New options in estrogen preparations

1. New options in estrogen preparations • Megan Fitzgerald, RN-C, MS, WHNP • Kelly Kruse-Nelles, RN-C, MS, WHNP

2. Topics to be addressed • New birth control options • Transdermal Patch • Vaginal Ring • New HRT options • Vaginal rings • Vaginal creams • Vaginal tablet • Low dose orals • Transdermal

3. Catalyst for new options of birth control • Failure rate of OC’s should be 1%, but first-year typical use failure rate is 6.2% • 60% of all unintended pregnancies occur in women who are using birth control

4. Quick Update • DMPA (Depo Provera Injection): Now has a black box warning regarding risk to BMD with prolonged (>2 years) use • Depo subQ Provera: Has same black box warning, 104 mg medroxyprogesterone acetate • LNG-IUS (Mirena IUD):Progesterone releasing IUD. Approved for up to 5 years of use. 50% of women develop amenorrhea within 12 months of insertion

5. Quick Update • Etonogestrel implant (Implanon): Provides 3 years of contraceptive protection in a single rod • Copper T 380A (ParaGard): 10 years contraceptive protection, increase in MBL, menses may increase by 1 day

6. Contraceptive Patch • 150mcg of norelgestromin/20mcg EE every 24 hours • Placed on abdomen, buttocks, upper arm, upper torso weekly for 3 weeks, fourth week is patch-free • Contraindications are identical to OC use • SE’s include: application site reactions, breast tenderness, dysmenorrhea

7. Contraceptive Patch • Do not use if over 198 pounds • Avoids first-pass metabolism • Maintains steady drug concentrations, without peak & troughs associated with OC’s.

8. Contraceptive Ring • 120mcg etonogestrel/15mcg EE • Flexible, 2.1 inches in diameter • Inserted into vagina by patient, remains for 21 days, 7days ring free • If ring is outside the vagina for more than 3 hours, backup barrier method is needed for 7 days

9. New options in managing menopause • Vasomotor symptoms • Hot flashes/night sweats • Vaginal symptoms • Vaginal mucosa can become dry, can lead to irritation, itching, discharge, infection • Vaginal atrophy • Dysparuenia • May be associated with loss of libido

10. New options in managing menopause • Urinary Tract Symptoms • Weakening/shrinking of bladder and urethral tissues • Leaking of urine • UTI’s • Frequency of urination • Bone Loss • ≈ 3% loss/year, tapers to ≈ 2% loss/year

11. Vaginal Ring • Femring: 0.5mg/24 hours or 0.1mg/24 hours, used for treatment of systemic symptoms and vaginal atrophy • Avoids first pass metabolism • Worn for 3 months • Protects against osteoporosis

12. Vaginal Ring • Estring: 7.5µg/24 hours • Avoids first pass metabolism • Worn for 3 months • Used to treat urogenital symptoms • Not intended for treatment of vasomotor symptoms

13. Vaginal Creams • Estrace: Estradiol 0.1mg/g, initial dose 2-4g/24hours for 1-2 weeks, then decrease to ½ initial dose for similar period • Premarin: CEE 0.625mg/g, 0.5-2g/24hours, given cyclically (3 weeks on, 1 week off)

14. Vaginal Creams • Ortho Vaginal: Estropipate 1.5mg/g, 2-4 g/24 hours, given cyclically (3 weeks on, 1 week off) • Creams noted on this and previous page are indicated for treatment of urogenital symptoms associated with postmenopausal atrophy of the vagina & lower genital tract

15. Vaginal Tablet • Vagifem: Estradiol 25µg/24 hours, for 2 weeks, then decrease to 1 tablet twice weekly • Relieves urogenital symptoms, no systemic relief • Has an applicator provided • Avoids first pass metabolism

16. Low-Dose Oral • Prempro: CEE 0.3mg/MPA 1.5mg or CEE 0.45mg/MPA 1.5mg • Standard Prempro dose for WHI was CEE 0.625mg/MPA 2.5mg • HOPE study showed all of these estrogen doses reduced frequency and severity of vasomotor symptoms

17. Low-Dose Oral • Daily peak/trough • First pass metabolism occurs • Increase C-reactive protein • Increases triglycerides • Increase in SHBG • Can increase cholesterol saturation of bile (risk of gallbladder disease) • Decrease of antithrombin III

18. Transdermal Patches • Estrogen only • Vivelle • Vivelle-Dot • Esclim • FemPatch • Climara • Alora • Estraderm

19. Transdermal Patches • Estrogen only • Avoids first pass metabolism • Applied twice weekly • May have application site irritation • Increases BMD

20. Transdermal Patches • Estrogen/progestin • CombiPatch • Ortho-Prefest • ClimaraPro • With all patches • May have application site irritation • Use lowest dose estrogen that will control symptoms • Increases BMD

21. Percutaneous Formulations • EstroGel: 1.25g/24 hours, metered-dose pump dispenser; applied to one arm from wrist to shoulder • Avoids peak/trough • Avoids first pass metabolism • Treats vasomotor and urogenital symptoms • Reduces LDL and triglycerides

22. Ultra-low-dose transdermal estrogen • Only indicated for women with osteopenia • Deliver 14µg of 17βestradiol/24 hours • Changed weekly • No increased risk of endometrial hyperplasia was observed (unopposed estrogen)

23. References • Fitzpatrick, L.A. (2004). Estrogen and bone health. The Female Patient, supplement February, p.4-9. • Freeman, S.B., Moore, A., Wysocki, S. (2004). Menopause Hormone Therapy: Where do we go from here? Women’s Health Care Journal, 4(3), p.8-17. • Freeman,S.B., Wysocki, S. (2005). New Option for Osteoporosis Prevention: Ultra-low-dose transdermal estradiol. The American Journal of Nurse Practitioners, 9(6), p.23-35. • Lewis, V. (2004). New hormone-therapy formulations and routes of delivery: Meeting the needs of your patients in the post-WHI world. OBG Management Supplement, July, p.11-17. • Minkin, M.J. (2004). Considerations in the choice of oral vs. transdermal hormone therapy: A review. The Journal of Reproductive Medicine, 49(4), p.311-319.

24. References • Schnare, S.M. & Shulman, L.P. (2004). The changing paradigm of reversible contraception. The Female Patient, supplement April, p.8-10. • Shulman, L.P. (2005). Nonoral contraception: Improved compliance with newer hormonal methods. The Female Patient, supplement April, p.6-10. • Thorneycroft, I.H. (2004). Unopposed estrogen and cancer. The Female Patient, supplement February, p.19-25.