Thompson expanded on that point, noting that “not all patients with PMOS are overweight and in fact there is a phenotype of thin patients who do not neatly fit into the classic presentation.”
“PMOS is a spectrum of symptoms and for patients who are affected at the milder end of the spectrum diet and lifestyle interventions may be enough to be helpful in managing their condition,” she advised.
Both Thompson and Vasilev stressed that only individuals with both overweight or obesity and PMOS are the most likely to benefit from a GLP-1 treatment.
“The strongest data [regarding GLP-1s for PMOS] are in overweight/obese women,” Vasilev reiterated.
He also emphasized that there are several situations in which individuals with PMOS who might otherwise benefit from GLP-1 treatment would be best advised to try a different route.
Firstly, he said, anyone looking to conceive should avoid GLP-1s. These drugs “are ‘teratogenicity-concern’ agents, which means that they must be stopped before conception,” said Vasilev.
“This is a major caveat in a population where many patients are actively seeking fertility; contraception and preconception discontinuation counseling are required,” he advised.
He also outlined the importance of gastrointestinal adverse effects such as nausea, vomiting, and dizziness, that can come with GLP-1 use. These adverse effects “are common and should not be taken lightly,” cautioned Vasilev.
Moreoever, “tirzepatide’s delayed gastric emptying can reduce oral contraceptive efficacy, which is relevant when pregnancy prevention matters,” he told us, adding that “this represents a big caution flag.”
Finally, Vasilev explained that since there is currently no definitive proof that GLP-1s are a potent treatment for PMOS due to “low to very low” certainty evidence derived from “small and heterogeneous” clinical trials, other treatments remain the preferred first-line of action.
Thus, he said:
“Guideline positioning still focus[es] on lifestyle optimization, combined oral contraceptives for menstrual/androgenic symptoms, and metformin for metabolic features; GLP-1 RAs are not [an] established first-line [treatment for PMOS]. Well-designed, PMOS-specific, phenotype-stratified trials are needed before that changes.”
