Bio-Identical Hormone Replacement Therapy (Bhrt)

4/2/2017

BIO-IDENTICAL HORMONE REPLACEMENT THERAPY (BHRT)

Erin Lucie, DNP, MSN, APRN, FNP-C CNS Pharmacology April 8th, 2017

Learning Objectives

At the conclusion of this activity, the participant will be able to: • Discuss the current research on BHRT • Discuss the basic pharmacology and physiology of the hormone endocrine system • Discuss the functions and relationships of estrogen, progesterone, testosterone, insulin, cortisol and DHEA • Describe the clinical applications and dosing of BHRT • Identify tools for prescribing BHRT • Describe the laboratory testing and monitoring of BHRT

Hormones

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Hormone Therapy Terminology • Natural: The term “natural” cannot be used to describe hormones or hormone therapies, because it lacks a unified definition: – “found in nature” or the substance was not man-made in a laboratory – End substance cannot be found in nature, however source materials used to create it can – or for scientific types, natural does not refer to the source of a substance, but that it is found naturally in the system to which it is being introduced • Synthetic: Synthetic is another term with a variable definition, depending on who is asked: – Any therapeutic agent produced by a drug manufacturer that does not contain exclusively bio-identical hormones – any therapeutic agent that is produced in a lab – any substance that is foreign to the body • Bio-Identical: Bio-identical means that the hormone has the exact same chemical structure as the endogenous hormone, and thus, it is indistinguishable from the hormone produced by the body

Physiologic balance

• Bio-identical hormone replacement therapy is restoring hormone levels in a patient to a balanced physiologic level mirroring that of a more youthful age. • PRIMARY APPROACH using nature and science to identify the deficiency/excess at the molecular level and correct it with bio- identical molecules. • Goals of BHRT are two fold: 1. Address symptoms of patient 2. Restore protective benefits the hormones offer

Non-bio-identical hormone derivative substitutions

Secondary Approach is with Pharmaceuticals which create a non- natural, patentable substance that will produce some improvement of symptoms: • Progesterone substitutes: medroxyprogesterone acetate (MPA- Provera) and other progestins

• Estradiol substitues: conjugated equine estrogens (CEE- Provera) and ethinyl estradiol (birth control pills)

• Testosterone substitue: oral methyltestosterone

• Horse hormones are bio-identical to horses but not humans.

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Establishing Need

Start with a comprehensive patient assessment 1. Hormone Health Evaluation 1. Medical History 2. Include immediate family major medical issues 3. Include lifestyle factors that may affect systems and/or influence the outcome of restoration therapy 4. Diet and exercise, caffeine, nicotine stressors 2. Patient symptoms 3. Testing

Tools • Androgen Deficiency in Aging Males (ADAM): questionnaire is an easy way to answer questions about your sexual health, which can help to see if you need your testosterone level checked.

• Female Sexual Function Index (FSFI):The FSFI is a brief questionnaire measure of sexual functioning in women. It was developed for the specific purpose of assessing domains of sexual functioning (e.g. sexual arousal, orgasm, satisfaction, pain) in clinical trials.

• Symptom chart with scale and/or calendar

Estrogen Symptoms Deficiency Dominance • hot flashes • breast swelling and tenderness • Sleep disturbance • sweet cravings • low libidio • nervousness • bone loss • mood swings • vaginal & bladder infections • PMS • night sweats • fibrocystic breasts • memory loss • weight gain (ab, hips, thighs) • headaches • anxiety • weight gain (waist) • fluid retention • heart palpitations • low thyroid symptoms • foggy thinking • uterine fibroids/cysts • painful intercourse • fatigue • depression • irritability • thin dry skin • heavy irregular menses • anxiety • headaches

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Progesterone Symptoms Deficiency Excess • symptoms of estrogen excess • exacerbates estrogen deficiency • swollen breasts due to down regulation of receptors • cramping • somnolence • depression • drowsiness • acne/oily skin • mild depression • irregular/excessive menses • gastrointestinal bloating • weight gain • breast swelling • anxiety • candida exacerbations • joint pain • PMS • infertility • brain fog • headaches

Testosterone Symptoms Deficiency Excess • prolonged fatigue • acne oily skin • muscle weakness • increased body hair • decreased libido • moodiness • depression • hirsutism • aches and pains • deepening of voice • memory lapse • scalp hair loss • heart palpitations • aggressiveness • vaginal dryness • clitoral enlargement • diminished feeling of well-being • insomnia • thin, non-elastic skin • anger • brain fog • agitation • bone loss • decreased HDL • incontinence • fluid retention • blunted motivation • infertility • fibromyalgia • increased insulin resistance

DHEA Symptoms Deficiency Excess

• decreased energy • Acne • difficulty dealing with stress • Increased facial / body hair • decreased immune function • insomnia • frequent infections • restless sleep • depression • hair loss • low libido • cardiac irregularities • dry skin and eyes • increased facial hair • muscle weakness • anger • weight gain • mild depression • loss of hair • irritability • irritability • sugar cravings • joint soreness • oily skin • rapid aging • headaches • anxiety • deepening of voice • fatigue • fatigue • weight gain • anxiety • elevated liver enzymes 12

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Cortisol Symptoms Low High • Cravings • Sleep disturbance • salt, stimulants • Low libido • high fat foods • hair loss • hypothyroid symptoms • elevated triglycerides • fatigue • bone loss • irritability • anxiety • irritability • memory loss • feelings of being overwhelmed • aches and pains • mental fatigue • weight gain -ab, waist • low progesterone /estrogen dominance • mild depression • allergies • inflammation • decreased stamina • wired but tired • emotional instability • binge eating • apathy • hypertension • chemical sensitivities • insuling resistance • poor memory • hyperglycemia • poor concentration • hyperlipidemia • lethargy 13

Hormones and Aging

• Estradiol declines at age 25 and disappears by age 50 • Progesterone declines at age 30 • Growth Hormone declines at age 25 by 14% every decade • DHEA and Testosterone decline at age 20 -50 by 50-80% • Cortisol increases with age and stress, then drops (adrenal fatigue) • Melatonin decreases with high glycemic index carbohydrates intake, alcohol, tobacco, caffeine, electromagnetic fields and benziodiazepines. Melatonin releases sex hormones, decreases cortisol, antioxidant, blocks estrogen receptor sites = cancer preventative •Insulin imbalance- diabetes and diet.

Menopause • Age 35-55 • Estrogen deficiency is “a state of accelerated aging”* • Progesterone deficiency • Testosterone deficiency

Combined deficiencies cause: • Irritability, insomnia, brain dysfunction • Alzheimers and dementia • Fatigue, aches and pains • Osteoporosis- fractures and loss of teeth • Genital atrophy and vaginal dryness • Atrophy of the skin and connective tissue • Heart disease • Breast Cancer and sore breasts • Cycling after age 55 increase risk of breast cancer

Birge, S., “The use of estrogen in older women,” Clin Geriatr Med 2003; 19(3):617 27.

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FUNCTIONS OF ESTROGEN Estrogen has over 400 functions in the body • stimulates choline acetyltransferase, an enzyme that prevents Alzheimers • increases metabolic rate • improves insulin sensitivity • regulates body temperature • prevents muscle damage • improves sleep and mood • reduces cataracts and glaucoma risk • maintains elastic arteries • dilates small arteries • inhibits platelet stickiness • decreases plaque on arteries • maintains memory • helps with fine motor skills • enhances production of nerve-growth factor • increases HDL 10-15% • reduces heart disease by 40-50% • maintains bone density • prevents tooth loss • decreases colon cancer risk

STUDIES

In a 2013 study: researchers estimated that over the past decade between 18,600 to 91,600 postmenopausal women, ages 50 - 59 years old, who had had a hysterectomy may have died prematurely because they did not take estrogen.

Sarrel, P., et al., “The mortality toll of estrogen avoidance: An analysis of excess deaths among hysterectomized women aged 50 to 59 years,” Amer Jour Public Health 2013; July 18.

A meta analysis from 27 published studies showed a 28% reduction in mortality in menopausal women under age 60 who used hormone replacement therapy and the participants also had improved quality of life.

Salpeter, S., et al., “Bayesian meta analysis of hormone therapy and mortality in younger postmenopausal women,” Amer Jour Med 2009; 22(11):1016 22.

Breast Cancer • Give female hormones, otherwise has more recurrence and mortality • Give lower amounts of estradiol and estriol and higher amounts of progesterone. • Never let your patients get sore breasts • Progestins increase the risk of breast cancer • 40% increased risk of developing breast cancer in women who used estrogen with progestin. • In women who used estrogen combined with progesterone there was a trend toward a decreased risk of developing breast cancer.

Rossouw, J., et al., “Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the Women’s Health Initiative randomized controlled trial,” JAMA 2002; 288(3):321 33.

Fournier, A., et al., “Breast cancer risk in relation to different types of hormone replacement therapy in the E3N EPIC cohort,” Int Jour Cancer 2005; 114(3):448 54.

Porsch, J., et al., “Estrogen progestin replacement therapy and breast cancer risk: the Women’s Health Study (U.S.),” Cancer Causes Control 2002; 13(9):847 54.

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Osteoporosis A hormone deficiency disease. Proper treatment?

• Estrogen prevents resorption of old bone while testosterone, progesterone and DHEA and GH build new bone. • BHRT increases bone density better then Fosamax and preserves normal bone remodeling (no rotting jaw, eye inflammation or decreased calcium • In 2004, the Surgeon General studied osteoporosis in the United States and wrote a report over 330 pages long on the best ways to promote bone health and prevent osteoporosis and fracture. His advice, in essence, is to work with nature.

Office of the Surgeon General (US). Bone Health and Osteoporosis: A Report of the Surgeon General. Rockville (MD): Office of the Surgeon General (US); 2004. Available from: https://www.ncbi.nlm.nih.gov/books/NBK45513/

Functions of Progesterone

• The principal target organs of progesterone are the uterus, the breasts, and the brain.

• Progesterone has an anti estrogenic effect on the myometrial cells, decreasing their excitability, their sensitivity to oxytocin, and their spontaneous electrical activity while increasing their membrane potential.

• Progesterone down regulates the number of estrogen receptors in the endometrium and increases the rate of conversion of 17 estradiol to less active estrogens.

• Large doses of progesterone inhibits LH secretion and potentiate the inhibitory effect of estrogens, preventing ovulation.

• Progesterone is thermogenic and may be responsible for the rise in basal body temperature at the time of ovulation.

• Large doses of progesterone produces natriuresis by blocking the action of aldosterone in the kidney. 20

Functions of DHEA

• Decreases cholesterol • Lowers triglycerides • Prevents blood clots • Increases bone growth • Promotes weight loss • Increases brain function • Increases lean body mass • Increases sense of well being • Helps one deal with stress • Supports the immune system • Helps the body repair itself and maintain tissues • Decreases allergic reactions

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Functions of Cortisol • Balances blood sugar • Mood and thoughts • Weight control • Influences testosterone/estrogen ratio • Immune system response • Influences DHEA/insulin ratio • Bone turnover rate • Affects pituitary/thyroid/adrenal system • Stress reaction • Participates with aldosterone in sodium • Sleep reabsorption • Protein synthesis • Is an anti inflammatory

22 Image courtesy Erin Lucie (2017)

Functions of Insulin • Counters the actions of adrenaline and cortisol in the body • Helps the body repair • Helps convert blood sugar into triglycerides • Keeps blood glucose levels from elevating • Plays a major role in the production of serotonin • At normal levels increases development of muscle Insulin and Sex Hormone Relationships: • Estrogen,progesterone,DHEA,and thyroid hormones are all important for the regulation of glucose in the body • Estrogen lowers blood sugar in a women • Testosterone decreases blood glucose in a male • Progesterone raises blood sugar if not balanced with estrogen Low levels: This is a pre diabetes state. Symptoms include bone loss, fatigue, depression and insomnia.

Excess: Acne. Accelerates aging process. Diabetes and insulin resistance. Insomnia. Asthma, breast cancer risk, colon cancer, heart disease, hypertension, hyperlipidemia and osteoporosis.

Sex Hormone Binding Globulin SHBG

• SHBG is a carrier protein for testosterone and DHT and E2 • If SHBG is high then there is less E2 and testosterone available for use by the body. • If SHBG is low, more estrogen and testosterone are available for usage. • Low SHBG may be a marker for low thyroid function. • High insulin levels are a negative modifier for SHBG as are high prolactin levels • Estrogen by mouth increases SHBG by 50% • CEE (conjugated equine estrogen) increases SHBG by 100% • Transdermally applied estrogen minimally increases SHBG unless there is an overdose

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Testosterone in Men Andropause Testosterone replacement • Testosterone levels decline in Men • Dilates coronary arteries and • Fatigue, reduced mental function • Passivity and moodiness improves angina • Loss of drive and ambition • Increase heart muscle size • Loss of muscle mass, increased abdominal fat and strength • Loss of Libido, no morning erections • Decreases fibrinogen levels- • Increased risk of heart disease prevent blood clots • Increased risk of prostate disease • Increase risk of Alzheimer's • No increase in prostate • Increase risk of autoimmune disease cancer!

Testosterone replacement therapy for men is safe and can provide significant benefits. Uncontrolled and controlled trials date back over 70 years. There is not a reported age at which hormone replacement in men over the age of 50 should not be considered. - Pam Smith

Estrogen Dominance In Men

• Estrogen dominance is a probable cause of prostate enlargement and possible cause of prostate cancer • Elevated estrogen/Test ratios in BPH • High levels of estradiol and estrone found in BPH tissues • Alcoholics may have high estrogen levels • Low fat, Vegetarian diets, and if low in protein, can increase SHBG which lowers free testosterone. • Also men on low-fat, high-fiber, vegetarian diets were shown to have lower total and free testosterone which was reversed when they went back on their regular, high protein, diet.

th Allan, C., et al., Androgen Deficiency Disorders. In DeGroot, L., Jameson, J., (Eds.) Endocrinology. 5 Ed. Philadelphia: Elsevier, 2006, p. 3159-91.

Symptom Evaluation • Symptoms of different hormone imbalances can overlap. • Symptoms of excess of any hormone can reflect symptoms of deficiency of that hormone. • Symptoms of excess estrogen or excess progesterone or high cortisol can mimic symptoms of estrogen deficiency. • Low thyroid and/or poor nutrition look like low testosterone. • High cortisol looks like low testosterone, high estrogen and low progesterone. • You can not go by symptoms alone! Use your labs for therapeutic levels, but do keep track of symptoms; How many and when? i.e. hot-flashes and headaches • Too much estrogen will cause a delayed down regulation of receptors- your mind shuts them off. • Dose to the patients symptoms not the labs- but know the possible cause of the symptoms. • Look at the groups and correlate with levels.

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The Steroid Hormone Cascade

• Sterol: • a subgroup of the steroids and an important class of organic molecules. • Occur naturally in plants, animals, and fungi, with the most familiar type of animal sterol being cholesterol. • Cholesterol: • vital to animal cell membrane structure and function as a precursor to fat soluble vitamins and steroid hormones.

• All steroid hormones are chemically synthesized from diosgenin (Mexican wild yams, soy and plants).

Image courtesy of ZRT labs: https://www.zrtlab.com/images/documents/Steroid_Hormone_Cascade.pdf

Measurement of Hormones

• Saliva • Urine • Blood – Capillary blood spot – Venous

CONCLUSIONS: Pharmacologic dosing of hormones, as evidenced by laboratory levels on therapy, is needed to produce a physiologic effect in patients. However, safety, tolerability and clinical response should guide therapy rather than a single measurement, which is extremely variable and inherently unreliable.

NORMAL RANGES OF LABS VS. OPTIMAL RANGES 29

Monitoring of hormones Frequency • Baseline levels on all patients • Follow-up 3-4 months after initiation of therapy • As needed per patient symptoms • Monitoring annually or at providers discretion Timing • Avoid peaks and troughs • Test sample at midpoint of dosing • Testosterone and Cortisol highest before 10am • Male or menopause: before 10am any day • Pre/peri-menopause day:18-21 • Fertility: day 3 (FSH,E2) & day 19 (P, E2,DHEA,Cortisol, Folic acid, Vit. D, Insulin • Cortisol: 4 times a day on 1 normal stress day Minimum hormone testing • Females: Estradiol, Progesterone, DHEA, testosterone and cortisol x 4. • Add Estrone and Estriol once on any hormone therapy • Male: Estradiol, Testosterone, DHEA, PSA, SHBG and Cortisol x4 • if hypothyroid symptoms add: TT4, fT4, fT3, TSH, TPO, Vit D and ferritin 30

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Dosing Principles

• Goal should be to use the lowest amount of hormone required to achieve physiological level and control symptoms • Be conservative: dose low and go slow • Especially estrogen- any increase in estrogen is going to increase a estrogen metabolite= increase in cancer risk.

WHY DO WE GET SIDE EFFECTS?

1. Inappropriate route of administration • Oral estrogen 2. Excess dose 3. Imbalance with other hormones • Estrogen without progesterone (even with hysterectomy)

Healthy Male Daily Hormone Production • Cortisol 20-30mg • Estrone 0.066mg • Testosterone 5-6mg • Estradiol 0.045mg • Androstenedione 3mg • DHEAS 50mg • DHT 0.3mg • DHEA 15mg

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Optimal Receptor Response

Salivary Estradiol levels & Hot Flashes of 49,000 women

number of hot- flashes

Amount of estradiol given

Chart adapted from: Jim Paoletti (2015)

Administration Considerations

• Oral: first pass effect in liver • Vaginal: excellent absorption. Inconvenient. • Suppository • Cream • Gel • Transdermal: static or pulsitility with bimmemetric • Sublingual • Troche • Drops • IM injections: 1-4 weeks. Peaks & troughs. • SQ injections: injection site reactions • Pellet: E2 and T only. Last 3-6 months. Surgery, infection.

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Appropriate Routes of Bi-identical Hormones

• Estradiol: Transdermal, vaginal, then injectable. Rarely oral. • Progesterone: Vaginal. Insomnia consider oral. • Testosterone: Topical then IM injectable. No oral. • DHEA: Oral • HGH: SQ then SL • Desmopressin: oral, 2nd line nasal or injectable • Hydrocortisone: Oral. Transdermal causes skin atrophy. • Oxytocin: SL or nasal • Melatonin: Oral • Vitamin D: Oral then IM injection

Dangers of Estrogen Estrogen Oral Estrogen Alone • First pass effect on the liver- • Synthetic hormone therapy and Decreases IGF-1, Increases SHBG, OCPs reduce DHEA and Increases CRP, Increases clotting Testosterone by 25-60% factors: blood clots, strokes and • heart attacks Estrogen without progesterone and testosterone = estrogen • Even at 1/10 of the smallest dose available increase risk dominance and increase risk of breast cancer • Smokers have an even greater risk • CEE increases clotting much more than estradiol, premarin. • Transdermal and vaginal estradiol does NOT do this.

Dangers of Progestins

Provera Bio-Identical Progesterone • Causes birth defects • Maintains pregnancy • Depression • Improves sleep • Insomnia, irritability • Diuretic • Fluid retention • Lowers blood sugar • Raises blood sugar • Maintains estrogen-induced • Counteracts estrogen-induced arterial dilation arterial dilation • Worsens lipid profile • Improved lipid profile • Causes heart attacks • No evidence of CVD • Increases estrogenic stimulation • Reduces estrogenic stimulation of breasts of breasts • Causes breast cancer • Prevents Breast Cancer

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Estrogen and Progesterone Complementary system Estrogen Progesterone• Progesterone stops proliferation and • Estrogen promotes breast and promotes maturation and uterine tissue proliferation and differentiation growth • differentiation cells CAN NOT become cancer

• Breast, uterine and ovarian tissues undergo a monthly cycle of proliferation, differentiation and breakdown. • Defects in this cycle can lead to cancers: bi-mmmetrect • Cycling increase risk of estrogen dominance • Historically women usually: pregnant (high progesterone) or Breastfeeding (low estrogen) – both breast cancer protective. Women started cycling at age 17. Cycled for 4 years average • Today start as young as age 9 and cycle for 35 years. • With aging, fewer oocytes of lower quality are left reduces progesterone and creates estrogen dominance • Estrogen swings from very high to very low for several years. • High average progesterone/estrogen ratio suppresses proliferation and prevents cancers in famles.

Contraceptive Considerations

Conventional OCP have risks • 2x risk of stroke, heart attack • 2-30x risk of blood clots • 1-3x risk of breast cancer • Increased blood sugar, blood pressure • 1.5x risk systemic Lupus erythmatosis • Liver tumors

Instead use • Bio-Identical birth control protocol • Diagnosis and fix the hormonal imbalance

• Use copper IUD, condoms, ablation, tubal, etc… 41

Converting from conventional hormone derivatives to BHRT 1. Stop synthetic progestins immediately and replace with progesterone simultaneously 2. Always taper down estrogen dose before switching to bi-est (estradiol and estriol) Sample Schedule • Start progesterone • Prescribe CEE 0.625mg and CEE 0.3mg • Week 1-2: 0.625mg 2 of 3 days, 0.3mg every 3rd day • Week 3-4: 0.625mg 1 of 3 days, 0.3mg 2 of 3 days • Week 5-6: 0.3mg daily • Week 7-8: 0.3mg 2 of 3 days, nothing on 3rd day • Week 9-10: 0.3mg every other day • Week 11-12: change to topical bi-est once taper completed • bi-est 50:50 low dose- 0.05mg to 0.25mg

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Physiologic Doing Guidelines for Females

Condition Hormone Route Dosage Dosing Days given Notes Range PMS Progesterone Oral SR 25-100mg 1-2 x day cyclically day 14-25 Topical 5-20mg 1-2 x day cyclically day 14-25 Peri- Progesterone Oral SR 25-200mg 1-2 x day cyclically menopasue day 14-25 Topical 5-50mg 1-2 x day cyclically day 14-25 Bi-estrogen Topical 0.05-0.20mg 1-2 x day days 1-25 take with an above (50:50) progesterone Testosterone SL 0.5-4mg Q am

Topical 0.25-2mg Q am

DHEA Oral SR 5-20mg Q am optional

Topical 0.5-2.5mg Q am optional

Physiologic Doing Guidelines for Females

Condition Hormone Route Dosage Range Dosing Days given Notes Menopause Progesterone Oral SR 25-400mg 1-2 x day continous

Topical 10–50mg 1-2 x day 6 days a week

Bi-estrogen Topical 0.05-0.25mg 1-2 x day continous 6 days a week. (50:50) “holiday” No oral! Testosterone SL 0.5-4mg Q am

Topical 0.25-2mg Q am

DHEA Oral SR 5-20mg Q am optional

Topical 0.5-2.5mg Q am optional

Cancer Risk Estriol Topical 0.1-2mg 1-2 x day continous titrate up Vaginal 44

Physiologic Doing Guidelines for Males

Hormone Route Dosage Range Dosing Notes Testosterone SL 2.5 -20 2 -3 x day Do not swallow! nasal Topical 1-20mg Q am Rub well. Wash hands. Don’t transfer. IM injection 50-100mg Weekly Cypionate Pellets 800-1200mg q 3-6 months Progesterone Oral SR 5-10mg Q hs Topical 0.25–2.5mg Q hs Rub well. Wash hands. Don’t transfer. DHEA Oral SR 5-25mg Q am Topical 1-10mg Q am HCG SQ 125-250iu Q 3-7 days Testicular artophy Arimidex oral 0.5- 1mg Half tab 2-3 x a Aromatase inhibitor if week Estradiol >35. Chrysin oral 500-1500mg daily Aromatase inhibitor if Estradiol >35. topical 30-50mg daily 45

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Customs Compounding Post-Menopause • Hormone replacement therapy is needed to maintain vital functions such as cardiovascular, liver, bone, brain, skin, etc., even when the patient is asymptomatic as far as the typical symptoms of menopause • Use lower doses if the patient is asymptomatic • May use cyclically and continue a natural menstrual cycle

Vaginal Atrophy Hyaluronic Acid 5mg/gm Compound Vaginal Cream Estriol 5mg/ml Vaginal Cream Dehydroepiandrosterone 13mg Suppository (DHEA) Estriol 1mg/Progesterone 30mg Suppository

Female Sexual Dysfunction/Libido Testosterone1%TopicalCream Aminophylline 3%/Arginine HCl 6% Topical Gel Oxytocin40units/gmVaginalCream

Vaginal Dryness Estriol 0.1%/Testosterone 0.1% Vaginal Gel Vitamin E 200iu/gm Vaginal Gel 46

Polycystic Ovarian Syndrome

Low progesterone caused by irregular ovulation FSH/LH inbalance, why? Developing Insulin Resistance. Why? Poor diet, inadequate exercise and improper sleep habits. You must address underlying lifestyle issues. If these are not corrected, then the cause of the problems are not being addressed. At risk for additional hormonal imbalances and complications.

Treatment • Lifestyle modifications (ketogenic diet and High Intensity Interval Training) • Metformin HCl 10% Topical • Spironolactone 5% Topical Cream • Progesterone supplementation cyclical and bimmetric • Inositol • natural anti-inflammatories

Transgender Considerations

• Must have referral letter for medical necessity from psychology before initiation of hormones • Hormone supplementation for patients who are physically transitioning hormonally from one gender to another is different from other types of hormone replacement. For example, when we decide on hormone treatment with menopausal patients, we usually use low and physiological dosing. However, when we are helping transition a patient hormonally, we must use much higher dosages. • Dose to upper levels of normal of physiologic levels of identified gender

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Do’s and Don’ts Pearls

• Never (hardly ever) give oral estrogen! Why risk it? • Do always provide with progesterone with estrogen for brain, breast and uterus • Do check HMG/HCT every 3 months if on testosterone. Erythrocytosis = therapeutic blood donation! • Do find and befriend a compounding pharmacist and Pharmacy • Do not stop progesterone if pregnant= miscarriage • Never let your patient have breast pain • Thyroid and GH: need to correct the cortisol deficiency (intolerance) first • GH increases thyroid = decrease your dose • GH decreases cortisol = increase your cortisol • With Cortisol: always provide DHEA, in a 1:1 ratio i.e. 20mg cortisol + 20mg DHEA

Summary

• Get baseline laboratory levels and symptoms. • If a hormone is missing, replace it. • If a hormone is insufficient, enhance it. • Recheck levels and adjust until optimized. • Hormone restoration makes you feel better and improves your health.

Summary

• The symptoms of hormone loss are the warning signs of physical deterioration. • There can be deficiencies at any age, don’t wait! • All hormones are designed to work harmoniously together, • If one is altered, excess to deficient, it will affect the actions of the other hormones. Keep your charts handy! • Bio-identical, compounded, customized hormone replacement is the only way to achieve this balance. • One size does not fit all. There is no app for that! We must evolving our best practices for optimal patient outcomes

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Want to learn more about Hormone restoration and compounding

A4M The American Academy of Anti-Aging Medicine

PCCA Professional Compounding Centers in America

email me for questions: [email protected]

References

th Allan, C., et al., Androgen Deficiency Disorders. In DeGroot, L., Jameson, J., (Eds.) Endocrinology. 5 Ed. Philadelphia: Elsevier, 2006, p. 3159-91.

Birge, S., “The use of estrogen in older women,” Clin Geriatr Med 2003; 19(3):617 27.

Bubenik, G., et al., “Melatonin and aging: prospects for human treatment,” Jour Physiol Pharmacol 2011; 62(1):13 9.

Fournier, A., et al., “Breast cancer risk in relation to different types of hormone replacement therapy in the E3N EPIC cohort,” Int Jour Cancer 2005; 114(3):448 54.

Mohamed, O., Freundlich, R. E., Dakik, H. K., Grober, E. D., Najari, B., Lipshultz, L. I., & Khera, M. (2010). The quantitative ADAM questionnaire: a new tool in quantifying the severity of hypogonadism. International Journal of Impotence Research, 22(1), 20–24. http://doi.org/10.1038/ijir.2009.35

Pandi Perumal, S., et al., “Melatonin antioxidative defense: therapeutical implications for aging and neurodegenerative processes,” Neurotox Res 2013; 23(3):267 300.

Paoletti, J. (2015). A practitioner guide to physiologic bioidentical hormone balance. Grove City, OH. Paoletti Publishing. ISBN:978-63337-037-1

Porsch, J., et al., “Estrogen progestin replacement therapy and breast cancer risk: the Women’s Health Study (U.S.),” Cancer Causes Control 2002; 13(9):847 54

Smith, P. (2008). What you must know about women's hormones. Garden City Park, NY. Square One Publishers