It is well accepted that diabetics need insulin therapy (hormone) and that thyroid hormones are needed when there is low thyroid function. The general public knows less about replacement of pituitary or adrenal hormones but finds such treatments acceptable, especially when a known person or celebrity needs such therapy, e.g. adrenal hormone replacement needed by President John F. Kennedy. It is clear that physicians as well as the general public find hormone replacement therapy for a failing endocrine gland such as thyroid, pituitary, or adrenal, perfectly acceptable. It is ironic that at the same time, hormone replacement therapy for a failing gonad (ovary or testicle) is found controversial.
The risks of Hormone Replacement Therapy have been overemphasized and the benefits downplayed. Adverse side effects seen with specific hormones and oral route of administration are generalized to all hormones regardless of how they are administered. The effect of confounding factors, e.g. environmental, genetic, or dietary on the type and frequency of side effects is consistently ignored. Practicing physicians frequently have to fend-off unexpected questions and concerns from frightened patients who listened to another incomplete or premature media report and decided on their own to discontinue hormonal therapy. The benefits of hormonal treatment, because they are long term and difficult to evaluate and prove, are easily ignored. The only obvious effect of hormonal treatment is control of the menopausal symptoms. The medical establishment, motivated as much by medical as medico-legal concerns, cautiously recommends hormonal treatment only for menopausal symptoms and only at the lowest estrogen dose and for the shortest period of time, as indicated in recent “Position Statements” of several medical societies.
In the 1990’s and early 2000’s, reports began appearing on the increased risk of breast cancer, thromboembolic disease, myocardial infarction, and stroke as possible side effects of “hormone treatment”. Unfortunately, the reports, editorials on the studies, and the media referred to “hormone treatments” without identifying specific estrogens used, their route of administration, use with or without progestogens, and the onset of treatment in relation to menopause. It became subsequently clear that all of these factors played a significant role and each one contributed to the erroneous interpretation. Unfortunately, the damage was done and thousands of women stopped HRT while mainstream physicians, concerned of legal implications, stopped prescribing hormone replacement. New and reanalyzed data suggested that it was progestogen in Prempro that increased the risk of breast cancer and that oral administration was the reason for thromboembolic phenomena; while late onset of HRT when atherosclerotic changes had already developed, contributed to the increase in cardiovascular events. It also became apparent that not all estrogens have the same effects in different tissues and that there is a difference between synthetic and “natural” estrogens. In the resulting confusion, differences between different estrogens, bioidentical (physiologic) or synthetic; between progesterone and progestogens; and between oral and parenteral administration became lost and all “hormones” acquired a bad reputation.
I recommend hormone replacement therapy for women as well as men going through cessation of the gonadal function. The objective is not only to control symptoms of hormone deficiency but also to prevent gradual mental and physical deterioration and development of chronic debilitating diseases that we typically associate with aging. I am strongly in favor of “bioidentical” hormones although not necessarily those prepared by the compounding pharmacies. The term “bioidentical hormone” has been corrupted and misused by both sides in the ongoing controversy. Estrone and estriol as well as weak androgens, e.g. DHEA or delta 4 androstenedione, are also bioidentical to women. I use them for specific reasons, keeping in mind that the ratio of these hormones in the woman’s body may have physiological relevance. Estrogens of animal origin (e.g. Premarin) are bioidentical to these animals (e.g. pregnant mares) just like phytoestrogens are bioidentical to plants. They are not bioidentical to women and their effects differ. However, they are also “natural” as opposed to “synthetic” estrogens produced by the pharmaceutical industry. Synthetic estrogens have advantages for specific indications but I do not recommend them for hormone replacement.
Estradiol, a bioidentical hormone, is available in several forms as pharmaceutical or compounding product. I prefer transdermal patches produced by several companies; creams, sprays, gels, vaginal products, and intramuscular injections of estradiol are also available. Transdermal, intravaginal, or intramuscular administration has several benefits. The hormone is first absorbed into the peripheral circulation from which is it picked up by the tissues and only then, in contradistinction from oral estrogens, has the effect on the liver. Oral estrogens are first absorbed from the gastrointestinal system into the liver where they are detoxified (that is why they are needed in large doses) and where they stimulate synthesis of a variety of proteins. Of most concern is increased production of clotting factors which may lead to thromboembolic phenomena, intravascular clotting, myocardial infarctions, stroke, etc. Furthermore, even oral estradiol micronized to facilitate absorption is converted in the garointestinal system to estrone and predominantly in this form, enters the peripheral circulation. Estrone at the higher blood level than estradiol is not physiologic for women; it is seen in various disease states such as polycystic ovaries and may be responsible for thromboembolic phenomena and other side effects. Another major advantage of transdermal ERT with bioidentical estradiol is that it can be measured as such in the peripheral blood. I can correlate the dose administered with the blood level and the effect on symptoms, physical changes (skin, mucous membranes, subcutaneous tissue, bones, joints, etc.), or markers for bone resorption, atherosclerotic changes, etc.
Cyclic progesterone for 7-10 days should be considered in women who have their uterus to induce periodic endometrial shedding and to prevent overgrowth of the uterine lining. Alternatively, the dose of estrogen should be adjusted downward which is quite easy with estradiol measurement in the blood. To this HRT regimen, I add testosterone cream which acts synergistically with estrogen on menopausal symptoms and bones, improves psychological well-being, counteracts depression and mood swings, and improves sex drive and sexual satisfaction.
Risks and complications of hormone replacement therapy can be attributed to the use of inappropriate (non-physiologic) hormones, oral (non-physiologic) route of administration, or erroneous (non-physiologic) hormone combinations such as estrogens with progestins or initiation of hormonal treatment well past menopause when cardiovascular changes have already begun. It is important, however, to keep in perspective the frequency of such events and the contributory factors.