Premenstrual syndrome and inflammatory activity in adolescent Familial Mediterranean Fever

• English title: Premenstrual syndrome and inflammatory activity in adolescent familial Mediterranean fever

• First author: Nigar Aliyeva

• Journal: Rheumatology

• Reference: Rheumatology (Oxford). 2026:keag169. doi: 10.1093/rheumatology/keag169. Online ahead of print.

• PubMed link: https://pubmed.ncbi.nlm.nih.gov/41936095/

• Abstracted by: Dr. Catherine Grandpeix-Guyodo

Key points - Premenstrual syndrome and inflammatory activity in adolescent familial Mediterranean fever

1. Premenstrual syndrome (PMS) is less frequent in FMF patients treated with colchicine than in healthy controls.

2. In FMF patients, PMS is associated with higher disease activity, systemic inflammation, and poorer treatment adherence. PMS severity appears to be proportional to the level of inflammation.

3. Colchicine may prevent PMS by reducing inflammation, which could explain the lower prevalence of PMS in colchicine-treated FMF patients compared with controls.

Introduction

PMS is linked to hormonal fluctuations, but immunological and inflammatory mechanisms also seem to contribute to symptom expression. Cytokine fluctuations during the menstrual cycle and the direct activation of the pyrin inflammasome by steroid catabolites support a direct link between reproductive physiology and inflammatory pathways.

However, there are limited clinical data on PMS in adolescents with FMF, and on its association with disease activity or adherence to colchicine treatment.

Patients and methods

This was a prospective, single-center Turkish study comparing adolescents aged 12 to 18 years with and without FMF, focusing on PMS. Menarche had to have occurred at least 6 months earlier; cycles had to be regular and bleeding last fewer than 7 days. FMF patients were required to have two pathogenic MEFV variants. Disease activity score (AIDAI), number of attacks per month (1 versus several), and biological inflammatory markers were collected, along with an assessment of PMS severity (PMSS).

Results

Mean age in both groups was 16 years. Mean height was significantly lower in the FMF group, while weight did not differ. Half of the FMF patients had not experienced a flare in the previous 6 months. Among 40 adolescents with FMF treated with colchicine, only 45% had PMS, compared with 75% among 40 controls. The difference in dysmenorrhea prevalence was not statistically significant, but longer menstruation and heavier bleeding were reported in FMF patients (p<0.05). PMS was more frequent and more severe in controls than in FMF patients.

Among FMF patients, those with PMS had higher AIDAI scores and more frequent FMF attacks. Blood inflammatory markers were also higher in this group. A clear correlation was observed between attack frequency and PMS severity.

There was also an association between PMS frequency and poor adherence to colchicine treatment.

Discussion

PMS appears less frequent in FMF, but PMS symptoms increase with inflammation. This suggests that colchicine, by modulating inflammation, could reduce hormonal symptoms and thus decrease PMS frequency. PMS is also more common in FMF patients with poor adherence to colchicine.

During the menstrual phase, decreased estrogen and increased IL-6 have been shown to intensify inflammation, which aligns with the observation that menstruation can trigger FMF attacks. Colchicine could therefore attenuate inflammatory fluctuations and modulate PMS.

Regarding the higher frequency of heavy bleeding during menstruation in FMF patients, one hypothesis is repeated use of anti-inflammatory drugs.

This study has limitations, including the small cohort size and its single-center design.

Conclusion

PMS is less frequent in FMF patients treated with colchicine than in healthy controls. In FMF patients, PMS is associated with higher disease activity, systemic inflammation, and poorer treatment adherence. Colchicine may prevent PMS by reducing inflammation, which could explain the lower frequency of PMS compared with the control population.