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  • Nathan Riley, MD

Obgyno Wino Podcast Episode 8 - Use of Hormonal Contraception in Women w/ Coexisting Med Conditions

“The choice is yours to make

Time is yours to take

Some dive into the sea

Some toil upon the stone

To live is to fly

Low and high

So shake the dust off of your wings

And the sleep out of your eyes”

― Townes Van Zandt


2014 California 37 Cabernet Sauvignon from Save Me, San Francisco Wine Co.

PB#206 - Published February 2019

USMEC (U.S. Medical Eligibility Criteria for Contraceptive Use)

- published guidelines, last updated 2016, endorsed by ACOG

- https://www.cdc.gov/reproductivehealth/contraception/mmwr/mec/summary.html

- helps w/ decision-making with regards to safety of various forms of contraception

- four tiered risk stratification based on patient characteristics (age, recent pregnancy) and comorbidities (HTN, diabetes)

- big things to keep in mind: VTE, CVD, stroke

- IUDs are almost always a great/best choice...just keep that in mind

**On occasion, cat 4 may still be acceptable after conferring with other healthcare professionals if no other options available (REMEMBER, THESE ARE GUIDELINES - data often inconclusive)

VTE risk

- recall: estrogen increases circulating clotting factors

- estrogen-containing contraception carries increased VTE risk, though risk is still roughly ½ risk seen in pregnancy

- Box 2: if patient has any of these risk factors, estrogen-containing contraception is cat 3 or 4 (depending on the risk factor); check the grid

- in pts with a history of VTE, risk of recurrence depends on the clinical context: permanent (e.g factor V leiden) or reversible (e.g. surgery, trauma)

- in the former, COC (combined oral contraceptive) is cat 4; recommend non-hormonal method or progestin-only method

- in the latter, COC may still be acceptable (cat 3) as risk of recurrence is significantly less than in the inherited thrombophilias

Should I stop a COC before major surgery?

- clotting factors won’t normalize for 4-6 wks after discontinuation

- you must help them weigh the risk of VTE versus risk of unintended pregnancy during those 4-6 wks

- COC cat 4 if you anticipate prolonged immobilization post-operatively, so stop it post-op

- if surgery ambulatory, no need to stop it (cat 2)

Patch/ring and VTE

- little data

- patch delivers more estradiol than COCs, but lower peak serum (same restrictions as COC)

How does estrogen dose influence risk of VTE?

- studies have shown that decreasing estradiol dose from 50 mcg to <50 mcg that there is an associated decreased VTE risk

- no strong evidence to suggest additional benefit to risk profile with estradiol dose reduction to 20 or 10 mcg as trials are insufficiently powered to determine associations with rare adverse events such as VTE, MI, and stroke

Progestin-only methods and VTE risk

- better choice for patients with history of or at high risk of VTE, MI, or stroke (cat 2)

- older formulations (levonorgestrel or norethindrone) carry comparable risk to newer progestins (desogestrel, drospirenone, etonogestrel)

- DMPA is special, as it increases serum lipoprotein, and thus risks may outweigh contraceptive benefits (cat 3 if h/o ischemic heart disease or stroke)

- if a pt develops new VTE, ischemic cardiac event, or stroke while on progestin-only pills, implant, or LNG-IUD, they bump up to cat 3

Thrombophilias and contraception

- COCs are cat 4 if pt has known familial thrombophilia (factor V leiden, prothrombin G20210A mutation, protein C, protein S, or antithrombin deficiency)

- higher VTE risk and more rapidly development of VTE after initiation compared to pts without thrombophilia

- screening not indicated prior to starting COC (1 million pts to be screened to prevent ~2 COC-associated deaths)

- nor is it recommended to assess for MTHFR polymorphisms or fasting homocysteine levels (the former hasn’t been shown to confer increased risk; the latter is a weak risk factor for VTE at most)

SLE and contraception

- SLE carries 50-fold increased risk of MI and higher risk for VTE, esp in presence of persistently positive APS antibodies

- if positive Ig, COCs are cat 4, progestin-only cat 3

- in absence of Ig, cat 2 (absence of other CVD risk factors: HTN, smoking, >35 yrs, or hypercholesterolemia) for both COCs and progestin-only

- another note about our special friend DMPA: thrombocytopenia often seen in SLE; if so, use caution in starting DMPA, as irregular bleeding is often seen at time of its initiation (cat 3)

Contraception and risk postpartum

- table 1 below spells this out

- one additional point; it has been long thought that COC negatively impact breastfeeding, but the data is inconclusive

- bottom line is that progestin-only and IUDs are your friend in the immediate puerperium

What about safety as women get older?

- COCs cat 2 until age 50-55 yrs in absence of CVD risk factors

- discontinuation timing requires risk/benefit conversation with patient (risks of VTE, stroke, or MI versus likelihood of pregnancy)

- sterility rate is 17% at age 40, 55% at age 45, 92% at age 50 (FSH is unreliable in assessing fertility)

- other benefits: hormonal contraceptives are associated with reduced endometrial and ovarian cancer risks and can be helpful in managing AUB, bone mineral density, and vasomotor symptoms seen in perimenopause

- as age is an independent risk factor for CVD and VTE, COCs are cat 3 or 4 in presence of other risk factors such as HTN, smoking, obesity, diabetes, or migraine w/ aura

- progestin-only methods (implant, pills, or LNG-IUD) are reasonable alternatives (and the LNG-IUD is also helpful in AUB-O!)

- DMPA special again: used chronically, it leads to decreased BMD, so cat 2 in women >45


Obesity

- COCs cat 2

- body weight doesn’t seem to influence efficacy of contraception significantly, though more studies need to be done (esp in BMI >40)

- as steroid hormones tend to redistribute, pharmacokinetics likely affected at higher BMIs (ex: continuous COC use or using 30-35 mcg estradiol pill may work better than 20 mcg pill)

- there was a large, prospective cohort (52,000 people!!) found higher failure rate in BMI >35 even after adjusting for age, parity, and education, but this difference disappeared when comparing 24/4 regimen compared with 21/7 regimen

- patch/ring even less data but have been found to be more effective than barrier methods alone in obese women

- as obesity is an independent risk factor for VTE, slightly higher risk but still far lower risk than that seen in pregnancy/puerperium

- having said that, progestin-only methods might be a better choice >35 yrs

- DMPA does doesn’t matter (150 versus 104 SQ)

- weight gain is still something many patients will report w/ DMPA

- LNG-IUD may be particularly groovy because obese women are at increased risk for endometrial hyperplasia and AUB

What if they had bariatric surgery?

- absorptive compromise - Roux-en-Y gastric bypass or biliopancreatic diversion: oral contraception is all cat 3 (decreased absorption and thus efficacy); non-oral cat 1

- restrictive surgeries - banded gastroplasty, sleeve gastrectomy: oral contraception is fair game

A comment on St. John’s wort

- if a woman is taking St. John’s wort for depression, COCs, progestin-only pills, and implant are cat 2

- St. John’s wort is a hepatic enzyme inducer, thus steroid hormones metabolized more quickly

Migraines, migraines, migraines…

- 25% of women w/ migraines report aura

- migraines tend to be pulsating, multiple hours, unilateral

- to diagnose migraine w/ aura, you need at least two attacks characterized by symptoms (visual, sensory, speech, motor, retinal) and several characteristics about these symptoms (check Box 3 in the PB for details)

- progestin-only cat 1 regardless

- COCs cat 2 if no aura and no other stroke risk factors

- COCs cat 4 if aura

How about HTN?

- BP <140/90 mmHg all methods OK

- BP 140-159/90-99 mmHg hormonal methods are cat 3

- BP ≥160/100 mmHg hormonal methods are cat 4

- little data on risk adjustment if HTN well-controlled through medication (so use caution; reasonable to try hormonal method if pt is ≤ 35 yrs non=smoker without evidence of end-organ damage - if any other CVD risk factors, just go with a non-hormonal method

- if you do a trial, COCs require closer follow-up of BPs (if you see a jump, switch method)

- no need if using a progestin-only method

- EXCEPT: DMPA - it’s cat 3 because of its effect on lipoproteins (must weigh cardiovascular risk with risk of unintended pregnancy in setting of HTN)

Diabetes and contraception safety

- If white class D (>20 yrs) or worse (retinopathy, nephropathy, etc.), COCs are cat 3 or 4 depending on severity of disease

- DMPA is again cat 3

- otherwise, uncomplicated (even if on insulin), hormonal methods are cat 2

Breast cancer and contraception safety

- hormonal contraception cat 1 if no personal history of breast ca, even if BRCA mutation carrier or family hx

- if personal history, hormonal contraception is cat 4 (remember many breast cancers are hormonally sensitive)

- if NED ≥ 5 yrs cat 3

- paragard is your best bit if personal hx of breast ca

- LNG-IUD special: no increased risk of recurrence with LNG-IUD; if on Tamoxifen, LNG-IUD may additionally mitigate the increased risk of endometrial polyps

- HOWEVER, in patients in whom breast cancer diagnosis was made with LNG-IUD in place, continued use of the IUD was associated with increased recurrence risk

Gyn cancer and contraception safety

- once diagnosed, surgery is generally indicated

- while awaiting surgery: hormonal contraception is cat 1 or 2

- if surgery doesn’t result in sterility, same rules apply

- if dx of endometrial hyperplasia or malignancy and patient declines surgery or is a poor surgical candidate, LNG-IUD or DMPA may be used

GTD considerations

- as hCG monitoring is important, effective contraceptive needs to be enacted

- if pt was treated with D&C and hCG levels are falling or undetected or if hCG levels are elevated by intrauterine disease is not suspected, hormonal methods are cat 1 or 2

- due to concerns for possible bleeding, infection, or perforation, new IUD placement in patients with persistently elevated hCG levels or suspected intrauterine disease (cat 4)

Concomitant antiepileptics, antiretrovirals, antimicrobials, or anticoagulants

- many of these meds induce hepatic enzymes, so metabolized quick, and greater likelihood of contraceptive failure

- with hepatic inducers, DMPA and LNG-IUD remain cat 1; etonogestrel implant is cat 2, COCs or progestin-only pill are cat 3

- recommend formulations with higher doses of estradiol (30-35 mcg), longer half-life progestins (drospirenone, desogestrel, levonorgestrel), and hormone-free intervals of <7 days to avoid escape ovulation

- list of hepatic-inducing antiepileptics can be found in the PB (carbamazepine, phenobarbital, phenytoin to name a few)

- lamotrigine: may need higher dose as estrogen in COCs may cause decrease in levels

- same recommendations for rifampin (DMPA and LNG-IUD)

- LASTLY: anti-coagulation

- progestin-only is cat 2

- remember that warfarin or other chronic anti-coagulation tx may lead to HMB or ruptured ovarian cysts

- LNG-IUD or DMPA → added benefits of preventing cyst formation

- if recurrent VTE, COCs can be considered case by case while on anti-coagulation

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