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Estrogen in 2010

Estrogen in 2010. Dr Dedeshya Holowenko. Disclosures. none. Objectives. Indications for estrogen therapy Risks of estrogen therapy Transdermal vs oral estrogen. Indications for Estrogen?. Indications for Estrogen Therapy. Atrophic vaginitis very common in the post menopausal woman

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Estrogen in 2010

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  1. Estrogen in 2010 Dr Dedeshya Holowenko

  2. Disclosures • none

  3. Objectives • Indications for estrogen therapy • Risks of estrogen therapy • Transdermal vs oral estrogen

  4. Indications for Estrogen?

  5. Indications for Estrogen Therapy • Atrophic vaginitis • very common in the post menopausal woman • Causes decreased libido, urinary irritability, dysparenia and relationship discord • Natural Menopause • Peri and early post menopause (< 10 yrs) • POF, Surgical menopause, Chemotherapy and radiation therapy where ovarian function has been affected

  6. Risks of Estrogen Therapy

  7. Risk of Estrogen Therapy • Endometrial Cancer-yes • Breast cancer-no • Cardiovascular-timing • DVT/PE-consider route

  8. Endometrial Cancer

  9. Endometrial Cancer • Lifetime risk 2.7% • Risk factors for endometrial cancer • Obesity • Unopposed estrogen therapy (eg. compounded estrogen+/- progesterone cream) • Prolonged tamoxifen use • Anovulation (not associated with BCP) • Polycystic ovarian syndrome • Estrogen secreting tumors • Nulliparity • Late menopause (increased frequency of anovulatory cycles) • History of complex endometrial hyperplasia

  10. Breast Cancer

  11. Breast Cancer • Estrogen alone does NOT increase the incidence of breast cancer (WHIS). • Estrogen + Provera increases the incidence of breast cancer from a baseline incidence of 45/1000 women to 47/1000 women

  12. Risk Factors For Breast Cancer 50 8 year ERT* 5 years of CCEPT use 10 years of CCEPT use 15 years of CCEPT use Late Menopause (10 year delay) Body Mass Index (10 kg increase) Alcohol consumption (2 drinks/day) Lack of regular exercise Weight gain after menopause (20 kg or more) 40 30 Additional Cancers per 1,000 Women 20 10 * 0 Baseline No HRT use 45/1000 Women 50-60 years SOGC – 2002 * WHI JAMA 2004

  13. Breast Cancer Risk • decreased risk with premarin (estrogen only) • Increased risk with 5 yrs HRT (premarin+ medroxyprogesterone-MPA) – 2/1000 • Increased risk with exercise < 4hr per wk – 27/1000 • Increased risk with 2 serving /d alcohol - 27/1000 • Increased risk with 20 kg weight gain 45/1000

  14. Cardiovascular risk

  15. HT HT Hypothetical Pathogenic Sequence No HT Adventitia MMP-9 FibrousCap FibrousCap Media InternalElasticLamina FibrousCap Plaque Plaque Necrotic Core Necrotic Core Plaque Fatty Streak/Plaque HT Early & Continued HT Late Mural Thrombus Age 35-45 years Age 45-55 years Age 55-65 years Age >65 years

  16. Coronary Events with HT Younger Vs. Older Women Less than 60 years old • Decreased risk CHD by 30% • OR 0.68 (0.48 – 0.95) Greater than 60 years old • First year increased risk CHD • OR 1.47 (1.12 – 1.92) • 2nd year decreased risk ofCHD by 20% • OR 0.79 (0.67 – 0.93) Salpeter, JGIM 2006; 21:363-366

  17. Coronary Events with HT Younger Vs. Older Women Take Home Message: “Hormone Therapy reduces the risk (protects) of CHD events in younger postmenopausal women. In older women HT increases, then decreases risk over time” Salpeter, JGIM 2006; 21:363-366

  18. Thromboembolic Events • Consider transdermal estrogen

  19. Thromboembolic risk of HRT • Oral estrogens have a higher risk of thromboembolic events than transdermal estrogen

  20. Transdermal vs. Oral:First-pass Metabolism Oral Therapy Tablet must pass throughthe digestive system and liver before reachingcirculation Transdermal therapy Hormone has immediate access to the circulation without concerns for the liver and digestion

  21. Oral HRT and Liver Dysfunction • Oral estrogens can inducethe production of numeroushepatic proteins, such as: • angiotensinogen • sex-hormone-binding globulin • Increased clotting factors • High estrogen concentrationsin the liver increases metabolic burden • increases biologically active metabolites • Impaired hepatic function can lead to hyperestrogenism • may have substantial estrogenic side effects Mueck AO: Münchner Medizinische Wochenschrift 1997; 139:495–9.

  22. Smoking and HRT • Smoking reduces endogenous estrogen levels • Nicotine may increase hepatic metabolism of estrogen via CYP 450 enzymes • Smoking increases SHBG • Consider transdermal delivery to avoid first-pass liver metabolism (if they are already on an estrogen) Lobo, JRM 37:77,1992 Can. Cons. Men. Osteo. JSOGC:20, 1998

  23. Oral or Transdermal? Oral Transdermal Decreased libidox  High TG w/ caution  Hypertension w/ caution  Smokers w/ caution  Post thromboembolismx?  Thyroid disorders w/ caution  Disorders of the liver w/ caution  Disorders of the gall bladder w/ caution  Disorders of the pancreas w/ caution  Disorders of the stomach or intestine w/ caution  Mueck AO: Münchner Medizinische Wochenschrift 1997; 139:495–9.

  24. Questions?

  25. Bioidentical Estrogens

  26. FDA approved Bioidentical Hormones

  27. Compounded Pharmacy Advertisement

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