Multilevel model to assess sources of variation in follicular growth close to the time of ovulation in women with normal fertility: a multicenter observational study

Mikolajczyk RT, Stanford JB, Ecochard R. Multilevel model to assess sources of variation in follicular growth close to the time of ovulation in women with normal fertility: a multicenter observational study. Reproductive Biology and Endocrinology. 2008;6(1): 61.Background: To assess the amount of variability in ovarian follicular growth rate and maximum follicular diameter related to different centers, women and cycles of the same women in a multicenter observational study of follicular growth. Methods: Secondary analysis of a prospective cohort study from eight centers in Europe. There were 533 ultrasound examinations in 282 cycles of 107 women with normal fertility. A random effects model with center, woman and cycle as hierarchical units of variation was used to analyze mean follicular diameter on days preceding ovulation. Results: Follicular growth did not differ by center. There was homogenous growth across women and cycles, and the maximum follicular diameter before ovulation varied substantially across cycles but not across women. Many (about 40%) women had small maximum follicular diameter on the day before ovulation (<19 mm). Pre-ovulatory cycle length was not related to maximum follicular diameter. Conclusion: In normal fecundity, there is a substantial variation in maximum follicular diameter from cycle to cycle based on variation in the duration of follicular development, but the variation could not be explained by different characteristics of different women. Explanation of variation in follicular growth has to be found on the cycle level

Is Cortisol Excretion Independent of Menstrual Cycle Day? A Longitudinal Evaluation of First Morning Urinary Specimens

Background Cortisol is frequently used as a marker of physiologic stress levels. Using cortisol for that purpose, however, requires a thorough understanding of its normal longitudinal variability. The current understanding of longitudinal variability of basal cortisol secretion in women is very limited. It is often assumed, for example, that basal cortisol profiles do not vary across the menstrual cycle. This is a critical assumption: if cortisol were to follow a time dependent pattern during the menstrual cycle, then ignoring this cyclic variation could lead to erroneous imputation of physiologic stress. Yet, the assumption that basal cortisol levels are stable across the menstrual cycle rests on partial and contradictory evidence. Here we conduct a thorough test of that assumption using data collected for up to a year from 25 women living in rural Guatemala. Methodology We apply a linear mixed model to describe longitudinal first morning urinary cortisol profiles, accounting for differences in both mean and standard deviation of cortisol among women. To that aim we evaluate the fit of two alternative models. The first model assumes that cortisol does not vary with menstrual cycle day. The second assumes that cortisol mean varies across the menstrual cycle. Menstrual cycles are aligned on ovulation day (day 0). Follicular days are assigned negative numbers and luteal days positive numbers. When we compared Models 1 and 2 restricting our analysis to days between −14 (follicular) and day 14 (luteal) then day of the menstrual cycle did not emerge as a predictor of urinary cortisol levels (p-value &gt;0.05). Yet, when we extended our analyses beyond that central 28-day-period then day of the menstrual cycle become a statistically significant predictor of cortisol levels. Significance The observed trend suggests that studies including cycling women should account for day dependent variation in cortisol in cycles with long follicular and luteal phases

Future therapeutic targets in rheumatoid arthritis?

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by persistent joint inflammation. Without adequate treatment, patients with RA will develop joint deformity and progressive functional impairment. With the implementation of treat-to-target strategies and availability of biologic therapies, the outcomes for patients with RA have significantly improved. However, the unmet need in the treatment of RA remains high as some patients do not respond sufficiently to the currently available agents, remission is not always achieved and refractory disease is not uncommon. With better understanding of the pathophysiology of RA, new therapeutic approaches are emerging. Apart from more selective Janus kinase inhibition, there is a great interest in the granulocyte macrophage-colony stimulating factor pathway, Bruton's tyrosine kinase pathway, phosphoinositide-3-kinase pathway, neural stimulation and dendritic cell-based therapeutics. In this review, we will discuss the therapeutic potential of these novel approaches