Eleanor Drey, MD, EdM. Eleanor Drey, MD, EdM. University of California, San Francisco. Principles of BCM choice in chronic medical conditions

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1 Complicated Contraception Eleanor Drey, MD, EdM Associate Clinical Professor Obstetrics, Gynecology and Reproductive Sciences University of California, San Francisco Complicated Contraception Made Easy! Eleanor Drey, MD, EdM University of California, San Francisco October, 2007 Disclosure Speaker / trainer for Organon Overview Principles of BCM choice in chronic medical conditions Evidence-based references and how to use them Case examples Contraceptives as Rx for medical conditions

2 Advances in Contraception Weighing Contraceptive Risks Exciting range of reliable options Intrauterine, patch, vaginal ring, injection Extremely effective Reversible but not daily Hormonal benefits with better compliance Easy Low hormone doses Continuous low hormone levels Pregnancy Method Weighing Contraceptive Risks Pregnancy risks and risks of becoming PG Method risks Intrinsic safety of method Risks of making the disease worse Method failure Ineffective method use No backup plan if method failure Intentions for EC use or abortion Who can help? WHO Medical Eligibility Criteria Evidence based Comprehensive Up to date FREE guidelines, FREE wheel ACOG Practice Bulletin, Use of Contraception in Women With Coexisting Medical Conditions Obstet Gynecol, 2006, pp Managing Contraception Includes WHO & CDC STI guidelines

3 Who can help? WHO Medical Eligibility Criteria Considerations for use in US WHO Criteria were written to include lowest common denominator health systems Conservative given US recommendations Consider as tools not rules WHO Medical Eligibility Criteria Combined hormonal contraceptives (CHC) COC: Combined oral contraceptives P/R: Patch and Vaginal Ring CIC: Combined injectable contraceptives Progestin only contraceptives POP: Progestin only pills DMPA: Depo-MPA (DepoProvera) LNG/ETG: Implanon contraceptive implant Intrauterine contraceptives Cu-IUD: ParaGard IUD LNG-IUD: Mirena IUS WHO Medical Eligibility Criteria WHO-1: no restriction in contraceptive use WHO-2: advantages generally outweigh theoretical or proven risks If chosen, more than usual follow-up needed WHO-3: theoretical or proven risks outweigh advantages of the method Clinical judgment that this patient can safely use WHO-4: Condition represents an unacceptable health risk if the method is used

4 Who can help? WHO Medical Eligibility Criteria Evidence based Comprehensive Up to date FREE guidelines FREE wheel ACOG Practice Bulletin, Use of Contraception in Women With Coexisting Medical Conditions Obstet Gynecol, 2006, pp WHO Medical Eligibility Criteria Consider the Patch and Ring to be systemic combined hormonal contraceptives; not equivalent to OCs Risk categorization same as with OCs Assigned categories should be considered a preliminary best judgment which will be reevaluated as new data becomes available If Main Concern is Hormones? Consider Cu-IUD (ParaGard) Vaginal ring has lowest estrogen dose Unclear clinical relevance LNG-IUD (Mirena) is lowest progestin-only dose Etonorgestrel implant (Implanon) low-dose, progestin-only Copper T Contraindications New Label Previous label Pregnancy or suspicion of pregnancy Distorted uterine cavity Acute PID or history of PID Post-partum endometritis or infected abortion in past 3 months Uterine or cervical cancer or unresolved abnormal Pap smear Genital bleeding of unknown source Untreated acute cervicitis or vaginitis Wilson s disease Allergy to copper Patient or partner with multiple partners Increased susceptibility to infection (AIDS, leukemia, etc) Genital actinomycosis Current IUD in place New FDA-approved label Pregnancy or suspicion of pregnancy Distorted uterine cavity Acute PID or current behavior suggesting a high risk for PID Postpartum or postabortal endometritis in the past 3 months Known or suspected uterine or cervical malignancy Genital bleeding of unknown source Mucopurulent cervicitis Wilson s disease Allergy to copper Previously placed intrauterine contraceptive that has not been removed

5 What Routine Screening for Hormonal Contraceptive Users? What s needed? Measure BP before initiation of COC, P/R, POP, DMPA, and implants What s NOT needed for safe & effective use? Breast or pelvic exam Pap smear STI assessment or lab test screening Hemoglobin Other routine lab tests WHO Selected Practice Recommendations for Contraceptive Use, 2004 Case Study: Headaches Ms. H is a 22yo who requests OCs States that she has experienced occasional migraines over the past 9 months 2 episodes so severe that she went home from work Headaches and Contraception Tension HA is most common Muscle tightening and pain in neck, scalp Improved with sleep, analgesics, relaxation No interaction with hormones Migraine HA 18% of U.S. women had one or more migraines per year 1 Three times more common in women Common symptoms are nausea, vomiting, sonophobia, photophobia, visual spots/ flashing Diagnosing Migraines Do you have headaches? Has a doctor told you that you have migraines? How often do you have headaches? When was the last time you had a headache? What do you do when you have a headache? Does anything help your headaches? Describe your headaches. Stewart et al. Prevalence of migraine headaches in the US. JAMA 1992;267:64-69

6 AURA Focal neurological symptoms that occur just before or at the onset of the headache Not the same as premonitory or resolution symptoms: (hypo- or hyperactivity, depression, food cravings, yawning, fatigue, difficulty concentrating) Reversible symptoms that develop gradually over 5-20 minutes and last up to 60 minutes Most common - visual Stroke The absolute risk of stroke in young women is low at <1 per 10,000 women-years Risk factors: Smoking Age > 35, Obesity, FH of stroke <45 HTN, CVD, diabetes, hyperlipidemia Migraine with and without aura The International Headache Society Task Force on Combined Oral Contraceptives and HRT. Recommendations on the risk of ischemic stroke associated with use of combined oral contraceptives and HRT in women with migraine. Cephalalgia 2000;20: Migraines and Stroke Migraine and stroke: Migraine 1 (general): RR 2.2 RR Migraine without aura: RR RR Migraine with aura: RR RR Migraine, OCPs, and Stroke Synergistic effect Migraine and COC: OR 1.9 (95% CI ) 1 OR 8.7 (95% CI ) 2 OR 13.9 (95% CI ) 3 1. Etminan et al. BMJ, 2005; 330(7482): Tzourio et al. BMJ, 1995; 310: Gillum et al. JAMA, 2000, 284: Etminan et al. BMJ, January 8, 2005; 330(7482): Tzourio C et al. BMJ, 1995, 310:830-3.

7 WHO MEC 2004: Headaches Non-migrainous headaches WHO-1: all methods Migraines, < 35 years old, no aura or neuro symptoms WHO-2: COC, P/R, progestin only methods WHO-1: POP, Cu-IUD Migraines, > 35 years old, no aura or neuro symptoms WHO-3: COC, P/R WHO-2: All others WHO-1: POP, Cu-IUD WHO MEC 2004: Headaches Migraines, with aura or neurologic symptoms WHO-4: COC, P/R (at any age) WHO-2: POP, DMPA, LNG-IUD WHO-1: Cu-IUD Hormonal Contraception for Women with Migraines Considerations for CHCs Lower & consistent estrogen levels with ring Consider 20 or 25 mcg pills Consider eliminating the placebo week in women who have migraines triggered by withdrawal of estrogen ( menstrual migraines ) Regular follow-up in 1-3 months after initial Rx Must discontinue method if HAs worsen Any Progestin-Only Method Case Study: History of Depression 32yo G 0 using 20 mcg monophasic OC for 2 years; no problems Feeling sad over the past 3 months, so tried St John s Wort tablets with no effect Her family medicine clinician recommended that she try fluoxetine (Prozac) Is the Pill making her depression worse? Will anti-depressants reduce OC efficacy?

8 Do Hormonal Contraceptives Cause or Worsen Depression? Older studies suggested that progestins could Exacerbate pre-existing depression Cause depression in a small % of users More likely with progestin-only methods Newer (and better) studies show that none of these assertions is correct In depressed women, all methods are categorized as WHO WHO Medical Eligibility Criteria Study St John s Wort and OC Use St John s Wort widely used for depression Many studies show induction of CYP450 (3A4) Comparable to rifampin and carbamazepine when given for >10 days (Markowitz, NEJM 2003) Studies of SJW in OC users Hormone level ovulation Hall 2003 P, E no NA Pfrunder 2003 P 42% no no Follicle growth Murphy 2006 P 15% probable 38% yes Caution patients that OC effectiveness may be reduced CHC and Treatment of Depression and Bipolar Disorder Depression Possible effect: St John s Wort No effect SSRIs (fluoxetine), SNRIs (venlafaxine) Tricyclics (imipramine, amitryptaline) Bipolar Disorder Enzyme-inducing anti-epileptic drugs Carbamazepine, Oxcarbazine, Lamotrigine, Topiramate No effect Lithium, Valproate (Depakote), Aripiprazole (Abilify) Seizure Disorders Contraceptive goals Seizure control with anti-epileptic drugs (AEDs) Highly effective contraception Some AEDs associated with congenital anomalies Minimize interaction of AEDs and BCM Usually no change in the frequency or severity of seizure activity from CHC

9 Secondary Metabolism of Steroid Drugs AEDs: Non Inducers of Hepatic Enzymes DMPA Implant Blood Ring Patch E P Liver CYP-450 CYP-450: Cytochrome P- 450 E-I drug: enzyme-inducing drug First pass Small intestine Induction of liver enzymes within 2 days Maximal effect in 1 week Return to normal 4 weeks after stopping COC POP Generic name Ethosuximide Levetiracetam Tiagabine Valproic acid Vigabatrin Zonisamide Clonazepam Pregabalin Brand name Zarontin Keppra Gabitril Depakene, Depakote Sabril Zonegran Klonopin Lyrica Enzyme Inducing Anti-Epileptic Drugs (AEDs) Drug Brand name E reduction P reduction Carbamazepine Tegretol 42% 58% Felbamate Felbatol 13% 42% Lamotrigine Lamictal None 19% Oxcarbazine Trileptal 48% 32% Phenobarbital generic 64-72% None Phenytoin Dilantin 49% 42% Topiramate Topamax 15-33% None Thorneycroft I, Epilepsy and Behavior 2006;9:31 Management of Women Using EI-AEDs Ideal contraceptives IUCs (Mirena, ParaGard) DMPA: high efficacy; improves seizure control Unknown if DP-104 reduces seizure activity Oral contraceptives non-evidence based Use at least 35 mcg EE + high progestin product Shorten hormone free interval to 4 days or less Avoid low progestin contraceptives OrthoEvra patch; progestin only pills Thorneycroft I, Epliepsy and Behavior 2006;9:31

10 Drug Interactions Drug OC P/R POP DMPA Implant Cu IUC E-I Anticonvulsants Rifampin (E-I) Griseofulvin LNG IUC Antibiotics and Combined Hormonal BCM? Rifampin Other antibiotics Anti-retrovirals I C I C 2/3 2 2/3 2 Cardiovascular Risk Factors Independent risk factors for ASCVD Advanced reproductive age (35 or older) Smoking >15 cigarettes per day Chronic hypertension Diabetes Hyperlipidemia Cardiovascular risk is multifactorial Larger the number of risk factors Greater severity of each risk factor As risk factors increase in number or severity, a woman becomes a less appropriate CHC candidate Case Study: Chronic Hypertension 38yo G 4 P 4 woman with 2-yr h/o mild chronic hypertension Chronic hypertension discovered at last pregnancy Hypertension under fairly good control with diet management and a diuretic Considering surgical sterilization, but not yet sure of decision

11 Hypertension and Contraception Clinical issues OCs increase BP to a small degree in most women; significantly in about 5% of OC users Women with hypertension may have developed arterial wall damage Estrogen increases risk of thrombosis at site of atheroma Progestin-only contraceptives Don t affect BP (normotensive or HTN) Not associated with arterial thrombosis (MI, CVA) WHO MEC 2004: : Hypertension Any hypertension + clinical vascular disease (or) Controlled HTN + smoke >15 cigarettes /day WHO-4: COC, P/R WHO-3: DMPA Controlled moderate hypertension (S >160 or D > 100) WHO-4: COC, P/R WHO-3: DMPA Controlled mild hypertension (S= or D=90-99) WHO-3: COC, P/R WHO-2: DMPA HTN and Contraception: Management In all new start users of OCs, re-evaluate BP 3 months after initiation (P/R: no data or recommendation) Controlled hypertensive patients using CHC Evaluate CV risk profile Use low estrogen effect product Monitor BP after method initiation; if HTN worsens, discontinue If possible, co-manage with PCP Progestin-only methods and IUCs do not increase risk of either BP elevation or arterial thrombosis Diabetes and Contraception Progestins may increase insulin resistance, but not usu. clinically significant blood glucose Estrogen increases risk of thrombosis in vessels damaged by diabetic vascular disease CHC may be used in diabetics in the absence of clinically-manifest vascular disease, including Retinopathy, nephropathy Peripheral vascular disease, heart disease

12 WHO MEC 2004: Diabetes History of gestational diabetes: all are WHO-1 DM without vascular disease (+ insulin) WHO-1: Cu-IUD WHO-2: All others DM with vascular disease or DM > 20 years WHO-3: OC, P/R, DMPA WHO-2: POP, LNG/ETG, LNG-IUD WHO-1: Cu-IUD Diabetes and Contraception: Management Adjust insulin or oral hypoglycemic as necessary Combined hormonal contraceptives Evaluate CV risk profile Use low E (thrombosis) + low P (glucose control) If possible, co-manage with PCP Progestin-only methods May cause insulin resistance and blood glucose, but usually clinically insignificant Do not increase risk of arterial thrombosis IUCs are safe and effective choice Discuss preconception care with all diabetic women Family Planning as an Opportunity to Have Medical Tune Up Before Pregnancy Start PNV before pregnant Control diabetes, blood pressure, seizures, mental illness symptoms Decrease anemia Non-contraceptive benefits for BCM: Non chronic medical conditions A new way for patients (and providers) to view methods OR What method(s) should you consider even if you re NOT planning on having sex where you could get pregnant?

13 Menorrhagia or Iron-Deficiency Anemia? LNG-IUD Other hormonal methods Anticoagulation? LNG-IUD, COC, DMPA Sickle Cell Anemia? DMPA Decreases the incidence of sickle cell pain crises! LNG-IUD Other hormonal methods Decrease anemia Pregnancy carries greater risk Seizure Disorder? DMPA Increases seizure threshold! Dysmenorrhea or Endometriosis? LNG-IUD Continuous combined hormonal methods DMPA Other hormonal methods

14 Unfortunate emphasis on BCM risks and not PG risks Easier to focus on contraceptive risks than PG risks No labeling available for pregnancy No black box for pregnancy Conclusion WHO publishes excellent, evidence-based, conservative resource of recommendations for contraception in medically complicated women Risks must be balanced with risks of pregnancy Patients individual needs must be considered Acknowledgements Jody Steinauer, MD, MAS Michael Policar, MD, MPH Tina Raine-Bennett, MD, MPH Resources UCSF Family Planning Consultation Service (415) Medical Eligibility Criteria for Contraceptive Use full text on line Books Hatcher RA, et al. Contraceptive Technology Hatcher RA, et al. A Pocket Guide to Managing Contraception Darney P and Speroff L. A Clinical Guide for Contraception Guillebaud J. Contraception-Your Questions Answered 2004.

15 On-line Resources WHO Medical Eligibility Criteria for Contraceptive Use ARHP Managing Contraception Alan Guttmacher Institute Family PACT