both of these hormones can be the source of the problem. Lack of progesterone could result in the estrogen not being effective. Properly assessing estrogen need and assessing response to estrogen therapy requires balancing the other endocrine hormones simultaneously or prior to estrogen administration.
Although most of the time, measurement of estrogen levels via testing is very accurate, there is a small window of time in woman’s life when it may not reliably indicate estrogen need. Estradiol levels begin to fluctuate during perimenopause, with much wider vacillations towards the end of perimenopause. During this period, proper measurement of all other hormone levels along with symptom assessment should be reviewed. The best approach would be to correct deficiencies or issues with progesterone, cortisol, thyroid, insulin resistance, and nutrition or lifestyle, then correlate remaining symptoms with levels, and address estrogen therapy as required.
How Much Estrogen is Just Enough?
Historically women have been given too much estrogen even when they do need estrogen replacement. Excessive estrogen may help control the hot flashes for a month or two, but eventually the symptoms return. A surplus of estrogen causes the same symptoms as insufficient estrogen, just with a slight time delay before the symptoms return. Too much estrogen at first increases the number of estrogen receptors, but after a period of time the body decreases the number of receptors, so the estrogen cannot work properly no matter how much is there.
Premarin® 0.625 mg or Estrace® 0.5 mg, dosages commonly administered for years, are excessive estrogen burden for any woman. The majority of estradiol given by mouth is converted to estrone, another strong estrogen. Estradiol levels resulting from these doses may be at normal premenopausal levels, but estrone levels will be significantly higher than normal. High estrone levels lead to symptoms of estrogen dominance and significantly increase the risk of breast cancer. Premarin® contains 50% estrone, and 5-19% estradiol (along with a bunch of horse estrogens!). The estradiol in it for the most part is quickly converted to estrone, so what the patient is really receiving is a strong dose of estrone. While Premarin® produces normal premenopausal levels of estradiol, estrone levels are usually 7-10 times higher than they should be. Clinicians usually only measure the estradiol level to manage therapy.
Estrace® is bioidentical estradiol, but again the usual doses given by mouth produce too high an estrone level , usually 3-5 times higher than normal.
Topical administration of estrogen is safer and enables administration in a manner where the correct ratio of estradiol to estrone can be accomplished. Topical administration is a very efficient manner to deliver hormones, so compared to the oral route much lower doses are required. But because many practitioners have erroneously assumed that venous blood measurement can be used to determine the amount of topical dosing, doses much higher than physiologic amounts are too commonly used.
Testing Estrogen Levels
Capillary blood or saliva testing must be used with topically applied hormone to get a true representation of the amount of hormone that is being delivered to the tissues where the hormones work. Too often excess hormone is used based on serum testing, then the symptoms return as a result, and then even more hormone is given. Symptoms of too much of any hormone are very, very similar to symptoms of too little of that hormone! If the hormone has worked for a period of time, and is no longer effective, it is usually a good indication that too much hormone has been administered.
Keys to Physiologic Estrogen Replacement Therapy
- Make sure the patient needs estrogen by correlating symptoms with measurement of levels.
- Never assume a woman needs estrogen.
- Always restore progesterone to a physiologic level before assessing how much, if any, estrogen is needed.
- Test cortisol with a 4 times a day saliva test to help determine adrenal influence on “estrogen deficiency” symptoms. Address as necessary.
- If symptoms of hypometabolism (hypothyroid) are present, test the TT4, fT4 direct, fT3 direct, TPO and TSH to properly assess. Address appropriately.
- Check insulin resistance if symptoms indicate and address appropriately.
- Always start very low on estrogen dosing and make changes slowly.
- Take steps to ensure safe estrogen metabolism by optimizing liver conjugation, bowel elimination, methylation and glutathione conjugation, and by reducing lipid peroxidase activity.