Primary Dysmenorrhea Induced Using Diethylstilbestrol and Oxytocin Induces Impaired Uterine Reactivity in Virgin...

Background/Objectives: Primary dysmenorrhea (DysP) is a prevalent gynecological condition characterized by painful uterine contractions. However, the underlying mechanism of action of dysmenorrhea has not been fully elucidated. This study aimed to standardize an animal model of dysmenorrhea using diethylstilbestrol and oxytocin to mimic pathophysiological mechanisms in female Wistar rats.

For the induction of dysmenorrhea, diethylstilbestrol (s.c.) and oxytocin (i.p.) were used.

The model effectively reproduced hypercontractility and impaired uterine relaxation. The in vivo evaluations demonstrated increased pain responses (DysP group = 119 ± 6.9; control group CG = 3.0 ± 1.0), which were partially attenuated by standard medications (scopolamine/dipyrone and ibuprofen). In vitro assays revealed greater contractile reactivity when compared to that in the control group, in the DysP group, using oxytocin (pEC₅₀ = 3.6 ± 0.2 and E_max = 145.1 ± 8.7; CG (pEC₅₀ = 3.1 ± 0.1 and E_max = 100%); KCl (DysP pEC₅₀ = 2.2 ± 0.1 and E_max = 164 ± 8.0); CG (pEC₅₀ = 1.8 ± 0.1) and PGF_2α (DysP pEC₅₀ = 7.4 ± 0.2 and E_max = 127.3 ± 15.6); CG (pEC₅₀ = 6.2 ± 0.1)), while the relaxation responses to isoprenaline and nifedipine were decreased compared to those in the CG. The model promoted an imbalance in oxidative stress by increasing malondialdehyde (MDA) levels and reducing the total antioxidant capacity (TAC) in the uterine tissue.

These findings suggest that the new virgin rat model is capable of replicating key aspects of the clinical features of DysP in humans and offers a valuable tool for studying its pathogenetic mechanisms and testing potential therapeutic agents.