Ulipristal (UPA) effects on rat ovaries: Unraveling follicle dynamics, ovulation inhibition, and safety implications for prolonged use.

Ulipristal (UPA), a selective progesterone receptor modulator, has both agonistic and antagonistic effects on progesterone receptors. UPA suppresses ovulation by inhibiting the luteinizing hormone (LH) surge from the pituitary gland; however, the direct effect of UPA on ovarian tissue remains poorly studied. In the present study, we examined the effects of UPA on the ovaries of rats. Rats were treated for 28 days with UPA, and the effects of UPA on ovarian tissue were examined histologically and the expression of antioxidant genes and cell death markers were also investigated. UPA treatment increased the number of primordial follicles at each treatment group, primordial follicles increased at all dose levels, but the size/magnitude of the effect decreased with the increasing dose. The number of primary and antral follicles tended to increase with increasing UPA levels. Furthermore, the decrease in primary follicle number could be attributed to the exhaustion of follicles, but the examination of proliferation markers, oxidative stress markers, and cell death markers revealed no remarkable toxic effects on ovarian tissues. These results suggest that UPA treatment promotes follicle development at each stage but inhibits ovulation by suppressing the LH surge, resulting in an increase in atretic follicles or unruptured luteinized cysts. These results suggest that UPA may not have both toxic effects on the ovary and a direct local effect on ovarian follicles, but we should be careful about the effects of prolonged UPA treatment in patients with uterine fibroids on their future fecundity.

Impact of diagnosis and treatment of uterine fibroids on quality of life and labor productivity: The Japanese online survey for uterine fibroids and quality of life (JOYFUL survey).

AIM: To investigate the impact of uterine fibroid diagnosis/treatment status on quality of life (QOL) and work productivity in women living in Japan. METHODS: Women aged 20-49 years who registered on Macromill were recruited via the opt-in method. They completed an online survey on demographic and uterine fibroid diagnosis/treatment status, 36-Item Short-Form Health Survey, Uterine Fibroid Symptom and Health-Related Quality of Life questionnaire (UFS-QOL), and World Health Organization Health and Work Performance Questionnaire. RESULTS: There were 4120 respondents: 1362 untreated, 249 with ongoing treatment, 449 with past treatment, 1030 with no uterine fibroids, and 1030 with unknown uterine fibroid status. A high proportion of women with ongoing treatment had moderate to severe uterine fibroid-like symptoms (symptom severity score of UFS-QOL ≥40 points), accompanied by reduced QOL. QOL was improved in women with past treatment. Uterine fibroids had a significant impact on physical and psychosocial aspects in the ongoing treatment group versus other groups. Using classification and regression tree analysis, anemia was identified as a plausible predictor of reduced QOL in the ongoing treatment group. Approximately 20% of women-even in groups other than the ongoing treatment group-experienced moderate to severe uterine fibroid-like symptoms. However, the diagnosis and treatment status of uterine fibroids had no clear impact on work productivity. CONCLUSIONS: Uterine fibroids, especially in association with anemia, were related to reduced QOL. Given that uterine fibroid-related reduced QOL is likely improved by appropriate treatment, women with uterine fibroid-like symptoms, such as menorrhagia, should be examined and treated.

Induction of adrenomedullin 2/intermedin expression by thyroid stimulating hormone in thyroid.

TSH is the important regulator of thyroid function but detailed molecular mechanisms have not been clarified. We first generated the iodine deficient (ID) rat in which goiter is induced by accelerated endogenous TSH secretion. The result of microarray analysis demonstrated markedly increased levels of adrenomedullin 2/intermedin (AM2/IMD) expression in the ID rat thyroid. AM2/IMD is a potent vasodilator. AM2/IMD mRNA expression was induced by TSH in a rat thyroid follicular cell line FRTL-5. Immunohistochemical analysis in human normal and Graves' disease thyroid revealed that AM2/IMD immunoreactivity was detected in follicular cells and more pronounced in Graves' disease. These results indicated that TSH induced AM2/IMD expression in the rat thyroid gland and it could locally work as a potent vasodilator, resulting in the expansion of thyroid inter-follicular capillaries. AM2/IMD could also contribute to facilitate thyroid hormone synthesis possibly via vasodilation effects and/or cAMP stimulating effects in the human thyroid gland.