BALTIMORE — Use of a combined GLP-1/GIP receptor agonist was associated with improved menstrual regularity, an analysis of a prospective cohort showed.
Women taking the combination incretin drug had a reduction in cycle length of 2.5 days compared with a reduction of 0.4 days for those on a GLP-1 drug and 0.8 days for never-users, reported Shruthi Mahalingaiah, MD, MS, of the Harvard T.H. Chan School of Public Health in Boston, and colleagues.
The combined GLP-1/GIP receptor agonist also was associated with a more pronounced decrease in mean individual cycle variability, at 6.93 days compared with 7.45 days for GLP-1 drugs and 7.46 days for never-users, they reported during a presentation at the American Society for Reproductive Medicine (ASRM) annual meeting.
Furthermore, a subgroup analysis of patients with polyendocrine metabolic ovarian syndrome (PMOS; formerly polycystic ovary syndrome [PCOS]) showed even more marked effects. For this group, mean individual cycle variability was 5.80 days for combined GLP-1/GIP receptor agonist users, 7.34 days for GLP-1 receptor agonist users, and 9.45 days for never users, they reported.
“This more pronounced reduction among PMOS individuals might suggest a separate pathway that might focus on ovulatory health in addition to those metabolic parameters that support ovulation, but further research is necessary,” Mahalingaiah said.
Rachel Weinerman, MD, an ob/gyn and reproductive endocrinologist at Case Western Reserve University in Cleveland who wasn’t involved in the study, told MedPage Today that this study’s findings about PMOS were particularly interesting.
“We know that because PMOS is a metabolic issue, weight loss can actually help patients achieve a more regular cycle,” she said. Thus, when a PMOS patient is on a weight-loss medication, it makes sense that they would both lose weight and have more regular periods, she noted.
Weinerman added that irregular periods aren’t only problematic for people trying to get pregnant; they can signal underlying health issues. This study is a good reminder that PMOS patients are a distinct group who may respond to medications differently than others with similar characteristics, she said.
More than 10 million women in the U.S. use either a GLP-1 or combined GLP-1/GIP receptor agonist, which work through different mechanisms of action (the only GLP-1/GIP drug approved by the FDA is tirzepatide [Zepbound]). These therapies may impact ovulatory health through systemic and metabolic health improvements or direct ovarian impacts, Mahalingaiah noted.
While some retrospective studies have suggested an association with improved menstrual regularity, no prospective studies have looked at it as a primary endpoint. So this research sought to determine if these agents were associated with changes in mean cycle length and cycle variability in tracked menstrual cycles.
“We wanted to show, with a little more granularity, the extent to which we might see impact,” Mahalingaiah told MedPage Today.
Researchers utilized the Apple Women’s Health Study (AWHS), which is a longitudinal digital cohort of about 147,000 U.S. women and their prospectively logged menstrual cycles. Patients are 18 and older, have an iPhone, and have menstruated at least once. Participants in this analysis were younger than 50, could not be using hormones or be pregnant or lactating, and had a cycle length between 10 and 90 days. They had to have logged at least 3 cycles.
Mahalingaiah and team ultimately analyzed 1,945 participants with 70,134 logged cycles; most (1,564) were never-users while 258 used a GLP-1 medication and 123 used a combined GLP-1/GIP medication in the past year.
This cohort responded to surveys with questions about weight-loss medications, demographics, and medical history. They also consented to share their logged menstrual information recorded on HealthKit, though authors did not use any sensor-based data.
Researchers stratified groups by those who indicated using a GLP-1 or combined GLP-1/GIP receptor agonist in the past year and those who hadn’t, as well as those with and without PMOS. Baseline characteristics were similar between groups, though medication users veered older (age 38 to 39 vs 35) and had higher parity than never-users. They also had a higher proportion of PMOS, infertility, type 2 diabetes, and hypertension.
The primary reason for being prescribed a GLP-1 or GLP-1/GIP receptor agonist in the past year was weight loss for health, followed by weight loss for appearance and PMOS.
Mahalingaiah noted that future manuscripts will break down this data by particular agents.
“There is such little innovation in women’s health pharmaceuticals that maybe data like this could help people in pharma think about the additional mechanisms that might promote ovulation,” Mahalingaiah said.
