UCSF Essentials of Primary Care Conference Squaw Creek, CA August 8, 2019 Disclosures relevant to this talk

Contraceptive Update: New Methods, • Bayer: litigation consultant New Guidelines • Sebela Pharmaceuticals: – Investigator trainer and proctor in phase III trial of a copper IUD (VeraCept) Michael S. Policar, MD, MPH Professor Emeritus of Ob, Gyn, and Repro Sci UCSF School of Medicine [email protected]

Do You Use the US Medical Eligibility Criteria (MEC) in Your Practice? 50% A. Every day (or more often) B. Occasionally (a few times a week)

C. Rarely (a few times a month) 17% 17% D. Never…they don’t apply to my 10% 6% practice

! E. I’ve never heard of them! ) h) n . t . m te .. n . e f a o o h MMWR. July 29, 2016 65 (3):1-103 o t t e s m ly f r e a p o o im s p rd m t e a a r m t e o w i ’ h ( fe t n r y w o e On-line at: a a d d ( fe y v ly a e e ry l ( h n e a y t e v n l … ’v E io re r I https://www.cdc.gov/mmwr/volumes/65/rr/pdfs/rr6503.pdf s a e a R v cc e O N US Medical Eligibility Criteria

Cat Definition Recommendation 1 No restriction in use Use the method

2 Advantages generally More than usual follow-up outweigh theoretical or needed proven risks 3 Theoretical or proven risks Clinical judgment that the outweigh advantages patient can use safely 4 Unacceptable health risk if the Do not use the method method is used • U.S. Selected Practice Recommendations for Contraceptive Use, 2016. MMWR July 29, 2016. 65(4);1–66

2016 Updates to the US MEC and SPR

• New recommendations for women with – Cystic fibrosis – Multiple sclerosis • Interactions with SSRIs and St. John’s wort • Addition of ulipristal acetate to ECP section • Major revisions for hormonal methods – Women with migraine headaches – Women using antiretroviral therapy – Breastfeeding & progestin-only contraception My opinion: use by clinicians should be a quality metric!! APRIL 25, 2014 Filling The “Gaps”

• Pregnancy testing and counseling • Achieving pregnancy • Basic infertility • Preconception health • Preventive health screening of women and men • Contraceptive counseling, incl reproductive life plan

CDC “Suite” of Lilly Family Planning Recommendations • 33 year old G3P3 established patient seen for family planning health screening visit • Using metformin for type 2 diabetes • Mutually monogamous relationship • Non-smoker • Recent fasting lipid profile normal • LMP 3 weeks ago; using condoms for contraception • Cervical cytology test 2 years ago was negative • Screened negative for HIV in each of her 3 pregnancies Lilly Diabetes and Contraception

• Would like to start oral contraceptives…today if possible • Progestins may increase insulin resistance, but not to the – 13 cycles of monophasic dispensed point of clinically significant ▲ blood glucose • What needs to be done in regard to… • Estrogen increases risk of thrombosis in vessels damaged – Counseling ? by diabetic vascular disease – Physical assessment? • CHC may be used in diabetics in the absence of clinically- – Screening tests? manifest vascular disease, including – Evaluating the safety of her method choice (e.g., OC –Retinopathy, nephropathy use in type 2 diabetic –Peripheral vascular disease, heart disease

SPR Appendix B: When To Start Using US MEC 2016: Diabetes Specific Contraceptive Methods

OC/P/R POP DMPA Impl LNG- Cu- IUD IUD Method When to start Back-Up Exam Hx gestational diabetes 1 1 111 1 Cu-IUC Anytime none pelvic exam

Nonvascular disease LNG-IUS Anytime If >7d* Pelvic exam i. Noninsulin-dependent 2 2 222 1 Implant Anytime If >5d* none ii. Insulin-dependent 2 2 222 1 Injection Anytime If >7d* none Nephropathy/retinopathy/ 3/4 2 3 2 2 1 CHC Anytime If >5d* BP neuropathy Other vascular disease or 3/4 2 3 2 2 1 POP Anytime If >5d* none diabetes of >20 yrs’ duration * After the first day of menstrual bleeding Exams and Tests Needed Before Diabetes and Contraception: Management Contraceptive Method Initiation 2016 • Combined hormonal contraceptives Examination Needed for – Evaluate CV risk profile (age >35, smoking, HTN, DM, lipids) Blood pressure OC, patch, ring – Use low E (↓ thrombosis) + low P (glucose control) product Weight (BMI) (weight [kg]/ height [m]2 Hormonal methods – Adjust insulin or oral hypoglycemic as necessary Bimanual examination, cervical inspection IUC, cap, diaphragm Clinical breast examination None • Progestin only methods Glucose,Lipids None – May cause insulin resistance and ▲blood glucose, but Liver enzymes None usually clinically insignificant Cervical cytology (Papanicolaou smear) None – Do not increase risk of arterial or venous thrombosis STD screening with laboratory tests None • IUDs are safe and effective choice HIV screening with laboratory tests None

Lilly: Management ADA 2015 Guidelines: Preconception Care Maintain A1c levels as close to 7.0% as possible before conception • QFP: counseling based upon shared decision making All women of childbearing Provide preconception counseling starting • MEC: can use OCs with same day start potential at puberty • SPR: assess BP, BMI only Evaluate and treat women • Retinopathy • STD: no STI screening tests indicated contemplating pregnancy • Nephropathy • Neuropathy • HIV: screening not necessary • CVD • Cervical cancer screening: up to date Evaluate and consider Contraindicated/not recommended • Physical exam: clinical breast exam optional risk/benefit profile of • Statins medications used for DM • ACEIs (AT-converting enzyme inhibitor) • Pre-pregnancy care • ARBs (AT receptor blocker) – Discuss pre-pregnancy glucose control with diabetics • Non-insulin therapy, except metformin

ADA, Diabetes Care 2015; 38 (supp 1): 77-79 Hillary Body Weight and Contraception • 19 year old G woman is seen for well woman visit 0 • Four issues about body weight relate to each method • Same male partner for the past year – Will the method cause excess weight gain? • Feeling well; no complaint of vaginal discharge, abnormal bleeding, dyspareunia – Is the failure rate higher in obese women? • Weight: 210 pounds; BMI: 32 kg/m2 – Are there medical risks attributable to the method in obese women (compared average weight)? • Using contraceptive patch; asks about LNG-IUD – What is the US-MEC category and why? • Question… • Pregnancy and childbirth among obese women are more – Are all methods acceptable relative to BMI and age? dangerous than either contraception or sterilization

Body Weight and Contraception US MEC: Age and Parity 2016 OC Patch Ring DMPA Implant IUC Tubal

Weight gain No No No Yes* No No No OC/ P/R POP DMPA Implant LNG-IUD Cu-IUC ↑ failure rate No Δ Yes # No Δ No Δ No Δ No Δ No Δ <40 yo <40 yo <18 yo <18 yo <20 yo <20 yo in obese 1 1 2 1 2 2 Medical risk in ↑DVT No No None None Difficult Surgical >40 yo: >40 yo: 18-45 yo 18-45 yo >20 yo >20 yo insertion complications obese women risk studies studies 2 1 1 1 1 1 US-MEC 2 2 2 1** 1 1 Not rated >45 yo >45 yo 2 1 * Mainly in obese adolescents and those who experience a >5% body weight increase within 6 months of DMPA initiation Nullip 11 1 1 22 # If weight > 90 kg, increase of 2-4 failures/ 100 couples/year Parous 11 1 1 11 ** < 18 yrs of age and ≥30 kg/m2 BMI SPR: Initiation of LNG-IUDs Examinations and Tests Needed Before Initiation of a Cu-IUD or an LNG-IUD Timing • The LNG-IUD can be inserted at any time if it is reasonably • Bimanual exam and cervical inspection are necessary certain that the woman is not pregnant • Screen for CT and GC according to national guidelines Need for Back-Up Contraception – Routine screening is not indicated • If inserted <7 days since LMP, no additional protection – If screening indicated, perform at the time of insertion • If inserted >7 days since LMP, abstain from intercourse or • If purulent cervicitis or GC or CT, do not place IUD ( MEC-4) use additional protection for the next 7 days

Obese Adolescent and Contraception: SPR: IUD Recommendations Management

• Prophylactic antibiotics not recommended • DMPA is not an ideal choice for her because of the potential • Pre-treatment with misoprostol not recommended for additional weight gain • Routine follow-up after IUD insertion – If DMPA chosen, baseline weight and recheck in 6 months – No routine follow-up visit is required • All methods work as well in obese women as with average – Advise a woman to return at any time weight women, except the contraceptive patch •To discuss side effects or other problems • The efficacy of emergency contraceptive pills is poor in obese women •If she wants to change the method • IUCs and implants are an excellent choice for adolescents, •When it is time to remove or replace the IUC obese women, and obese adolescents Priscilla Migraine Headache: Complications • Migraine with aura associated with stroke risk • Is a married 22 year old G2 P0 TAB2 established client who is – An increased relative risk seen for pregnancy determination visit – A low absolute risk • Her first two pregnancies were at 17 and 19 years old and Condition Odds ratio Stroke/10,000/yr occurred while using condoms No migraine or OCs 1.0 6 • She stated that she has occasional “sick headaches” Migraine without aura 1.8 – No aura before headaches begin Migraine with aura 2-4 18 – Most headaches occur during menstrual period Migraine + COCs 6-14 54 • She does not want to become pregnant now Migraine with smoking 7-10 • Interested in starting OCs Migraine+smoking + OC 34.4

Edlow AG, Bartz D. Rev in Obstet Gynecol, 2010; 3(2): 55-65

US MEC 2010: Headaches US MEC 2016: Headaches

OC/P/R POP DMPA Impl LNG- Cu- OC/P/R POP DMPA Impl LNG- Cu- IUD IUD IUD IUD Non- 1 1 1111 Non- 1 1 1111 migrainous migrainous Migraine ICIC I C Migraine Without aura Without aura 2* 1 1 111 – Age <35 2312 2 2 1 – Age >35 3412 2 2 1 With aura 4 1 1111 With aura 4423 2 3 1 – Any age * Classification is for women without any other risk I: Initiate C: Continue factors for stroke (e.g., age, hypertension, and smoking) Headaches and Contraception Management Jena • 19 years old • Differentiate migraine from non-migraine headaches • Born at 26 weeks; birth weight 1100 grams – If unclear, seek neurologist consultation • Both visual and hearing difficulties since childhood • Menstrual headaches: extended regimen OCs or NuvaRing • Now has mood problems • CHC in women with migraines without aura • Complains of irregular, heavy menses + dysmenorrhea – Use low estrogen dose product …would like her periods to stop! – Recommend frequent follow-up visits initially • Sexually active with 19 year old male – If HA worsening frequency or severity, or new • PE: BMI =34 kg/m2, BP = 118/72; mild facial hirsutism neurological symptoms, discontinue CHC • Challenge: contraception + optimize bleeding suppression • Progestin-only methods, IUC are safe and effective

PCP/ Women’s Health Visit PCP/ Women’s Health Visit

Ask re: menstrual pattern/hygiene, sexual activity Ask re: menstrual pattern/hygiene, sexual activity

+ Menstrual problems No menstrual problems + Menstrual problems No menstrual problems Sexually active*? Sexually active*?

Yes No Yes No • LNg-IUS • NSAIDs • Copper IUD • Education • DMPA • LNg-IUS • LNg-IUS • Extended OCs • DMPA • Implant • POP • Extended OCs • DMPA Extremely rarely • Extended OCs • EM ablation • POP • Hysterectomy • Patch Menstrual Manipulation for Adolescents with Menstrual Manipulation for Adolescents with Physical and Developmental Disabilities Physical and Developmental Disabilities

• Optimal suppression…reduction in amount and days of flow • POPs can be used, but efficacy is dependent on • NSAIDs decrease ovulatory menstrual bleeding by 30–40% adherence to use at the same time each day – Naproxen sodium 220-440 mg BID • DMPA results in high rates of amenorrhea by 4th dose – Ibuprofen 400-600 mg TID • LNg IUD should be considered • Combined OCs for an extended period or continuous use – Irregular bleeding is common initially, but amenorrhea over time and blood loss is decreased

ACOG Committee Opinion No. 668. Obstet Gynecol 2016;128:e20–5 ACOG Committee Opinion No. 668. Obstet Gynecol 2016;128:e20–5

Contraception + Less Bleeding Jena

Efficacy Advantages Challenges • She chose a LNg-IUD because of her desire LNg-IUS Tier 1 3–7 years - Placement (may need ↓dysmenorrhea sedation or anesthesia) for optimal bleeding control, highest - Initial BTB efficacy, and long duration of action DMPA Tier 2 Every 12 weeks - Weight gain in obese ↓dysmenorrhea adolescents • Strongly considered use of continuous OCs to reduce Extended Tier 2 Daily tablet - If immobile: VTE risk rate of hair growth and treatment of acne OCs ↓dysmenorrhea - Daily reminders • Rejected DMPA: didn’t want further weight gain - Rx interaction with EI-AED • Rejected POP: need for use at same time daily POP Tier 2 No E2 side effects - BTB - Daily reminders - Rx interaction with EI-AED Annovera Contraceptive Vaginal Ring (CVR)

Newly FDA-Approved Methods of Contraception

Photo credit: Population Council / Hallie Easley

The Basics: Annovera CVR Comparison of CVRs

• Single ring prevents ovulation for one year (13 cycles) NuvaRing Annovera – Segesterone acetate (Nestorone®) + ethinyl estradiol Lifespan 1 cycle 13 cycles – Used in 28-day cycle; monthly withdrawal (menses) Progestin release Etonogestrel Segesterone – Side effect and bleeding profile similar to NuvaRing rate 120 mcg/day 150 mcg/day – Same diameter as NuvaRing, but twice as thick EE release rate 15 mcg/day 13 mcg/day • Developed by the Population Council Diameter 54 mm 56 mm – Owned by TherapeuticsMD Thickness 4 mm 8.4 mm • FDA approval on August 10, 2018 EE: Ethinyl estradiol The Basics: Annovera CVR Annovera CVR

Use of the Annovera CVR • Efficacy – Phase III trial: 2,308 women at 27 study sites in US, Latin • In place for 21 days, then removed for 7 days to induce America, Europe, and Australia scheduled withdrawal bleeding (menses) • Women with BMI >29 kg/m2 were excluded • Can be removed for intercourse and cleaning, but not for longer than 2 hours – Of 2,111 females ≤35 years of age, perfect use Pearl Index was 2.98 per 100 woman-years of use • Does not require refrigeration • Acceptability • Water-based vaginal creams and lubricants may be used – Phase 3 study of 905 women: 89% satisfaction rate • Oil + silicone-based lubricants will alter exposure to EE – Related to ease of use, side effects, expulsions/feeling the and segesterone acetate and should not be used product and effects during sexual activity

Annovera CVR Annovera CVR

• Marketed as the “First woman-controlled, procedure- free, long-acting, reversible birth control product • Commercially available as early as 3rd quarter 2019, putting the woman in control of both her fertility and commercial release 4th quarter of 2019 menstruation” • TherapeuticsMD has agreed to provide significantly • But is it really a “LARC”? reduced pricing to Title X family planning clinics – Yes: the description is accurate • Not in same FDA contraceptive category as NuvaRing, – No: owing to need to remove it monthly and replace so must be covered under no cost-sharing rules of ACA promptly after intercourse or cleaning, is not a “forgettable” contraceptive, like an IUD or implant