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Many patients undergoing second-trimester abortion or pregnancy loss experience breast symptoms that are both physically and emotionally painful. A recent Stanford Medicine ÌÇÐÄ´«Ã½ study tested a one-time dose of cabergoline to decrease the frequency and severity of these symptoms.

"Historically, the majority of abortion ÌÇÐÄ´«Ã½ has focused on access," saidÌý, clinical assistant professor of obstetrics and gynecology and principal investigator for the trial. "Less emphasis has been placed on the experience around abortion care and perinatal loss. Often, we’re thankful we can get people the care they need at all, and we think less about what aftercare looks like."

The history of cabergoline for lactation inhibition
Most people who experience pregnancy loss in the second trimester develop breast symptoms such as engorgement and milk leakage. Whether patients have chosen not to become parents or experienced a tragedy, these lactation-related symptoms are often physically uncomfortable, undesired, and upsetting.ÌýÌý

Historically, in the United States, dopamine agonists such as bromocriptine were prescribed for postpartum lactation inhibition. In the 1990s, reports of postpartum stroke led to a medication black box warning from the Food and Drug Administration. Although there was never an established causal relationship between bromocriptine and stroke, nothing has been officially on the market for lactation inhibition for more than two decades.

In other developed countries, doctors have used cabergoline for lactation inhibition for several years. The adoption of its use in the U.S. has been spearheaded by HIV/AIDS advocacy. Because more people with HIV are surviving longer, more are giving birth but are instructed not to breastfeed. In 2020, the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) recommended cabergoline for lactation inhibition in people who are HIV-positive. Their recommendation was based on the substantial safety and efficacy data associated with cabergoline around the world. Since then, some abortion providers in the U.S. have been using cabergoline off-label.

Designing the cabergoline clinical trial
Dr. Henkel and her team designed a study to methodically assess cabergoline’s efficacy and potential side effects. Over an enrollment period of 18 months, the study screened 150 patients, enrolled 73, and obtained completed surveys from 69.

Participation was open to those who were:

• Older than 18 years old
• At 18 to 28 weeks of gestation
• Seeking elective abortion care or stillbirth induction
• English- or Spanish-speaking

Exclusion criteria included:

• Contraindications to cabergoline
• Currently breastfeeding
• Currently receiving dopamine agonist therapy for other indications
• History of cardiac valvular disorders or valvular repair
• History of pulmonary, pericardial, or retroperitoneal fibrotic disorders
• Prior mastectomy (including breast reduction or chest masculinization surgery)
• Uncontrolled hypertension, chronic hypertension requiring more than one baseline medication, or pregnancy-induced hypertension spectrum disorders

Trial results show cabergoline efficacy
The double-blinded, block-randomized superiority trial gave patients 1 milligram cabergoline or an identical placebo at the time of treatment. Researchers collected symptom data at the time of treatment and on days 2, 4, 7, and 14 post-procedure. A subset of patients returned for serum lab draws to measure prolactin levels.

Patients reported breast symptoms using the Bristol Breast Symptoms Inventory. This inventory evaluates the four domains of breast symptoms, including:

• Engorgement
• Milk leakageÌý
• Need for pain relief
• Tenderness

At baseline, breast symptoms were similar between the two groups. However, the returned surveys on day 4 showed that only 27.8% of participants who received cabergoline reported breast symptoms, compared to 97% of those in the placebo group. Only 2.8% of those in the cabergoline group reported significant bother compared to 33.3% in the placebo group. Significantly, these differences persisted through the 14-day period after the procedure.

"It was challenging to power this study, because we weren’t sure how many people were impacted by breast symptoms," Dr. Henkel explained. Although ÌÇÐÄ´«Ã½ers have long known that most people who experience second-trimester uterine evacuation have breast symptoms, it had not been studied in a methodologically rigorous manner. "Our results found that significantly more people experience breast symptoms than we realized," Dr. Henkel added.

Importantly, side effects were rare but similar between the cabergoline and placebo groups. Fewer people reported hot flashes or significant bother from side effects in the cabergoline group. "Breast engorgement is hard and awful for many people," Dr. Henkel said. "It’s very reassuring to see that this one-time dose was well-tolerated with no significant side effects."

Future innovations and improvements in care
Currently, Dr. Henkel is launching clinical trials to evaluate the efficacy of cabergoline given at 16 to 18 weeks and 18 to 20 weeks of gestation. Most freestanding abortion clinics treat patients up to 20 weeks of gestation. Data for the efficacy of cabergoline between 16 to 20 weeks would offer abortion providers an official option for breast symptom management in these patients.

"The trial is an acknowledgement that a loss at this point in pregnancy, whether through abortion or fetal demise, has ongoing impact beyond the day of the procedure," Dr. Henkel said. "As clinicians, there’s so much space for us to innovate and improve those patients’ experiences. We still need to be asking what their experience is like after they leave the hospital."

ÌÇÐÄ´«Ã½ encourages you to share information about thisÌýÌýwith your patients.Ìý