Abnormal uterine bleeding when using hormonal contraceptives For the purposes of this talk we will be focusing on women of reproductive age (15-44) Rosalyn Maben-Feaster, MD,MPH Clinical Assistant Professor Department of Obstetrics and Gynecology

Disclosures None

Objectives Review expected menstrual changes with different hormonal contraceptives Review evaluation that should be performed for chronic abnormal uterine bleeding on hormonal contraceptives Review strategies to address menstrual changes due to hormonal contraceptives

Outline Introduction Terminology Potential menstrual changes Evaluation Management Conclusion

Introduction Daniels K, Daugherty J, Jones J, Mosher W. Current contraceptive use and variation by selected characteristics among women aged 15-44: United States, 2011-2013. National Health Statistics Reports; no 86. Hyattsville, MD: National Center for Health Statistics. 2015

Abnormal uterine bleeding on hormonal contraception Terminology

Cycle to Cycle variation Normal Menses Metric 5th-95th Percentiles Volume 5 – 80 cc Duration of flow 4.5 – 8 days Cycle to Cycle variation ± 2 – 20 days Frequency of cycles 24 – 38 days Fraser IS. Contraception in Women with Abnormal Uterine Bleeding. In: Shoupe D, ed. Contraception. Wiley-Blackwell, Oxford, UK; 2011. Management of abnormal uterine bleeding associated with ovulatory dysfunction. Practice Bulletin No. 136. American College of Obstetricians and Gynecologists. Obstet Gynecol 2013;122:176–85.

Abnormal Uterine Bleeding (AUB) Can be chronic or acute Types of abnormal bleeding Heavy menstrual bleeding Prolonged bleeding Excessively frequent menstruation Irregular bleeding Intermenstrual bleeding Fraser IS. Contraception in Women with Abnormal Uterine Bleeding. In: Shoupe D, ed. Contraception. Wiley-Blackwell, Oxford, UK; 2011. Munro MG, Critchley HO, Broder MS, Fraser IS. FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. International Journal of Gynecology and Obstetrics. 2011; 113:3-13.

Potential Menstrual Changes Abnormal uterine bleeding on hormonal contraception Potential Menstrual Changes

What to expect on… Combined hormonal contraception Unscheduled bleeding occurs in up to 30% in the first 3 months Decreases to 10% by third month of use May be higher in pills with lowest ethinyl estradiol (EE) dosing May be higher with extended or continuous use Varies based on generation of progestin Edelman A, Kaneshiro B. Management of unscheduled bleeding in women using contraception. In: Barbieri R, Eckler K, eds. UptoDate. August 17, 2016. Lawrie TA, Helmerhorst FM, Maitra NK, Kulier R, Bloemenkamp K, Gulmezoglu AM. Types of progestogens in combined oral contraception: effectiveness and side effects. Cochrane Database of Systematic Reviews. 2011, Issue 5. Art. No.:CD004861. Schrager S. Abnormal uterine bleeding associated with hormonal contraception. American Family Physician. 2002;65(10):2073–2080.

What to expect on… Progestin-only pill Normal menstrual cycles in 40-50% Irregular cycles or spotting in 40% Amenorrhea in 10% Edelman A, Kaneshiro B. Management of unscheduled bleeding in women using contraception. In: Barbieri R, Eckler K, eds. UptoDate. August 17, 2016. Schrager S. Abnormal uterine bleeding associated with hormonal contraception. American Family Physician. 2002;65(10):2073–2080.

What to expect on… Depot medroxyprogesterone acetate Amenorrhea is most common menstrual change 12% of patients at 3 months 46% of patients at 12 months 80% of patients at 5 years Edelman A, Kaneshiro B. Management of unscheduled bleeding in women using contraception. In: Barbieri R, Eckler K, eds. UptoDate. August 17, 2016. Schrager S. Abnormal uterine bleeding associated with hormonal contraception. American Family Physician. 2002;65(10):2073–2080.

What to expect on… Etonogestrel Implant Menstrual changes range from amenorrhea to frequent unscheduled bleeding Amenorrhea in 20% Frequent or irregular bleeding in 20% 78% report unscheduled bleeding in the first 3 months First 3 months predictive of long-term pattern Edelman A, Kaneshiro B. Management of unscheduled bleeding in women using contraception. In: Barbieri R, Eckler K, eds. UptoDate. August 17, 2016. Schrager S. Abnormal uterine bleeding associated with hormonal contraception. American Family Physician. 2002;65(10):2073–2080.

What to expect on… Levonorgestrel-releasing IUD Menstrual changes include: Prolonged bleeding – 59% Unscheduled bleeding – up to 52% Amenorrhea – 6-20% Spotting – 23-31% Dean G, Goldberg A. Intrauterine contraception: Devices, candidates, and selection. In: Barbieri R, Eckler K, eds. UptoDate. November 21, 2016. Edelman A, Kaneshiro B. Management of unscheduled bleeding in women using contraception. In: Barbieri R, Eckler K, eds. UptoDate. August 17, 2016. Schrager S. Abnormal uterine bleeding associated with hormonal contraception. American Family Physician. 2002;65(10):2073–2080.

Abnormal uterine bleeding on hormonal contraception Evaluation

Case BM is 25 year-old nulligravida with no significant past medical history who presented for evaluation of breakthrough bleeding in the setting of combined oral contraceptive pill use

Evaluation History Physical examination Assessment of compliance Review of menstrual calendar Relevant past medical history Medications E.g. anti-epileptics, antibiotics, anti-depressant, anti-coagulants Tobacco use Physical examination Including pelvic exam Schrager S. Abnormal uterine bleeding associated with hormonal contraception. American Family Physician. 2002;65(10):2073–2080.

Evaluation Laboratory tests Pregnancy test Pap test Chlamydia trachomatis/Neisseria gonorrhoeae Complete blood count Thyroid-stimulating hormone Prolactin Coagulation profile Schrager S. Abnormal uterine bleeding associated with hormonal contraception. American Family Physician. 2002;65(10):2073–2080.

Evaluation Management of abnormal uterine bleeding associated with ovulatory dysfunction. Practice Bulletin No. 136. American College of Obstetricians and Gynecologists. Obstet Gynecol 2013;122:176–85. Schrager S. Abnormal uterine bleeding associated with hormonal contraception. American Family Physician. 2002;65(10):2073–2080.

Case revisited 25 year-old nulligravida with breakthrough bleeding in the setting of combined oral contraceptive pill use History remarkable for long-term use of same pill, compliance issues Physical exam normal Labs: negative pregnancy test, pap, GC/CT tests Uterine evaluation deferred given low risk of EIN, malignancy or structural abnormality

Pathophysiology of unscheduled bleeding Compliance issues/medication interactions Decreased circulating gonadal steroid levels  decreased suppression of FSH  follicles develop and produce estradiol  additional/irregular stimulation of endometrium General Transition to atrophic endometrium Development of thin-walled, dilated superficial vessels which are fragile and more likely to bleed Munro MG, Critchley HO, Broder MS, Fraser IS. FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. International Journal of Gynecology and Obstetrics. 2011; 113:3-13.

Case revisted Management Re-education, reassurance Resolution of breakthrough bleeding with use of an alarm on her phone to remind her to take her pill at the same time each day

Abnormal uterine bleeding on hormonal contraception Management

Management of AUB on… Combined oral contraceptives CEE 0.625-1.25 mg/day EE 20 mcg/day Estradiol 0.5-1 mg/day Schrager S. Abnormal uterine bleeding associated with hormonal contraception. American Family Physician. 2002;65(10):2073–2080.

Changing the pill formulation With regards to unscheduled bleeding: Triphasic pill better than monophasic for breakthrough bleeding 21 day regimen better than 24 day regimen with 3rd generation progestin better than 2nd generation In the case of extended cycle use Discontinue for 3-4 consecutive days (must be after first 21 days) Edelman A, Kaneshiro B. Management of unscheduled bleeding in women using contraception. In: Barbieri R, Eckler K, eds. UptoDate. August 17, 2016.

Classification of Progestins By generation 1st generation 2nd generation 3rd generation 4th generation Norethindrone acetate Norgestrel Desogestrel Drospirenone Ethynodiol diacetate Levonorgestrel Gestodene Lynestrenol Norgestimate Noethynodrel Crump T. Contraception. Straight Healthcare. http://www.straighthealthcare.com/oral-contraceptives.html#progesterones. Accessed November 26, 2016. Edelman A, Kaneshiro B. Management of unscheduled bleeding in women using contraception. In: Barbieri R, Eckler K, eds. UptoDate. August 17, 2016.

Management of AUB on… Progestin-only contraceptives - 1 Schrager S. Abnormal uterine bleeding associated with hormonal contraception. American Family Physician. 2002;65(10):2073–2080.

Management of AUB on… Progestin-only contraceptives - 2 Etonorgestrel Implant Remove implant, if bleeding persists. Schrager S. Abnormal uterine bleeding associated with hormonal contraception. American Family Physician. 2002;65(10):2073–2080.

Management of AUB on… Levonorgestrel-releasing IUD First 3-6 months  reassurance > 6 months NSAIDs for 5-7days Combined oral contraceptive pills for 1-3 months Limited data ?Doxycycline for 7-14 days Empiric treatment for endometritis Consider removal and switching to a different method of contraception Dean G, Goldberg A. Intrauterine contraception: Devices, candidates, and selection. In: Barbieri R, Eckler K, eds. UptoDate. November 21, 2016. Dean G, Goldberg A. Intrauterine contraception: Management of side effects and complications. In: Barbieri R, Eckler K, eds. UptoDate. August 18, 2015

Conclusion AUB is a common complaint in women on hormonal contraception Many menstrual alterations are normal on these methods thus reassurance is important However, it is still prudent to rule out other causes that could result in AUB Management of AUB on hormonal contraceptives can often be achieved with NSAIDs, addition of estrogen or switching the type of contraceptive (within class or to another class)

References Crump T. Contraception. Straight Healthcare. http://www.straighthealthcare.com/oral-contraceptives.html#progesterones. Accessed November 26, 2016. Daniels K, Daugherty J, Jones J, Mosher W. Current contraceptive use and variation by selected characteristics among women aged 15-44: United States, 2011-2013. National Health Statistics Reports; no 86. Hyattsville, MD: National Center for Health Statistics. 2015. Dean G, Goldberg A. Intrauterine contraception: Devices, candidates, and selection. In: Barbieri R, Eckler K, eds. UptoDate. November 21, 2016. Dean G, Goldberg A. Intrauterine contraception: Management of side effects and complications. In: Barbieri R, Eckler K, eds. UptoDate. August 18, 2015. Edelman A, Kaneshiro B. Management of unscheduled bleeding in women using contraception. In: Barbieri R, Eckler K, eds. UptoDate. August 17, 2016. Fraser IS. Contraception in Women with Abnormal Uterine Bleeding. In: Shoupe D, ed. Contraception. Wiley-Blackwell, Oxford, UK; 2011. Lawrie TA, Helmerhorst FM, Maitra NK, Kulier R, Bloemenkamp K, Gulmezoglu AM. Types of progestogens in combined oral contraception: effectiveness and side effects. Cochrane Database of Systematic Reviews. 2011, Issue 5. Art. No.:CD004861. Management of abnormal uterine bleeding associated with ovulatory dysfunction. Practice Bulletin No. 136. American College of Obstetricians and Gynecologists. Obstet Gynecol 2013;122:176–85. Mishell DR. Combination Oral Contraceptives. In: Shoupe D, ed. Contraception. Wiley-Blackwell, Oxford, UK; 2011. Munro MG, Critchley HO, Broder MS, Fraser IS. FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. International Journal of Gynecology and Obstetrics. 2011; 113:3-13. Schrager S. Abnormal uterine bleeding associated with hormonal contraception. American Family Physician. 2002;65(10):2073–2080.