Counseling Patients About Breast Cancer Risk and Hormonal Contraception

SUMMARY:

ACOG reaffirmed a practice advisory in 2022 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

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