ACOG Practice Advisory: Counseling Patients About Breast Cancer Risk and Hormonal Contraception

SUMMARY:

ACOG has reaffirmed a practice advisory that had initially been in response to a prospective cohort study. The results from the paper by Mørch and colleagues (NEJM, 2017) was based on Danish nationwide registries (see ‘Related ObG Topics’ below) and identified the following

Overall risk of breast cancer in current or recent users compared to women who never used hormonal contraception

• Increased Risk of breast cancer: Relative Risk (RR): 1.20 (95% CI, 1.14 to 1.26)
• Risk increased with duration of use: RR 1.09 (95% CI, 0.96 to 1.23) at < 1 year vs 1.38 (95% CI, 1.26 to 1.51) after > 10 years (P=0.002)
• Risk remains elevated after ≥5 years but not < 5 years

Oral Combined Contraceptives

• Little evidence of major differences between various OCPs after statistical adjustments for multiple testing

Levonorgestrel-releasing intrauterine system (LNG-IUD)

• No significant differences compared to OCPs
• RR of breast cancer was 1.21 (95% CI, 1.11 to 1.33)

Contraceptive implants

• Few breast-cancer events among users of the progestin-only implant and depot medroxyprogesterone acetate

KEY POINTS:

Relative vs Absolute Risk

Absolute risks remain low

• Overall: 1 additional case of invasive breast cancer for every 7,690 women using hormonal contraception
• Women <35 years: 1 additional case of invasive breast cancer for every 50,000 women using hormonal contraception

Benefits of Hormonal Contraceptives

ACOG addresses these benefits clearly in this Practice Advisory

• Non-hormonal benefits (see ‘Related ObG Topics’ below)
  • Decreased risk of ovarian, endometrial, and colon cancer
  • Overall cancer risk may be lower in hormonal contraceptive users despite possibility of small increased breast cancer risk
• Hormonal benefits
  • Maternal mortality rate in the US: 26.4 deaths per 100,000 women (2015)
  • The above risk is twice that of developing invasive breast cancer in the NEJM study

Study Limitations

ACOG highlights the following

• Study confounders not assessed in this study
  • Breastfeeding | alcohol consumption |physical activity
• Study may not be generalizable
  • Only a northern European population was included
• More study required regarding relationship between progestin-only contraceptives and breast cancer risk
  • Study results were inconsistent regarding progestin-only formulations

Counseling recommendations

ACOG supports shared decision making and counseling should include the following

This recent study showed that women who use hormonal birth control methods may have a small increased risk of breast cancer, but the overall risk of breast cancer in hormonal birth control users remains very low

Hormonal birth control is very effective in preventing pregnancy and may lower a women’s overall risk of cancer by providing protection against other types of cancer

There are nonhormonal methods of birth control that are also good options

Women can do things to help lower their risk of breast cancer, like breastfeeding, getting more exercise, and limiting alcohol intake

Learn More – Primary Sources:

Practice Advisory: Hormonal Contraception and Risk of Breast Cancer

CDC Guidelines on How to Start Combined Hormonal Contraceptives

CLINICAL ACTIONS

Combined hormonal contraceptives contain both estrogen and a progestin. This contraceptive category includes combined oral contraceptives, transdermal patches and vaginal rings. They are effective when taken as directed, reversible and can be used by women of all ages.  It is important to alert women that they will not protect against STDs and other preventative measures will be required to protect against infections.  The following assumes there are no contraindications to estrogen component (e.g., breast cancer, hyperlipidemia, liver disease etc.). Only BP is “essential and mandatory” and when BP cannot be measured by a provider, a measurement obtained in other setting can be reported by the woman to her provider. The following are highlights from the CDC recommendations on initiation:  

Initiation – Criteria and Timing

Obesity

Patient with Amenorrhea (Not Postpartum)

Postpartum (Breastfeeding)

Postpartum (Not Breastfeeding)

Postabortion (Spontaneous or Induced)

Need for Follow-up

Switching from Another Contraceptive Method

Switching from an IUD

VTE WARNING Category 3 or 4

Initiation – Criteria and Timing  

CDC Criteria to determine with ‘reasonable certainty’ that woman is not pregnant (≥1 of the following)  

• ≤7 days after the start of normal menses 
• No sexual intercourse since the start of last normal menses 
• Correctly and consistently using a reliable method of contraception 
• ≤7 days after spontaneous or induced abortion 
• Within 4 weeks postpartum 
• Fully or nearly fully breastfeeding (exclusively breastfeeding or the vast majority [≥85%] of feeds are breastfeeds), amenorrheic, and <6 months postpartum  

Timing  

• Start at any time if ‘reasonably certain’ not pregnant criteria are met  

Back-Up Contraception 

• If combined hormonal contraception begun within the first 5 days since menstrual bleeding started 
  • No additional contraceptive protection is needed 
• If combined hormonal contraception started >5 days since menstrual bleeding started 
  • Abstain from sexual intercourse or  
  • Use additional contraceptive protection for the next 7 days 

Obesity

• Combined hormonal contraceptives are a category MEC 2 and therefore can be prescribe to women regardless of BMI
• Obesity is a risk factor for VTE, but lower than risk from pregnancy

Patient with Amenorrhea (Not Postpartum) 

• Timing 
  • Start at any time if ‘reasonably certain’ not pregnant criteria  
• Back-up contraception 
  • Abstain from sexual intercourse or  
  • Use additional contraceptive protection for the next 7 days 

Postpartum (Breastfeeding) 

• Timing 
  • Start when the woman is medically eligible (MEC guidance) and meets ‘reasonably certain’ not pregnant criteria  
• US MEC postpartum guidance (combined hormonal contraceptives)  
  • Avoid combined hormonal contraceptives during the first 3 weeks (risk of VTE)  
  • Avoid combined hormonal contraceptives during the first 4 weeks (concerns regarding breastfeeding performance)  
  • Caution: Women who are postpartum with additional risk factors for VTE should not use combined hormonal contraceptives 4–6 weeks after delivery (please see ‘Primary Sources’ and ‘Related ObG Topics below for further guidance on medical eligibility)
• Back-up contraception  
  • <6 months postpartum, amenorrheic, and fully or nearly fully breastfeeding (exclusively breastfeeding or the vast majority [≥85%] of feeds are breastfeeds)  
    • no back-up needed 
  • If not in the above category, and patient is ≥21 days postpartum and has not experienced return of her menstrual cycle  
    • Abstain from sexual intercourse or  
    • Use additional contraceptive protection for the next 7 days 
  • Menstrual cycles have returned and >5 days since menstrual bleeding started 
    • Abstain from sexual intercourse or  
    • Use additional contraceptive protection for the next 7 days 

Postpartum (Not Breastfeeding)

• Timing 
  • Start when the woman is medically eligible (MEC guidance) and meets ‘reasonably certain’ not pregnant criteria  
• US MEC postpartum guidance (combined hormonal contraceptives)  
  • Avoid combined hormonal contraceptives during the first 3 weeks (risk of VTE)  
  • Caution: Women who are postpartum with additional risk factors for VTE should not use combined hormonal contraceptives 4–6 weeks after delivery (Please see ‘Primary Sources’ and ‘Related ObG Topics’ for further guidance on medical eligibility)
• Back-up contraception 
  • <21 days postpartum 
    • No additional contraceptive protection needed
  • ≥21 days postpartum and whose menstrual cycles have not returned  
    • Abstain from sexual intercourse or  
    • Use additional contraceptive protection for the next 7 days 
  • Menstrual cycles have returned and it has been >5 days since menstrual bleeding started 
    • Abstain from sexual intercourse or  
    • Use additional contraceptive protection for the next 7 days 

Postabortion (Spontaneous or Induced) 

• Timing: 
  • Start combined hormonal contraception within the first 7 days following first-trimester or second-trimester abortion, including immediately postabortion  
• Back-up contraception
  • If combined hormonal contraception not started at time of surgical abortion  
    • Abstain from sexual intercourse or  
    • Use additional contraceptive protection for the next 7 days

SYNOPSIS:

There may be times there is uncertainty whether a woman is pregnant. According to the CDC, “the benefits of starting combined hormonal contraceptives likely exceed any risk; therefore, starting combined hormonal contraceptives should be considered at any time, with a follow-up pregnancy test in 2–4 weeks.” In a situation where a woman needs to use additional contraceptive protection when making the switch to combined hormonal contraception, consider continuing previous contraceptive methods for 7 days after starting combined hormonal contraception

KEY POINTS

Need for Routine Follow-Up

• The CDC states that if a patient is otherwise healthy, “No routine follow-up visit is required”
• Women should be advised to return at any time to discuss
  • Side effects | Desire to change contraceptive method | Any other issues or concerns
• At other routine visits, assess
  • Patient satisfaction | Concerns
  • Change in health status and medications that may impact use of combined hormonal contraceptives (e.g., move to MEC category 3 and 4 conditions)
  • Blood pressure
  • Weight changes, including if patients are concerned regarding perceived changes

Switching from Another Contraceptive Method 

• Timing 
  • Start at any time if ‘reasonably certain’ not pregnant criteria are met  
  • Waiting for her next menstrual cycle is unnecessary
• Back-up contraception  
  • If combined hormonal contraception started >5 days since menstrual bleeding started 
    • Abstain from sexual intercourse or  
    • Use additional contraceptive protection for the next 7 days 

Switching from an IUD

• If the woman has had sexual intercourse since the start of her current menstrual cycle and it is >5 days since menstrual bleeding started, consider any of the following  
  • Retain the IUD for at least 7 days after combined hormonal contraception initiated and return for IUD removal or  
  • Abstain from sexual intercourse or use barrier contraception for 7 days before removing the IUD and switching 
• If cannot return for IUD removal and has not abstained from sexual intercourse or used barrier contraception for 7 days 
  • Use emergency contraceptive pills at the time of IUD removal 
  • Combined hormonal contraceptives can be started immediately after use of emergency contraceptive pills (except for ulipristal acetate) 
  • Ulipristal acetate: Combined hormonal contraceptives can be started no sooner than 5 days after use  
• Note: The CDC considers IUDs separately because in theory, if a woman has had sexual intercourse and it is >5 days from the time of her period, residual sperm could still potentially be active with a risk for fertilization

VTE WARNING Category 3 or 4 (risk outweigh benefits or unacceptable risk)

The following factors elevate risk of VTE sufficiently to classify as 3 or 4 and alternate methods should be used

• Smoking ≥35 years of age
• Postpartum <21 days
• Postpartum 21-42 days with additional risk factors
  • ≥35 years of age | Previous VTE | Thrombophilia | Immobility | Transfusion at delivery | Peripartum Cardiomyopathy | BMI ≥30 | PPH | Postcesarean delivery | preeclampsia | smoking
• Major surgery with immobilization
• History of DVT or PE
• Hereditary thrombophilia including antiphospholipid syndrome
• Inflammatory Bowel Disease with
  • Active or extensive disease | Surgery | Immobilization | Steroid use | Vitamin deficiencies | Fluid depletion
• SLE with positive or unknown antiphospholipid antibodies
• Superficial DVT (acute or history)

Learn More – Primary Sources:

CDC: U.S. Selected Practice Recommendations for Contraceptive Use, 2016

CDC MEC: Classifications for Combined Hormonal Contraceptives

ACOG Practice Bulletin 206: Use of Hormonal Contraception in Women With Coexisting Medical Conditions

CDC: Effectiveness of Family Planning Methods

WHO: Family planning/contraception methods

Are Drug Interactions between Antibiotics and Hormonal Birth Control a Reality or Myth?

BACKGROUND AND PURPOSE: 

• Limited data regarding hormonal contraception and antibiotics 
• Rifamycin antibiotics (rifampin, rifabutin) induce key hepatic enzymes that are part of hormonal birth control pathway metabolism but this mechanism may not be generalizable to other more common antibiotics 
• There is data that most pharmacists recommend backup contraception for women who use antibiotics with hormonal contraception due to concern for unintended pregnancy 
• Simmons et al. (AJOG, 2018) sought to examine potential interactions between non-rifamycin antibiotics and hormonal contraceptives 

METHODS: 

• Systematic review 
  • Search included trials, cohort, case-control, and pharmacokinetic studies when non-rifamycin antibiotics and hormonal contraceptive that addressed: 
  • pregnancy rates 
  • pharmacodynamics 
  • pharmacokinetic outcomes  
• Reviews were independently assessed by two authors to avoid bias 
• Risk of bias was assessed using the USPSTF evidence grading system 
• Findings were tabulated by drug class 

RESULTS: 

• Study quality ranged from good to poor and addressed only oral contraceptive pills, emergency contraception pills, and the combined vaginal ring 
• Ethinyl estradiol was affected when administered with dirithromycin (a macrolide) and showed increased clearance but this effect was not seen with any other drug 
• Two studies demonstrated no difference in pregnancy rates in women who used oral contraceptives with and without non-rifamycin antibiotics 
• There was no observed differences in ovulation suppression or breakthrough bleeding in any study that combined hormonal contraceptives with any antibiotic 
• No significant decreases in any progestin pharmacokinetic parameter occurred during co-administration with any antibiotic 

CONCLUSION: 

• Clinical and pharmacokinetic outcome studies do not support the existence of a drug interaction between hormonal birth control and non-rifamycin antibiotics 
• Authors do note that  
  • There may be individual differences in drug metabolism and they suggest a small subset of women (likely <1%) may be at risk for hormonal contraceptive failure when taking antibiotics  
  • Switching to another contraceptive or backup method if compliance is good and there is an unintended pregnancy 
  • Obesity may play a role in drug metabolism that could impact these study results 

Learn More – Primary Sources: 

Drug interactions between non-rifamycin antibiotics and hormonal contraception: a systematic review 

IUDs and Implants: How to Manage Potential LARC Complications

Use of long-acting reversible contraceptive (LARC) methods, both intrauterine devices and subdermal contraceptive implants, has increased dramatically in the past ten years.  Although the risk of complications is low, as use increases the absolute number of complications will increase.

CLINICAL ACTIONS:

Intrauterine device:

• Pain
  • Lidocaine paracervical block reduces pain scores on insertion
  • Misoprostol does not improve pain scores and may be associated with nausea and vomiting
• Strings not visualized
  • Rule out pregnancy and expulsion
  • Recommend backup contraception until IUD position can be verified
  • Recommend emergency oral contraceptives (if appropriate)
  • Ultrasound and X-ray of abdomen and pelvis can be used for localization
• Possible expulsion
  • IUDs seen in the cervix are partially expelled and should be removed
    • Replacement or use of another method are both acceptable options
  • Low-lying IUDs (lower uterine segment) can be expectantly managed
• Risk factors for expulsion include
  • Young age
  • Heavy menstrual bleeding and dysmenorrhea
  • Placement postpartum or post second trimester abortion
  • Presence of anatomic distortion of the uterine cavity
• Uterine perforation
  • Is rare and generally asymptomatic
  • Usually occurs at the time of insertion
    • Do not use misoprostol routinely prior to insertion in nulliparous women but may be considered with difficult insertions
  • Rule out pregnancy and remove surgically unless the surgical risks of removal outweigh the benefits
• PID
  • Can be treated with the IUD left in situ
  • Consider removal if no clinical improvement after 48-72 hours of antibiotics
• Pregnancy with an IUD in place
  • Remove the IUD if the strings are visible or IUD within the cervix
  • IUD can be removed at time of procedure if patient elects termination
  • Evaluate for ectopic pregnancy

Implant:

• Infection prevention
  • Use antiseptic technique and cover the insertion/removal site
  • Skin flora are the most common cause of infection
  • Remove implant if infection does not resolve
• Bruising
  • Is common
  • Ice and anti-inflammatory medication can help
• Nonpalpable implant
  • Locate with high frequency (>/= 10 MHz) ultrasound probe, two dimensional X-ray, or CT scan/fluoroscopy
  • Obtain a serum etonogestrel level if all studies are negative/equivocal
  • Refer to a surgeon with knowledge of the anatomy of the arm if implant is within muscle or neurovascular bundle
• Pregnancy
  • Is rare
  • Remove the implant if the pregnancy is to be continued
  • Rule out ectopic pregnancy

SYNOPSIS:

LARCs are highly effective contraceptives with a low risk of complications.  Those mentioned above should be discussed with patients as part of informed consent.

KEY POINTS:

• Recognition and prompt diagnosis/treatment of the untoward outcomes described above are important aspects of care
• Overall, complication rates are low and LARCs remain a very effective mode of birth control

ICD-10 codes:

• Z30.49 check/reinsertion/removal of implant
• Z30.430 insertion of IUD
• Z30.432 removal of IUD
• Z30.433 removal and reinsertion of IUD

Learn More – Primary Sources:

ACOG Committee Opinion 672: Clinical challenges of long-acting reversible contraceptive methods