Female adolescents and adults with sickle cell disease are at risk for a range of menstrual complications, especially pain and abnormal uterine bleeding.

That’s according to the authors of a new multi-center survey study which found “a high rate of menstruation-related pain in female patients with sickle cell disease, which was associated with high healthcare use and minimal use of hormonal contraception.” The study was authored by Neha Bhasin, MD, and her colleagues. 

The study was published online in JAMA Network Open.

A pediatric hematologist-oncologist at Benioff Children’s Hospital at the University of California, San Francisco, Bhasin directs the Pediatric Comprehensive Center for Sickle Cell Disease there.

To identify hospitalization rates of menstruating women and adolescents with sickle cell disease and to determine their level of access to reproductive health interventions, Bhasin et al developed a cross-sectional survey and distributed it across 13 outpatient sickle cell disease treatment centers. 

The survey was administered from March 1, 2022, through May 31, 2024, to menstruating women between the ages of 12 and 54 who had experienced at least one episode of menstrual bleeding in the previous 12 months (no pregnant or post-menopausal women) and who had any sickle cell disease genotype. 

Bhasin and her colleagues used the age-appropriate Menstrual Bleeding Questionnaire to assess menstrual patterns. Participants were also given study-specific surveys about their sickle cell disease health and contraceptive use. After these results were analyzed, the investigators also surveyed the participants’ clinicians for their patients’ clinical history and care plans. 

Of 211 patients, 208 (mean age of 23.7) completed the Menstrual Bleeding Questionnaire. Of these, 148 had sickle cell hemoglobin (HbS) (70.1%), and 38 (17.9%) had HbSC disease. There were six (2.8%) with HbS beta-0 and 18 (8.5%) with HbS beta+ genotypes. Lastly, one person had an “other” genotype. 

There were 183 (86.8%) sets of patient-facing surveys with a corresponding clinician survey. Fifty-two (24.6%) questionnaire respondents, including 41 of 141 adults (29.1%) and 12 of 71 (16.9%) adolescents, had abnormal uterine bleeding based on their menstrual questionnaire score of 24 or greater (P = .08). These scores were not significantly different among the genotypes, but abnormal uterine bleeding was associated with higher rates of hospitalization in the past 6 months. 

In particular, 18 women with abnormal bleeding had zero hospitalizations (40.9%), 24 (54.5%) had 1-3 hospitalizations, and two (4.5%) had four hospitalizations. That’s compared with the group with no abnormal bleeding of which had 91 (65.5%) had zero hospitalizations, 38 (27.3%) had 1-3 hospitalizations, and 10 (7.2%) had four hospitalizations (P = .004).

Of the 208 respondents, 134 (64.4%) described experiencing extreme sickle cell pain at the time of their menses. Once again, there was no significant difference in responses among genotypes, and those who described sickle cell pain had higher menstrual bleeding scores (SD, 19.6 [11.2%] vs 13.4 [6.9%] responding no; P < .001). 

The heavy pain cohort had a greater number of emergency department visits (P = .003) and hospitalizations (P = .001) than those who did not have pain at the time of menstruation. More adults (96 of 137 [70.1%]) than adolescents (38 of 69 [55.1%]) reported sickle cell pain (P < .03).

Most patients reported taking disease-modifying therapies for at least 6 months prior to survey completion. Of 154 patients with HbSS and HbSO, 119 were taking hydroxyurea (77.3%), eight of 208 patients (3.8%) were taking crizanlizumab, 24 of 208 (11.5%) were taking voxelotor, and 11 of 208 (5.3%) were taking L-glutamine.

Forty of 208 (19.2%) participants reported using hormonal contraception, with 15 of 40 (37.5%) reporting taking it specifically for period-related pain or sickle cell pain, while 11 of 40 (27.5%) reported using it for pregnancy prevention. Nearly half of those using hormonal contraception (19 of 40 [47.5%]) reported receiving it from a gynecologist (21 of 40 [52.5%]) or a combination of primary care practitioners, adolescent medicine practitioners, hematologists, or others. 

Twenty-one clinicians completed the survey. Ferritin levels at less than 50 ng/mL were noted in 13 participants (12.3%). Low hemoglobin and high total bilirubin, reticulocyte counts, and absolute neutrophil counts were not associated with higher menstrual bleeding scores or greater sickle cell pain around menstruation. Low hemoglobin was associated with more emergency department visits and hospital admissions.

“What is novel about our study is it was across multiple centers, and then also that we found menstrual bleeding or abnormal uterine bleeding was associated with high healthcare utilization,” Bhasin told Medscape Medical News. “[The women] had higher ED visits and hospital admissions because of their pain.”

Bhasin also said that the study was the first to examine the interventions clinicians are prescribing to this patient population, if any. “I wanted to bring attention to this for sickle cell providers. To say, ‘Menstrual history is important to do.’” Healthcare utilization and pain is related to menstruation, she said.

In an accompanying editorial, Tolulope O. Rosanwo, MD, a pediatrician specializing in sickle cell anemia and a fellow at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, wrote, “Menstruation is not often considered a cause of vaso-occlusive crisis possibly because the mechanism behind this phenomenon is not well understood.”

“To provide menstruating patients with sickle cell disease the best care, primary care physicians, gynecologists, and hematologists need to be educated about the association between menstruation and vaso-occlusive crisis and share that this may be a concern as adolescents start menstruating,” Rosanwo also wrote. 

“Early referral to a gynecologist to discuss menstrual management options is always a good idea as anemia can be worsened from abnormal uterine bleeding as well,” Tambu Kudze, MD, MHS, a pediatric and adolescent gynecologist and assistant professor at the University of Washington and the Seattle Children’s Hospital, told Medscape Medical News.

“Hormonal management options can be reviewed and the patient’s goals, cultural considerations, and concerns can be taken into account.” Seeing a gynecologist early on, even prior to menarche provides an opportunity for education about menstrual issues unique to sickle cell patients early on before they have worsened, causing anemia, need for emergency room visits, and poor quality of life,” Kudze said. 

 

Rosanwo reported receiving a patent for “Compositions and Methods for Red 

Blood Cell Differentiation” licensed to The Children’s Medical Center Corporation. Bhasin had no disclosures. Kudze had no disclosures.