Androgen Responses to hCG and Ovarian Morphology in PCOS
Status:
Unknown status
Trial end date:
2020-03-31
Target enrollment:
Participant gender:
Summary
Rationale and Hypothesis We have previously reported that theca cells (TC) responses to hCG
in women with PCOS represent a spectrum where some exhibit exaggerated increases of 17OHP
while in others 17OHP responses resemble those of normal women (Maas KH et al, JCEM, 2015).
The basis for this differential responsiveness is not clear. Earlier studies reported that
17OHP responses to gonadotropin stimulation were heterogeneous among PCOS women, which was
attributed to the degree of hyperinsulinemia (Pasquali R et al, JCEM, 2007). However,
assessment of the ovary was omitted in the analysis. In preliminary studies, we have found
that in women with PCOS, insulin sensitivity was strongly correlated with insulin sensitivity
index as assessed by the method of Matsuda and DeFronzo (Diabetes Care, 1999). However, the
study lacked sufficient numbers. Further analysis of insulin sensitivity with respect to hCG
stimulated theca cell responses is warranted.
We have also examined 17OHP responses to hCG in relationship to antral follicle count and
anti-Müllerian hormone (AMH) in PCOS and normal women. In PCOS women, as expected, serum AMH
correlated with antral follicle count. However, TC responses in PCOS were inversely related
to AMH (Maas KH et al, JCEM, 2015). These novel observations suggested that in PCOS AMH
production may reflect redistribution of the follicle population. In human ovaries maximal
immunodetection of AMH is observed in small (< 4 mm) antral follicles followed by a rapid and
progressive decline until an absence of the protein by 8 mm (Weenen C et al, Mol Hum Reprod,
2004). This consideration raises the issue of whether normal AMH levels represent more
advanced follicle growth in some PCOS women compared with that of others with elevated AMH
levels. An increased stage of follicle development would be accompanied by increased TC
hyperplasia and may account for greater 17OHP responses to hCG stimulation. A comparison of
TC responses to hCG with ovarian morphology has not be done in women with PCOS.
Based on these findings, we hypothesize that in PCOS, heterogeneous TC responses to hCG
reflect differences in morphometric development of the follicle population. In addition, the
positive correlation between insulin sensitivity and TC responses to hCG suggest an effect of
hyperinsulinemia. We propose to investigate the relationship between theca cell responses to
hCG, follicle morphology, and insulin sensitivity before and following treatment with an
insulin lowering drug, metformin.