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11/11/2015 Jill Earl CNM,CRNP Calm Your Hormones! OR EVERYTHING YOU SHOULD KNOW ABOUT HORMONE THERAPIES Hormone Production &Utilization LITTLE PACKAGES WITH A BIG IMPACT Key Components of Overall Health Chemical substances produced in the body that control and regulate the activity of certain cells or organs. They are powerful molecules They interact with each other. They can interact with the cells on the surface at receptor sites OR Enter directly into the cell and interact inside the nucleus The action can be direct or indirect The interface and result can be a single direction, or can form a cascade of action Women’s Health • Your sex hormones interact with cortisol (stress hormone) and insulin (glucose regulator) • They are made by pregnenolone, the memory hormone • They interact with thyroid hormones (metabolism) • Hormone levels influence each other and change over time • Environment, diet, toxins and life stage are all factors 1 11/11/2015 A few good hormones ALSO KNOWN AS THE SEX HORMONES Estrogen • • • Estrone (E1) Estradiol (E2) Estriol (E3) Progesterone Testosterone • stor Estrogen NAMED FOR THE OESTRUS CYCLE • The primary female sex hormone • Develops secondary sex characteristics breast development thickens endometrium part of cycle regulation • FSH and LH regulate the production in ovulating women • Circulating estrogen will decrease FSH and LH • Presence in the first 14d of cycle inhibits ovulation Estrogen con’t • Produced primarily in the ovaries, corpus luteum and placenta • All three estrogens are produced from androgens through enzyme action • E2 produced from testosterone and • E1produced from androstenedione • Androstenedione is made in the theca interna cells (in the ovary) from cholesterol • Your body has receptor sites everywhere! • There are more than 400 known functions 2 11/11/2015 Low estrogen levels • Smokers • Low Fat Diets • Common symptoms: Acne Anxiety Arthritis decrease in libido infertility Chronic fatigue Decrease in memory Depression panic attacks vulvodynia PCOS thinner skin palpitations vaginal dryness osteoporosis/osteopenia incontinence Thin endometrial stripe High estrogen ESTROGEN EXCESS / ESTROGEN DOMINANCE • Includes most women with estrogen imbalance • Over production of estrogen • Progesterone/estrogen ratio imbalance • Xenoestrogens(environmental bombardment) • Common symptoms: bloating fatigue cervical dysplasia heavy periods panic attacks ESTRONE decreased libido hypothyroidism insomnia mood swings fibroids edema headaches irritability weight gain (E1) Derived from E2 Main estrogen post menopause Reserve source of estrogen Converted to E2 in ovaries Routine alcohol consumption increases ovarian E1 3 11/11/2015 ESTRADIOL (E2) Strongest form of estrogen Main estrogen in the body before menopause Mostly made in the ovaries High levels associated with increased risk of breast & uterine cancer ESTRIOL (E3) Less stimulating to breast & uterine lining Does not promote breast cancer It is an adaptogen, adapting to the specific environment Does not protect bone, heart or brain like E2 Does help bone a little and ↓ cholesterol There are two types of receptors ER ALPHA AND ER BETA • ERα increases cell growth, proliferation • ERβ decreases cell growth, helps prevent breast cancer • E2 equally activates both receptors • E1 activates ERα selectively 5:1 • E3 activates ERβ selectively 3:1 • E3 has 20-30% affinity for ERs compared to E2, therefore cleared rapidly from the cell • E3 at concentration is equivalent to E2 4 11/11/2015 ERα and ERβ con’t • Receptors ERα and ERβ are similar and respond in comparable ways. • Phytoestrogens have a greater affinity to ERβ. The regulatory domains differ between the receptors and is beyond the scope of this talk. Synthetic estrogen MOST COMMONLY RX’D HT IN THE USA Premarin is a mixture of estrone, sodium equilin sulfate, and components such as 17-alphadihydroequilin,17 alpha-estradiol, and 17 beta-dihydroequilin. Equilin and equilenin are horse estrogens. There are other additives and coatings. Synthetic estrogens contain many estrogens that do not fit into human receptors, and it is unknown what happens to them. Synthetic estrogen CON’T The estradiol your body makes is eliminated from your body through urine within a day. Equilin, derived from the urine of horses, has been shown to persist in the body for 13 weeks. Human enzymes are designed to metabolize human estrogen, not horse’s. 5 11/11/2015 On to Progesterone! BEST KNOWN AS THE PREGNANCY HORMONE Important in menstruation, pregnancy and the formation of embryos. Made in the ovaries until menopause. Performs many functions in the body! Balances estrogen helps sleep Helps build bone prevents anxiety Helps bladder function Relaxes smooth muscle in the gut and blood vessels Signs of progesterone imbalance YOU CAN HAVE TOO MUCH OR TOO LITTLE • High P4 • Only happens if taking too much or too much pregnenolone • leaky bladder • ligaments relax • backaches • Leg aches • hip pain Progesterone deficiency • Many causes: low LH increased saturated fats stress high sugar intake decreased thyroid hormone 6 11/11/2015 Synthetic progesterone PROGESTIN • Does not have the same structure as the body makes • Does not reproduce actipons of ‘natural’ progesterone does not balance estrogen interferes with body’s production of progesterone • Attaches to multiple receptor sites, nopt just PR • Stops the protective effects estrogen has on heart and causes spasms of arteries Synthetic P4 CON’T • Studies have shown progestin increase risk of breast CA by 800% when compared to estrogen alone • An article in JAMA discussed the risk of developing breast CA was predicted to rise by 80% after 10 yr of using estrogen &/or progestin • Cardiologist Stephen Sinatra MD,FACC has found progestins cause cardiac SEs including SOB, fatigue, chest pain and HTN “Menopausal estrogen-progestin replacement treatment and breast cancer risk” JAMA, 2000;283:485-491 progestin THE GOOD, THE BAD The good: does help build bone helps thyroid function protects against fibrocystic disease normalizes zinc and copper levels proects the uterus from cancer The bad: acne increased appetite and wt gain depression hair loss decreased libido increased LDL breast tenderness 7 11/11/2015 Natural progesterone • Same chemical structure as the body makes • Made from yams or soy • Disogenin, a plant steroid, can be turned into an exact duplicate of human progesterone • Has all the important good effects of progesterone and no serious SEs. • Most common SEs: – Dizziness – Fatigue – nausea Effects of Progesterone • Balances estrogen & fluids in cells • Decreases rate of cancer on all PR • Does not change the good effects of estrogen on blood flow • Enhances thyroid • Calming • Cycle regulation • Messages body to maintain conception More good stuff PROGESTERONE RULES! • • • • • • • • • Short half life Lowers BP, relaxes smpooth muscle Normalizes/improves libido Natural antidepressant Increases metabolic rate & scalp hair as well Anti-inflammatory Prevents menstrual migraines Promotes myelination and protects nerves from injury Lowers cholesterol 8 11/11/2015 Natural progesterone DOSING TIDBITS… Can be taken orally or transdermal SL is a form of transdermal For insomnia take the oral Prometrium is micronized in a base of peanut oil Absorption rate for oral increases with age Adrenaline blocks progesterone receptors Transdermal progesterone • Hormones are all lipophilic • Subcu receptors get loaded over time, so rotate sites • If commercial cream, not compounded, be sure label says USP progesterone or it may lack enzyme for conversion • If exact dosing is required, do SL or injectible Testosterone THE MASCULINE HORMONE • An androgen, usually seen as the male hormone b/c it stimulates male secondary sex characteristic • Estrogen stands in opposition- a balancing act • Made in the adrenal glands and ovaries • Production decreases with age • Only 1% of circulating testosterone is free and bioavailable, the rest is bound to SHBG 9 11/11/2015 testosterone CON’T • Inhibits bone catabolism • Decreases body fat, increases muscle mass • Increases libido • Elevates norepinephrine in the brain Testosterone imbalance • Androgen dominance is the most common hormonal disorder in women • PCOS • Signs and symptoms: anger agitation insulin resistance fluid retention hirsutism infertility irregular menses Testing and Dosing SOME QUICK FACTS • Serum progesterone WNL: before ovulating/after menopause – 1ng/ml mid cycle- 5-20ng/ml pregnant- 1st 11.2-90 ng.ml 2nd 25.6-89.4 3rd 48.4-42.5 10 11/11/2015 Estrogen levels (E2) • • • • During menses 45 ng/ml Ovulation peaks near 400pg.ml Pregnancy- up to 100x higher After menopause 10-20 pg/ml (optimal is 40-50 pg/ml) Testosterone levels • Females 12-16 yr • 19 yr+ <7-75 ng/ml 8-60 ng/ml • Average adult male 270-1,070 ng/ml • Average adult female 15-70 ng/ml Dosing QUICK AND DIRTY…. Remember dosing can be ‘usual amounts’ but will always be evaluated individually in the patient ! Bioidentical preparations are compounded by the compounding pharmacist according to your orders. These can be shipped to patient. 11 11/11/2015 Beginning dosages for common problems: • Menstrual migraines d 22-25 • Endometriosis rec’d salivary testing to determine E2 dominance Progesterone 200mg-400mg ½ troche BID Menopause Syndrome Biest 1-2mg/Progesterone 200mg ½ troche SL BID daily or cyclic • PPD • PP insomnia Progesterone 400mg SL daily Fibroids progesterone 200mg qd or cyclic PCOS progesterone 200mg ½ troche BID cyclic • Premature Ovarian Decline • Premature Ovarian Failure No menses, FSH >20 mlU/ml Needs Biest 0.5mg/Progesterone 200mg cyclic +heat + TCM herbs Many women can achieve menstruation and ovulation 12 11/11/2015 • Luteal phase infertility progesterone 200mg ½ troche SL BID on day 14-28 of cycle Patient should have been monitoring ovulation to insure correct timing The 3 P’s • PCOS metformin progesterone 200mg ½ troche SL BID cyclic • PMDD usually progesterone 200-400mg SL qd or cyclic day 12-24 Look at testosterone levels and estrogen levels, can be low • PMS progesterone 200mg troche ½ SL BID d 12-24 of cycle A little more about PMS SOME WOMEN HAVE LOW E2, NORMAL P4 • If the progesterone is not effect give phytoestrogens and/or herbs: Angelical sinensis (Dong Quai) Borage oil EPO Ginko Black Cohosh Vitex agnus castus 13 11/11/2015 A few good resources Clinical Gynecologic Endocrinology and Infertility 2010 by Marc A. Fritz MD and Leon Speroff MD What You Must Know About Women’s Hormones By Pamela W Smith, MD,MPH http://discovery.lifemapsc.com/library/review-of-medicalembryology http://e.hormone.tulane.edu/learning/estrogens.html Thank you for attending! Any Questions? My contact info: [email protected] Wellspan Family Health Georgetown (717)806-3800 14