Contraception in the medically complicated patient

Transcription

1 Contraception in the medically complicated patient Sarita Sonalkar, MD MPH Assistant Professor Department of Obstetrics and Gynecology University of Pennsylvania

2 Disclosures } Consultant for World Health Organization

3 Context } Preventing pregnancy can be what is safest } Our goal is to help women plan a pregnancy at a time is optimal for health } Certain hormonal contraceptives may affect medical comorbidities } Certain conditions can alter the effectiveness of certain contraceptives

4 Objectives Discuss hormonal contraception effects on women with certain medical conditions Raise familiarity regarding the CDC medical eligibility criteria Discuss interactions with other medications

5 CDC Medical Eligibility Criteria Category Description When clinical judgment is available 1 No restriction for use Use the method under any circumstances 2 Benefits generally outweigh the risks 3 Risks generally outweigh benefits 4 Unacceptable health risk Generally use the method Use of method not usually recommended, unless other methods are not available or acceptable Method not to be used U.S. Medical Eligibility Criteria for Contraceptive Use, 2016.

6 How safe is contraception? Risk of death per year From any accident 1 in 2,900 From an automobile accident 1 in 5,000 From riding a bike 1 in 130,000 From combined oral contraception Age in 1,667,000 Age in 33,000 From an early surgical abortion 1 in 1,000,000 From a laparoscopic tubal sterilization 1 in 66,700 From pregnancy 1 in 6,900 Hatcher, Contraceptive Technology, 20th Ed

7 What will be covered } Age } Tobacco Abuse } Hypertension } Migraine headaches } Thromboembolic events } Obesity } Medications

8 Does age matter? } Mortality rates are low for women of reproductive age } Increased risk of cardiovascular disease with hormonal contraception } Mortality rates from cardiovascular events increase with age

9 Cardiovascular disease mortality Age Myocardial Ischemic or Venous infarction hemorrhagic thromboembolism stroke Per 100,000 woman-years

10 CDC Recommendations Combined pill, patch, ring Progestinonly pill Injection Implant LNG-IUD Copper- IUD <40=1 <18=1 <18=2 <18=1 <20=2 <20=2 Age >40= = = =1 >20=1 >20=1 >45=1 >45=2 >45=1 In healthy women, any age is category 1 or 2

11 Case 1 } 37 year old G4P2022. She smokes one-half pack per day since she was 24. She has been on combination oral contraceptives in the past and she would like to restart them today. } She is otherwise healthy. } Would you recommend COC?

12 Acute MI and Age with COC use Women < 35 Nonsmokers Non-users of 0.83 OCs* Smokers 7.78 * Incidence per 10 6 women-years WHO Lancet, 1997

13 Acute MI and Age with COC use Non-users of OCs* Users of OCs* Women < 35 Nonsmokers Smokers * Incidence per 10 6 women-years WHO Lancet, 1997

14 Acute MI and Age with COC use Non-users of OCs* Users of OCs* Women 35 Nonsmokers 9.45 Smokers 88.4 * Incidence per 10 6 women-years WHO Lancet, 1997

15 Acute MI and Age with COC use Non-users of OCs* Users of OCs* Women 35 Nonsmokers Smokers * Incidence per 10 6 women-years WHO Lancet, 1997

16 Acute MI and Age with COC use Non-users of OCs* Users of OCs* Women < Smokers Women 35 Nonsmokers Nonsmokers Smokers * Incidence per 10 6 women-years WHO Lancet, 1997

17 CDC MEC: cigarette smoking CDC risk category E+P P-only and IUDs Age < Age >35, <15 cigs per day 3 1 Age >35, >15 cigs per day 4 1

18 Case 2 } 32 yo G3P3 who has a recent diagnosis of essential hypertension. With her recent weight loss and exercise regimen she has been able to get excellent blood pressure control with a low dose of a single antihypertensive agent. } Would you recommend COC?

19 Blood pressure and COC } Mild increase in BP } Small case-control studies } Minimal changes Systolic 7-8mm Hg Diastolic 6 mm HG Cardoso Int J Gynaecol Obstet, 1995 Narkiewicz Am J Hypertens, 1995

20 COC and Hypertension Non-users of OCs (odds ratio) What is the risk for MI? HTN No 1.00 Yes 5.43 History of HTN in Pregnancy No 1.00 Yes 0.99 What is the risk for ischemic stroke? HTN No 1.00 Yes 4.59 *Note: overall risk is decreased with BP check WHO Lancet, 1997

21 COC and Hypertension Non-users of OCs (odds ratio) Users of OCs (odds ratio) What is the risk for MI? HTN No Yes HTN in Pregnancy No Yes What is the risk for ischemic stroke? HTN No *Note: overall Yes risk is decreased 4.59 with BP check 10.7 WHO Lancet, 1997

22 CDC MEC: Hypertension CDC risk category E + P P-only pill P-implant P- injection Cu- IUD P-IUD During prior pregnancy only now resolved Well controlled Systolic or diastolic Systolic >160 or diastolic > With vascular disease

23 Case 3 } 23 year old medical student that has been on a low dose combined oral contraceptive pill. She states that she has had headaches before, but over the past few months she has noted an increase in frequency. } She is currently being worked up for her headaches but she does not report any aura type symptoms. } Would you recommend COC?

24 Headaches } 93% of men and 99% of women have experienced at least one episode 1 } Migraines affect up to 28% of females of reproductive age Migraine Prevalence in the U.S. Lipton, et al, Neurology 2007

25 Migraine without Aura Recurring HA with at least 5 attacks: Lasting 4-72 hours At least 2 of the following - Unilateral location - Pulsating quality - Moderate or severe pain intensity - Aggravated by routine physical activity At least one of the following - Nausea and/or vomiting - Photophobia and phonophobia Not attributed to another disorder The International Classification of Headache Disorders, 3rd edition

26 Migraine with Aura Aura develops gradually Lasts 3-60 minutes HA begins during the aura or follows aura within 60 minutes At least 2 attacks: At least one visual, sensory, speech/language, motor, brainstem, or retinal symptom At least two of the following: At least one aura symptom is unilateral At least 1 symptom develops gradually over > 5 minutes Each symptom lasts > 5 and < 60 minutes Accompanied or followed within 60 min by a headache The International Classification of Headache Disorders, 2nd edition Cephalalgia 2004

27 Migraines } Aura = lasts 5-60 min before the headaches and are visual Flickering colorless zig zag lines Scintillating scotomata Sensory disturbances, speech disturbances, motor weakness Associated with ischemic changes à increases risk of ischemic stroke } No aura: before or during Nausea Vomiting Photophobia Phonophobia Visual blurring Generalized visual spots Flashing

28 Migraine and stroke risk } Absolute risk of stroke in young women is low (5-10 per 100,000 women years) 1 } Two- to 4-fold increase risk of stroke if history of migraine in women under 45 2,3 } OC use in women with migraines has greater risk of cerebral vascular accident 3 Especially if auras are present } Attributable risk of stroke for pill users in women with migraines 4 8 per 100,000 at age per 100,000 at age 40 1 Bousser, 2000; 2 Etminan 2005; 3 Curtis 2006; 4 LaGuardia, 2005

29 Odds ratios of ischemic stroke by history of migraine and CHC use (ages 15-49) History of migraines n=9420 Current CHC use Ischemic stroke Adjusted OR (95% CI) Migraine with aura Yes 6.08 ( ) No 2.65 ( ) Migraine without aura Yes 1.77 ( ) No 2.24 ( ) No Migraine Yes 1.39 ( _ No Reference Champaloux et al, AJOG 2016

30 CDC MEC: Migraines CDC risk category Combination methods Progesterone only pill Progesterone injectable Copper IUD implant IUD I C I C I C Non-migraine Migraine < 35; no aura Migraine > 35; no aura Migraine with aura, any age I : Initiation of method C: Continuation of method

31 Case 4 } 22 year old G0 here for contraception counseling. She has only used condoms in the past. She gives a family history of both her mom and aunt have had blood clots in their legs } Would you recommend COC?

32 Women and DVT/PE } Estrogen increases the factors associated with coagulation VII, X and fibrinogen Increase risk of VTE in combination method users Increased risk Age Personal hx of VTE Pregnancy Puerperium Obesity Surgery Air travel Certain familial coagulation disorders No increased risk Cigarette smoking Hypertension Diabetes mellitus Superficial varicose veins

33 Hormones and VTE } Risk of having an episode of VTE is highest during the 1 st year of use Does not increase with continuous use Reproductive age women and risk of VTE Absolute risk per year Not using OC 1 per 10,000 OC users (EE 30 to 35mcg) 3 per 10,000 Pregnancy 6 per 10,000

34 Women with hypercoagulable states } Women with familial thrombophilic syndromes have an increased risk of VTE when using combination oral contraception present with VTE earlier during use than lower risk users } Syndromes Factor V Leiden mutation Prothrombin G2010 A mutation Protein S, Protein C and antithrombin deficiency

35 Factor V Leiden mutation Annual risk for developing the first episode of VTE Per 10,000 Normal subjects 1 Use of COC 3 Factor V Leiden heterozygous 6 Factor V Leiden + COC s 29 } Screening not recommended

36 CDC MEC: VTE CDC risk category E+P P-only P-IUD C- IUD History of DVT/PE 3/4 2 1 Acute DVT/PE DVT/PE and established on anticoagulant therapy 3/4 2 1 Family history (first degree relatives) Major surgery With prolonged immobilization Without prolonged immobilization Minor surgery without immobilization 1 1 1

37 Case 5 } OB is a 36 year old female G4P4 with a BMI of 41. She has just undergone bariatric surgery and was referred to you from her surgeon for a contraception consultation. } Would you recommend COC?

38 Obesity } Nearly 1/3 of all Americans are obese 1 2/3 have BMI 25 } Evidence does not generally show an association of BMI with change in effectiveness of hormonal contraceptives Quality of evidence is low For all patients, there is good evidence for shortening or eliminating the pill-free interval to improve efficacy 1 Flegal, JAMA 2010

39 VTE Risk and COCs + Obesity Estimated Absolute Annual Risk of VTE per 100,000 women using COC by BMI 1,2 BMI n OR Absolute risk < BMI > 35: Risk VTE =104.5/100,000 Age 40-44: Risk VTE = 100/100,000 Age 45-49: Risk VTE = 175/100,000 Trussell, Contraception 2008

40 Bariatric Surgery } Weight loss: improved fertility } Malabsorptive procedures (Biliopancreatic diversion, jejunoileal bypass, Roux-en-Y bypass) Decrease absorption of nutrients and calories by shortening the small intestine Decreased efficacy of oral contraceptives } Restrictive procedures (laparoscopic banding, laparoscopic sleeve) Decrease storage capacity of the stomach Not associated with decreased efficacy of contraceptives

41 CDC MEC: Obesity CDC risk categories COC Patch POP Progesterone Copper and injectable IUD Ring implant IUD BMI > 30 kg/m Menarche to < 18 years and > 30 kg/ m *2 for DMPA 1 Restrictive procedures Malabsorptive procedures: *Obese adolescents who used DMPA were more likely to gain weight than obese nonusers and users of other contraception

42 Medications } Contraceptive steroids are hepatically metabolized drugs Cytochrome P450 3A4 has a role in metabolism Medications that induce this system may increase the rate of contraceptive metabolism } Efficacy can be affected in both contraception and concomitant medication Antiepileptic drugs (AEDs) Antibiotics Antiretrovirals (ARTs)

43 Antiepileptic drugs (AEDs) cytochrome 3A4 inducers cytochrome 3A4 noninducers Carbamazepine Felbamate Oxcarbazepine Phenobarbital Phenytoin Primidone Topiramate Ethosuximide Gabapentin Lamotrigine Levetiracetam Pregabalin Tiagabine Valproate Zonisamide

44 Antiepileptic drugs (AEDs) & Hormonal contraception } Certain anticonvulsants are category 3 for COC Phenytoin, carbamazipine, barbiturates, primidone, topiramate, oxcarbazapine Many common anticonvulsants are NOT contraindicated } COCs & POP may suffer first pass metabolism } Patch and ring - limited studies } DMPA No increased risk of pregnancy Reduced seizure activity 1 } LNG-IUS not compromised Mattson et al, Neurology, 1984

45 Antibiotics and COC *In general, antibiotics do not alter the efficacy of COCs } Antiinfective agents that do not decrease oral contraceptive levels Ampicillin Doxycycline Fluconazole Metronidazole Miconazole Quinolone antibiotics Tetracycline } Antiinfective agent that decreases oral contraceptive levels Rifampin ACOG Practice Bulletin No 73, June 2006

46 Antiretroviral medication } May either decrease or increase the bioavailability of steroid hormones } May alter safety and efficacy of both drugs Particularly some ritonavir-boosted protease inhibitors } Recommend condoms along with COC } Use minimum formulation of 30mcg EE } Many medications lack good data: consult CDC MEC Stringer et al., AIDS 2009

47 Etonogestrel pharmacokinetics are affected by EFV and NVP Chappell et al, AIDS 2017

48 Luteal activity in women using HAART and etonogestrel implant FIGURE 2. Assessment of progesterone levels up to 24 weeks a<er the inser?on of the etonogestrel implant in HIV-posi?ve women using or not using an?retroviral therapy. Two cutoff values (3 and 5 ng/ml) for progesterone levels were used to indicate luteal ac?vity. LPV/r-based HAART, zidovudine/lamivudine (AZT/3TC) + lopinavir/ritonavir; EFV-based HAART, AZT/ 3TC + efavirenz. Vieira, et al J Acquir Immune Defic 2014

49 Additional considerations beyond COC } Reasons to avoid hormonal contraception (progestin or estrogen) Breast cancer Hepatic adenoma or malignancies } Reasons to avoid the IUD (progestin or copper) Current uterine or cervical infections Initiation with uterine cancer, cervical cancer, pelvic tuberculosis Significant uterine distortion/uterine anomaly AIDS not controlled with HAART

50 In review } Reasons to consider progesterone only methods or copper IUD Cigarette smoking in women older than 35 years Hypertension History of VTE or high risk for VTE Coronary artery disease Cerebrovascular disease Migraine headaches in women with focal neurologic signs

51 Take home points } Hormonal contraception is much safer than pregnancy } IUDs and implants are safe in most clinical settings, and are the most effective methods } Keep aware of medication interactions when prescribing systemic hormonal contraception } Download the CDC MEC/SPR app!

52 Thank you! Questions?