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1 Clinical Application of BHRT Tracy Marsden BScPharm, DHPh 2 Types of Hormones Estrogens Progesterone Testosterone Cortisol & DHEA 3 Pre-Menopause OVARY Testosterone Progesterone aromatase Estradiol Estrone Estriol 4 Estrogens 3 main types: estradiol, estrone, estriol. Estradiol is the main estrogen produced by the ovaries. Estrogen receptors found throughout body: brain, blood vessels, bone, etc. 5 Progesterone Synthetic progestins like Provera® are not the same as progesterone. All women need progesterone to balance effects of estrogens (even women who have had the uterus removed!) Progesterone increases the body’s sensitivity to the estrogens it has. 6 Androgens Testosterone is important to women for: Bone Sex drive Energy, sense of well being DHEA and androstenedione are important building block hormones: needed to make androgens and estrogens (particularly after menopause). 7 Cortisol Is the primary ‘stress’ hormone. High cortisol levels can interfere with the actions of all the other hormones. Prolonged elevation of cortisol can deplete the adrenal glands. 8 Post Menopause ADRENAL GLAND Dehydroepiandrosterone (DHEA) Cortisol Androstenedione aromatase Estrone Testosterone aromatase Estriol Estradiol 9 Normal Cycles Progesterone is produced in quantity after ovulation Menstrual Cycle – 6 month view Progesterone peaks after ovulation and balances estrogens. Cycles are regular. Peri-menopause – 6 month view Relative excess of estrogens over progesterone. Cycles are irregular. Post-menopause – 6 month view Very little progesterone or estrogens released by ovaries. No cycles. 11 Hormone Balance There is an intricate balance among all the hormones; too much of one can create an imbalance. Maintaining the right balance can reduce symptoms and help prevent disease. 12 Hormone Therapy Missteps Giving unopposed estrogen to all women (no progesterone given to balance estrogens) without testing or proof of need. When we found out estrogen alone increased endometrial cancer risk, we added a synthetic progestin instead of natural progesterone. When we found out synthetic progestins increased heart attack and stroke risk, we just decreased the dose. 13 A better approach THREE SIMPLE STEPS Symptom assessment Hormone testing Restore hormone balance with bioidentical hormones 14 Symptom Assessment Symptoms: Please rate your symptoms according to the following scale: 0 - never or rarely experience this symptom (<20% of the time) 1 - experience this symptom some of the time (~20-49% of the time) 2 - experience this symptom most of the time (~50-70% of the time) 3 - experience this symptom all of the time (~80-100% of the time) For example if you experience allergies some of the time, you would indicate this by darkening the 2 next to ‘Allergies’: ijvl Allergies. If you do not understand the symptom, please leave circles blank. ijkl Hot flashes ijkl Night sweats ijkl Water retention ijkl Breast tenderness ijkl Decreased sex drive Step 1: Symptom Assessment ijkl Memory lapses ijkl Foggy thinking ijkl Heart palpitations ijkl Irritability ijkl Loss of muscle bulk 15 Hormone Testing Options Urine Measures what the body throws away Blood Measures what might eventually get to tissue Saliva Measures what actually gets to tissue 16 What are bio-identical hormones? Bio-identical means that the hormones are identical in structure to what is produced naturally in the body. More accurate to call them Human-Identical Hormones, but BHRT is a common term. Studies showing harm from hormones used synthetic or semi-synthetic hormones (horse estrogens, synthetic progestins) 17 Principles of BHRT Use the identical hormone to that which the body produces on its own Give bio-identical hormones in the way that is closest to the way hormones are released in the body Use the minimum dose to relieve symptoms. 18 Bio-identical Hormone Replacement Bio-identical hormone replacement (BHRT) includes: Estradiol patches and gels oral micronized progesterone These bioidentical products are not controversial 19 Transdermal Estrogens However, BHRT also includes: compounded oral or transdermal combination estrogens (BiEst, TriEst) compounded progesterone creams compounded sustained release oral micronized progesterone . . . which are more controversial types of bioidentical hormone replacement. 20 BiEst and TriEst BiEst and TriEst contain mostly estriol, the weakest estrogen. Theoretically, estriol raises estrogens levels when they are low, and competes with stronger estrogens for receptor sites when estrogen levels are high. Some research suggests that estriol may be protective against breast cancer. 21 Bi-Est BiEst (bi-estrogen) is a combination of estriol and estradiol in oral or transdermal form Various combinations available: 80:20, 70:30, 50:50 First number refers to the estriol component 22 Tri-Est Tri-Est not used often as most women do not require estrone. TriEst (tri-estrogen) is a combination of estriol, estrone, and estradiol Various combinations available: 80:10:10, 90:5:5, 60:20:20 23 Estriol (E3) Effective for hot flashes, insomnia, poor memory. Head K. Alt Med Review 1998;Vol. 3(2) Intravaginal use may be effective for vaginal dryness, infections, recurrent UTI’s and dyspareunia. Head K. Alt Med Review 1998;Vol. 3(2) Estriol has been safely used in Europe for decades, although is not approved for use in North America. 24 TriEst and BiEst “Unconventional compounded estrogens do not appear to be worth the extra cost and effort they exact, but they do represent an addition therapeutic option for women who cannot tolerate conventional prescription estrogens.” Taylor M, Clin Obstet Gynecol; 2001 Dec;44(4):864-79 25 Bio-identical Progesterone Progesterone (bio-identical hormone) compared to Provera (medroxyprogesterone acetate) Progesterone cream versus oral micronized progesterone 26 Progesterone Acts with estrogen to relax blood vessels Does not increase risk of breast cancer Does not increase inflammatory markers in blood Protects against natural brain cell death. MPA Inhibits relaxation of blood vessels by estrogens Increases risk of breast cancer Increases inflammation causing C-Reactive Protein (CRP) Does not protect against natural brain cell death. 27 Bio-identical progesterone Oral micronized progesterone (Prometrium™) is bio-identical Effectively protects the endometrium (lining of the uterus) Giving progesterone orally creates metabolites that have an anti-anxiety and sedative effect. Pregnanolone Allopregnanolone Hydroxypregnanone 28 Progesterone Cream Progesterone cream is also effective, and may be less sedating than the oral form. Progesterone is better absorbed through skin than either testosterone or estradiol 29 Progesterone Cream Efficacy: Some evidence that progesterone cream can protect the endometrium No bone building effects May help reduce hot flashes 30 Compounded Progesterone Cream Quality depends on how finely ground the progesterone powder is the type of base used the compounding skills of the pharmacist. 31 BHRT Study 189 women between the ages of 45 and 60 prescribed BHRT: all received progesterone and BiEst topically. Some also received testosterone, DHEA. 70% complained of ‘brain fog’ 55% complained of weight gain. 32 Study Results 90% completely or partially improved on symptoms of brain fog. 60% of women who gained weight, lost weight. Average weight loss was 14.8 pounds. 33 Cortisol Effects High levels of cortisol can compete with the other hormones, creating a ‘functional deficiency’ of hormones. Progesterone or testosterone in normal range, but the body functions as if there is not enough 34 Cortisol and DHEAS Cortisol is catabolic, meaning it breaks down muscle and bone DHEA is anabolic, meaning it builds up muscle and bone Balance becomes more catabolic with age as DHEA levels decline and cortisol levels increase 35 Adrenal Fatigue High cortisol levels over time cause damage, and the body slows cortisol release to prevent further damage. Decreased cortisol release leads to adrenal fatigue and inability to regulate other hormones. 36 Thyroid Thyroid issues more common as perimenopause is reached: higher overall estradiol levels in perimenopause reduced amount of free thyroid hormone. Too low or too high cortisol can also affect thyroid. 37 BHRT Summary Bio-identical hormone replacement (BHRT) is an accepted standard of hormone replacement, although there is controversy around custom compounded forms of BHRT Oral progesterone is accepted, and progesterone cream is gaining acceptance. BiEst and TriEst are still unproven therapies, but preferred by many women.