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

Does LNG IUD Inserted Immediately Postpartum Affect Breastfeeding Success?

BACKGROUND AND PURPOSE:

• There is limited data on whether the timing of levonorgestrel (LNG) IUD placement postpartum can affect breastfeeding
• Turok et al. (AJOG, 2017) examine the effect of immediate versus delayed postpartum LNG IUD placement on breastfeeding outcomes

METHODS:

• Noninferiority randomized controlled trial
• Women were categorized into the following groups
  • Immediate postpartum insertion within 30 minutes (132 women)
  • Delayed (12 weeks postpartum) insertion (127)
• Ultrasound guidance not required but routinely used
• Primary outcome was breastfeeding continuation at eight weeks
• Secondary outcome was time to lactogenesis
• Subjects were followed for 6 months

RESULTS:

• Breastfeeding at 8 weeks in immediate group was not inferior to delayed group
• Time to lactogenesis was noninferior to the delayed group (mean difference between groups was 1.7 hours)
• 24 IUD expulsions occurred in the immediate group compared to 2 in the delayed group
  • 19% vs 2%, P < .001

CONCLUSION:

• Results suggest that immediate postpartum IUD insertion is an acceptable option for women planning to breastfeed and use the levonorgestrel IUD
• Although expulsion rates are higher in immediate insertion, this is outweighed by the benefits of this technique

Learn More – Primary Sources:

Immediate postpartum levonorgestrel IUD insertion & breastfeeding outcomes: A noninferiority randomized controlled trial

IUD, Hysterectomy or Ablation for Menorrhagia?

BACKGROUND AND PURPOSE:

• Heavy menstrual bleeding accounts for 1/3 of gyn visits in the US
• Multiple treatment options exist when conservative medical therapy (e.g. oral contraceptives) are not sufficient for good control
• Spencer et al. (AJOG, 2017) evaluated the relative cost effectiveness of 4 possible treatments

METHODS:

• Researchers constructed a hypothetical cohort of 100,000 premenopausal women
• Researchers developed a decision tree which weighed a private payer cost with quality-adjusted life years (QALYs) over 5-years for women with heavy menstrual bleeding
• 4 treatment options
  • Hysterectomy
  • Resectoscopic endometrial ablation (REA),
  • Non-resectoscopic endometrial ablation (NREA)
  • Levonorgestrel-releasing intrauterine system (LNG-IUS)
• Each treatment option’s probabilities of minor complications, major complications, and treatment failure was derived from literature review
• Treatments were compared in terms of total average cost, total quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio

RESULTS:

• Compared to hysterectomy:
  • LNG-IUS had superior quality of life outcomes with lower costs
  • After analysis, LNG-IUS was more cost-effective in 90% of scenarios
  • Both REA and NREA had reduced costs, but lower average quality of life
  • Hysterectomy is associated with superior quality of life and fewer complications but more expensive than other treatments

CONCLUSION:

• Strong evidence that LNG-IUS is a cost-saving alternative to hysterectomy for heavy bleeding with comparable quality of life outcomes but reduced costs
• If LNG-IUS is not an option (patient choice or clinical reasons), decision is not as clear
  • Hysterectomy results in better quality of life and fewer complications than either type of ablation but at higher cost
  • Cost, potential complications and patient choice may drive decision

Learn More – Primary Sources:

Cost effectiveness of treatments for heavy menstrual bleeding

Managing Abnormal Uterine Bleeding with Ovulatory Dysfunction

CLINICAL ACTIONS:

Abnormal uterine bleeding in the setting of anovulation or oligoovulation (AUB-O) results from chronic estrogen stimulation of the endometrium. In the setting of irregular, prolonged bleeding (menorrhagia)

• Perform an age appropriate history and physical exam
• Appropriate lab tests include
  • Pregnancy test
  • Thyroid function tests
  • Prolactin level
  • PT/aPTT
  • Sexually transmitted disease testing
  • Complete blood count if bleeding is prolonged and heavy
• Endometrial biopsy should be performed in women over age 45 or those of any age with risk factors for endometrial hyperplasia or malignancy
  • Nulliparity, hypertension, obesity, irregular menses and family history of endometrial cancer
• Saline infusion sonohysterography (SIS), hysteroscopy or transvaginal ultrasound may be used to rule out an anatomic abnormality
• ACOG states that

Failure of medical management requires further investigation, including imaging or hysteroscopy

SYNOPSIS:

Ovulatory menstrual cycles generally occur between 21 and 45 days, are predictable, and last about 5 days reflecting sequential stimulation of the endometrium first by estrogen alone, then by a combination of estrogen and progesterone and finally by withdrawal of both hormones. The cause of AUB-O can be an abnormality at any level of the hypothalamic-pituitary-ovarian axis.  Consequences can include blood loss anemia due to heavy bleeding, as well as endometrial hyperplasia and endometrial cancer.

FIGO Subclassification System

The 4 types can be referred to by the acronym ‘HyPO-P’ | Last ‘P’ separated because it does not track to a single anatomic location

• Type 1: Hypothalamic
  • Genetic
  • Autoimmune
  • Iatrogenic
  • Neoplasm
• Type II: Pituitary
  • Functional
  • Infectious/Inflammatory
  • Trauma & Vascular
• Type III: Ovarian
  • Physiologic
  • Idiopathic
  • Endocrine
• Type IV: PCOS
  • Diagnosis and categorization and recommended by the International PCOS network

Note: According to FIGO, “The new system provides practical utility and a second layer, or sub-classification, for each of the three anatomically defined entities, including discrete pathophysiological categories. These can be remembered using the acronym ‘GAIN-FIT-PIE'”

KEY POINTS:

• The levonorgestrel IUD is effective in treating AUB-O and can be offered to all age groups
• Progestin and combination birth control pills are common medical options
• Weight loss and exercise should be strongly recommended for overweight anovulatory women
• Surgical therapy, such as hysterectomy, is rarely indicated but can be considered in women who have failed medical therapy or in whom medical therapy is contraindicated
• Hysterectomy with removal of the cervix can be offered to women who meet above criteria and have completed childbearing, or who have significant intracavitary pathology
• Endometrial ablation is not recommended as a first line therapy for AUB-O as traditional methods of endometrial surveillance may not be possible after the procedure
• ICD 10 code: N93.9

Learn More – Primary Sources:

ACOG Practice Bulletin 136: Management of Abnormal Uterine Bleeding Associated with Ovulatory Dysfunction

AAFP: Review of ACOG Practice Bulletin No. 136

FIGO: Ovulatory Disorders Classification System

Evaluation of Amenorrhea, Anovulation, and Abnormal Bleeding