Understanding & Co-managing Your Patients on Pellet Therapy Jennifer S. Hayes, DO,FACOOG

1. Understanding & Co-managingYour Patients on Pellet TherapyJennifer S. Hayes, DO,FACOOG

2. Menopause • Time in a woman’s life when she stops having monthly periods • The ovaries stop releasing eggs and stop making estrogen, progesterone and testosterone • Average age 51 • 95% 45-55 years of age

3. Estrogen • Present in Both Men and Women • Large Amounts in Women, Very Small in Men • Has OVER 400 Functions in the Body • Control Hot Flashes • Maintain Bone Density • Helps Maintain Memory • Maintains Collagen in Your Skin • Increases Serotonin and Dopamine (“Happy” Hormones in Brain)

4. Testosterone Provides major symptom relief AND protects the BONES, BRAIN, BREAST, HEART, & RELATIONSHIPS! • Present in both men and women • Large amounts in men --- smaller amounts in women • Men age 30-70 will lose 1-3% production per year • Women age 20-40 lose up to 50% per year!

5. Progesterone in Menopause • Progesterone is produced primarily by the ovary – therefore menopausal levels are ZERO • Progesterone drops even more drastically in menopause than estrogen does due to the limited areas of production • Important role balancing & opposing estradiol in the endometrium.

6. Facts About Menopause • 3500 women enter menopause daily • Symptoms may begin up to 10-15 years earlier • Most women are affected in more ways than they realize • Most women do not ever “get over” or “get through” menopause completely where they are completely asymptomatic

7. Peri-menopause Menopausal transition Lasts 4 – 10 years Marked by menstrual cycle changes Menstrual cycle may occur more or less frequently, may skip a menstrual cycle Bleeding may be lighter Symptoms of menopause such as hot flashes

8. Facts About Andropause • Male menopause or “MANopause” • 20% of males over 50 have low testosterone • Common in men with diabetes, high BP, sleep apnea & other chronic disease • Linked to early heart disease • Underdiagnosed

9. Do your patients feelLike This?

10. Or Like This?

11. THE MENOPAUSE HIT LIST • ExtremeFatigue • 3-4pm hit a wall? • Mood Swings • Anxiety • Tension & Irritability • Lack of Sleep • 3-4 am wake up? • Memory Loss • Depression • Lack of Focus • Brain Fog • Hot Flashes • Night Sweats • Weight Gain • Joint Pain • Bladder Symptoms • Decreased Sex Drive and/or Performance • Vaginal dryness • Painful Sex

12. Testosterone Deficiency • Loss of energy • Loss of mental clarity • Loss of muscle mass • Weight gain • Decreased exercisetolerance • Increased recovery time from exercise • Anxiety • Irritability • Bone loss • Decreased libido • Loss of erectile ability • Clitoral insensitivity or orgasmic dysfunction

13. Recent History of Traditional ERT • Estrone sulfate isolated from urine of pregnant mares in 1930s at University of Toronto • Premarin (CEE) first marketed in 1941 in Canada and in 1942 in US • Significant increase in endometrial CA noted in North America in years 1960 - 1975 • Progestin therapy (continued & combined cyclic) • Early 1980s, rate of endometrial CA returned to prior levels and remain steady • WHI published 20002 (NIH study) • Sales of CEE declined from $2B to $1B per year

14. Medical Studies NURSES HEALTH STUDY • 121,700 Nurses • Conjugated Estrogens Increase Risk of Breast Cancer RR 1.32 (1.14-1.54) • Estrogen PLUS Testosterone No Increase Risk of Breast Cancer RR 1.64 ( 0.53-5.00) Colditz NEJM 1995

15. Archives of Internal Medicine • Oral, Synthetic, Chemical Methyl Testosterone Increased the Risk of Breast Cancer • Estratest, Estratest HS, Syntest & Syntest DS • Non-Oral, Testosterone (Hormone) Prevents the Stimulation of Breast Tissue

16. The Nurses Heath Study – 121,000 women Younger cohort. 30-55 yr olds 1976-1995-2010-ongoing all different OC & HRT hormone mixes from 1970s to 1990s The WHI 2002 – 16,000 women Older cohort. 50-79 yrolds Premarin & Provera vs Premarin aloneNo large studies of Bioidentical hormones yet. Many small studies support the safety of Natural Estradiol, Natural Testosterone & Natural Progesterone – All while allowing more Quality of Life.

17. NAMS 2017 Position Statement THE NEW POSITION STATEMENT EXPANDS ON AREAS OF CONFUSION REGARDING HT – HT should be individualized for each patient and require periodic reevaluation for risks and benefits of selected therapy. – For women <60 years old or who are within 10 years of menopause onset and have no contraindications to HT, there is favorable benefit-risk ratio for HT treatments of hot flashes and for those at elevated risk for bone loss or fracture. Menopause: The Journal of The North American Menopause Society, Vol. 25 No. 7, pp. 728-753, 2017

18. NAMS 2017 Position Statement • For patients who initiate HT more than 10 or 20 years from menopause onset or who initiate when >60 years, the benefit-risk ratio is less favorable, considering the greater absolute risks for coronary heart disease, stroke, venous thromboembolism and dementia in these patient populations. • On continuation of therapy, HT does not need to routinely discontinued in women >60 or 65 years old. Menopause: The Journal of The North American Menopause Society, Vol. 25 No. 7, pp. 728-753, 2017

19. Society position statements THE AMERICAN COLLEGE OF OBSTETRICS AND GYNECOLOGY (ACOG) [4] – “Recent analysis suggest that HT may not increase CHD risk for select population of women who have experienced menopause recently…Some women may require extended therapy because of persistent symptoms.” THE EUROPEAN MENOPAUSE AND ANDROPAUSE SOCIETY (EMAS) [3] – “The main indication for HRT use in postmenopausal women remains the relief of menopausal symptoms…Treatment significantly decreases bone loss and risk of osteoporotic fractures…In 50- to 59-year old women a window of opportunity for a benefit in cardiovascular disease displays a high plausibility.” THE NORTH AMERICAN MENOPAUSE SOCIETY (NAMS) [2] – “Recent data support the initiation of HT around the time of menopause to treat menopause-related symptoms; to treat or reduce the risk of certain disorders, such as osteoporosis or fractures in select postmenopausal women; or both. The benefit-risk ratio for menopausal HT is favorable close to menopause but decreases with aging and with time since menopause in previously untreated women.”

20. Society position statements THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGIST [1] – The following are citations from those 2008 statements: “…it seems clear from statistical analysis of previous large studies that young women in early menopause not only having no excess cardiovascular risk, but that benefit may be shown in the future…given the powerful effects of estrogen therapy in relieving menopausal symptoms, we believe that physicians may safely counsel women to use estrogen therapy for relief of menopausal symptoms.” The AMERICAN SOCIETY OF REPRODUCTIVE MEDICINE (ASRM) [5] – “Hormone therapy is the most effective treatment for moderate-to-severe vasomotor symptoms…HRT is not indicated for primary or secondary prevention of coronary artery disease events. At the same time, perimenopausal women treated with hormones have no increased risk for CHD.”

21. Joann Manson – JAMA September 2017(lead investigator for WHI) • Among postmenopausal women, hormone therapy with Premarin (CEE) plus Provera(MPA) for median of 5.6 years or with Premarin alone for a median of 7.2 years was not associated with risk of all-cause, cardiovascular, or cancer mortality during a cumulative follow-up of 18 years.

22. Why does Post Menopause and Andropause Matter? • Life Expectancies skyrocketed ~in 1900 US women 48, now ~78! • Later retirements- Longer time to keep pace & compete with younger co-workers in the Workplace • Increase divorce rate–decrease in long monogamous relationships–senior sex matters more now with new changing partners. • Increased media exposure • More successful treatments available for sexual dysfunction • Florida is one of the Aging “Quality of Life” Capitols in the US

23. Sex • y/’seksē/ adjective Sexually attractive or exciting, feeling sexual interest, aroused. HEALTHY • VIBRANT • SEXY

24. Something This Small Can Make A BIG DIFFERENCE!

25. History of Pellets • Developed in 1939 for women who had radical hysterectomies Salmon, U., et al. Use of estradiol subcutaneous pellets in humans. Science 1939, 90: 162. • Discussed the use of estradiol and testosterone pellets for the symptoms of menopause Greenblatt, R. (1949). American Journal of OB/GYN 57, 244-301. • Widely used in Europe and Australia

26. Bio-identical Hormone Pellets • Natural, plant derived compounds- Estradiol/ Natural Testosterone • Same molecular structure as human hormones • Lasts longer than other treatments, 4-6 months • Most widely studied form of natural hormone replacement therapy • Provides steady stream of hormone in your blood • Individualized dosing • Injected under the skin • DON’T EVEN KNOW IT’S THERE!

27. Consistency • Branded meds – 10% dose to dose variability • Generic meds – 30% dose to dose variability • Biote Pellets – only 3% dose to dose variability • Not all Pellets or Pellet Providers are the same • ACOG and NAMS Recommendations: “The least amount of hormone for the shortest period of time”

28. Lowest Dosing with Best Results • Creams / Orals / Patches• absorption is very poor• need a high dose for results• ie: average dose of oral Estradiol is 1 mg daily = 120 mg / 4 mos • Pellets• absorption is very efficient• uses very low doses• ie: average dose of pellet Estradiol = 12.5 mg / 4 mos (only 0.1 mg/d)

29. Estradiol Levels- Pills, Patches vs. Pellets Smith R/ Studd, J WW Brit Jour Hosp Med, 1993, Vol 49, No 11

30. What is a “Normal” or “Optimized” Total Testosterone in Women? • <14-80 – expected range (labs say nml is ~10-50) • 70 or above – normal • 60-70 probably asymptomatic • 50-60 some loss of energy • 40-50 greater loss of energy, some loss of mental clarity, mildly decrease in: libido, muscle loss, weight gain, night sweats, sadness or anxiety • 30 – 40 all of the above but worse • 30 everything is at its worst–most common finding • 80-250 - Optimized

31. Arthritis: Hormones Could Ease Pain • 10% of men and 18% of women >60 Y.O. have osteoarthritis • BY 2020 OSTEOARTHRITIS WILL BE 4TH LEADING CAUSE OF DISABILITY • BOTH estrogen and testosterone can stimulate pre-cartilage cells, possibly reversing development of arthritic tissue • Joint pain & fatigue resolves often with pellet therapy Arthritis and Rheumatism, April 2010

32. Medical Studies • Testosterone the bone builder • Demonstrated the four fold increase in bone density over oral estrogen and 2.5 times greater than patches • 8.3% per year for pellet therapy • 3.5% per year for patches • 1-2% per year for oral estrogen OSTEOPOROSIS .Studd (1990) AM, Journal OB/GYN

33. Positive Effects of Natural Testosterone for Men & Women • Increased Energy, Vitality & Zest for Life • Improved Feeling of Overall Well-Being • Depression Relief • Anxiety Relief • Improved Cognitive Clarity • Improved Memory • Improved Focus • Prostate Protection • Breast Protection • Cardiovascular Protection • Increased Bone Strength • Increased Muscle Strength • Reduced Body Fat • Lower Cholesterol • Enhanced Libido • Enhanced Performance

34. How are Pellets Made and Absorbed • Pure estradiol and testosterone • Compressed into pellets using thousands of pounds of pressure • E-beam for sterilization – NOT autoclave • Absorbed based on cardiac output, not time released • NOT depot • 503b facility

35. What is a 503B Facility? • Pharmacy that fills gap B/N traditional compounding pharmacy and industrial manufacturing. • Allowed to make large batches of Meds. • Held to higher regulatory standards. • Must maintain full compliance with current good manufacturing practices.

36. Advantages of Pellet Therapy • Steady state of hormones, no “roller coaster” effect • 2 to 4 insertions per year – improved patient compliance • Improves lipids, insulin sensitivity and body composition • No significant weight gain • Best method to increase bone density • No increase in inflammatory markers • No increase in SHBG • No increased risk breast or prostate CA • No increase in blood clots, heart attacks or stroke

37. Bioidentical Progesterone • Progesterone is necessary in women who still have a uterus if the women is on estrogen • Can be put into creams but better absorption p.o. • Rx called Prometrium or micronized progesterone • Usually given at bedtime • Calming • Helps some women with sleep

38. Progesterone Formulation • Formulations of bioidentical progesterone: Oral, SL trit, SL RDT, Rx cream, OTC cream • Dose: QHS, BID, QID, (PMS only) • Compound vs. Generic Potency (30% tolerance) • NOTE: transdermal cream –>poor levels; poor compliance, dangerous if not maintaining midluteal serum levels; does NOT protect the uterus adequately • Capsule 200/225 mg QHS x 30 days • RDT 100 mg QD x 30 days • SL 100 mg QD x 300 days • Cream 200 mg/gm – 1 gm QID =$$$

39. Progesterone Side-Effects • Somnolence, lightheadedness, dizziness, cramping, breast or nipple tenderness • Usually only seen with oral capsules • Switch to sublingual

40. Management Concerns • Hx of Acne, prior excessive Hair Loss or Hirsutism • Hx of Menstrual Migraines • Hx of Bloating and Water Weight Gain with Menstrual Cycles • Hx of Cardiac Disease • Use of Blood Thinners • Hx of Vaginal Bleeding (Polyps, Hyperplasia, Carcinoma?) • Hx of DVT/PE or Hypercoagulable Disorder • Hx of Breast Cancer

41. Potential Insertion Issues • Uterine Spotting or Bleeding • Pellet Extrusion • Facial Breakout/ Hair Growth • Initial Breast Tenderness- if off hormones prior to beginning therapy • Fluid Retention • Occasionally occurs with the first insertion, and especially when done in hot, humid weather conditions • Swelling of the Hands & Feet • Common in hot, humid weather conditions • Less that 2% of patients experience any side effect

42. Hormone Level Testing – Accuracy : • Whether correct hormones tested(ie: Total T vs Free T vs Bioavail T or Estradiol, Estrone, Estriol vs Total Estrogens) • Time of month blood is drawn (Menstruating Women) • Interpretation of results. Optimal youthful levels canbe a standard, as well as just “normal” or “within normal limits” • Lab attention to testing sensitivity- evaluate levels with a discerning eye and repeat levels that don’t make sense

43. Potential Concerns • Abnormal uterine bleeding (underlying uterine cancer, imbalanced estrogen) • Breast discomfort/enlargement (adjustment, imbalance, overdosing) • Fibroid enlargement (predisposition, imbalance) • Uterine cancer (unopposed estrogen) / Hyperplasia • Blood clots (oral estrogens, genetic or wt predisposition) • ? Heart disease / stroke (only oral foreign and alien estrogens/progestins in WHI) • ? Breast cancer (oral progestins?) our own estrogen helps a breast cancer grow

44. Pellets often Unmask Undiagnosed Uterine Problems • If you have a uterine problem, the pellets will expose it. – i.e., Uterine fibroids, endometrial polyps, adenomyosis

45. Postmenopausal Bleeding If bleeding in first 6-8 weeks needs evaluation! • Check compliance on progesterone • Needs pelvic exam to confirm uterine source • Pelvic ultrasound (transvaginal) • Needs EMB vs GYN referral if abnormal pelvic u/s and no missed doses –pre-existing polyps, uterine fibroids, endometrial hyperplasia or malignancy?

46. Management Advisements • Caution not to overshoot on dosing – pellets cannot be removed once inserted • Evaluate any Vaginal Bleeding – US/EMB or US/Hysteroscopy D&C once workup is nml, balance w Natural Progesterone • Adjust dose & treat Acne – Spironolactone 50mg/d • Be sensitive to hair changes • Watch over patients who seek hormone dosing from an office that is not expert at hormone management

47. Pellet Benefits • Increased Energy levels • Restored interest in life • Increased Sexual Drive • Consistency in moods • Relief from anxiety and depression • Increased mental clarity and ability to FOCUS • Decreased body fat • Greater capacity for getting the body in shape

48. What is Therapy? Helps Body Return to Normal Hormonal Balance & Physiological State BASED ON • Right Kind of Hormone (Bio-Identical) • Right Amounts (Individualized Dosing) • Right Delivery System (Pellets) • Right Expert Management

49. Pellet therapy is an excellent option for healthy women and men who want to optimize their energy, libido, sensation and quality of life.

50. Thank You Jennifer S. Hayes, DO, FACOOG Visionary Centre for Women 2695 Ulmerton Rd., Clearwater, FL 727.540-0414 cell: 727-410.0195 jhayesgyn@gmail.com www.VisionaryCentreForWomen.com