 1 Clinical Application of BHRT Tracy Marsden BScPharm, DHPh

2 Types of Hormones  Estrogens  Progesterone  Testosterone  Cortisol & DHEA

3 Pre-Menopause OVARY Testosterone Estradiol Estrone Estriol Progesterone aromatase

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 Testosterone Estradiol Estrone Estriol Cortisol Dehydroepiandrosterone (DHEA) Androstenedione aromatase

9 Normal Cycles  Progesterone is produced in quantity after ovulation

Relative excess of estrogens over progesterone. Cycles are irregular. Progesterone peaks after ovulation and balances estrogens. Cycles are regular. Very little progesterone or estrogens released by ovaries. No cycles. Menstrual Cycle – 6 month view Peri-menopause – 6 month view Post-menopause – 6 month view

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 bio- identical hormones

14 Step 1: Symptom Assessment  Hot flashes  Memory lapses  Night sweats  Foggy thinking  Water retention  Heart palpitations  Breast tenderness  Irritability  Decreased sex drive  Loss of muscle bulk 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’:  Allergies. If you do not understand the symptom, please leave circles blank. Symptom Assessment

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 bio- identical 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  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.  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. Progesterone MPA

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.