1. 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

2. Disclosures
None

3. 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

4. Outline Introduction Terminology Potential menstrual changes
Evaluation
Management
Conclusion

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

6. Abnormal uterine bleeding on hormonal contraception
Terminology

7. 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 American College of Obstetricians and Gynecologists. Obstet Gynecol 2013;122:176–85.

8. 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.

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

10. 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.:CD
Schrager S. Abnormal uterine bleeding associated with hormonal contraception. American Family Physician. 2002;65(10):2073–2080.

11. 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.

12. 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.

13. 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.

14. 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.

15. Abnormal uterine bleeding on hormonal contraception
Evaluation

16. 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

17. 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.

18. 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.

19. Evaluation
Management of abnormal uterine bleeding associated with ovulatory dysfunction. Practice Bulletin No 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.

20. 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

21. 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.

22. 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

23. Abnormal uterine bleeding on hormonal contraception
Management

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

25. 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.

26. 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. 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.

27. 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.

28. 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.

29. 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

30. 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)

31. References
Crump T. Contraception. Straight Healthcare. 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, National Health Statistics Reports; no 86. Hyattsville, MD: National Center for Health Statistics
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.:CD
Management of abnormal uterine bleeding associated with ovulatory dysfunction. Practice Bulletin No 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.