Mariana Paulson1,2,3, Lena Sahlin2, Angelica Lindén Hirschberg1,3. 1. Division of Obstetrics and Gynecology, and. 2. Pediatric Endocrinology Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm 17177, Sweden. 3. Department of Obstetrics and Gynecology, Karolinska University Hospital, Stockholm 17176, Sweden.
Abstract
Context: Polycystic ovary syndrome (PCOS) is associated with increased risk of endometrial cancer. This is usually explained by chronic anovulation and deficient progesterone activity. However, the role of progesterone receptors (PRs) in endometrial proliferation is unclear. Objective: To evaluate PRs in relation to endometrial proliferation in women with PCOS. Design: Cross-sectional study and lifestyle intervention. Setting: Clinical and laboratory research unit at a university hospital. Participants: Twenty obese women with PCOS and 10 age- and body mass index-matched regularly menstruating controls. Intervention: Dietary management and physical exercise. Main Outcome Measures: Endometrial messenger RNA (mRNA) levels and immunostaining of the nuclear PRs A (PRA) and B (PRB), nongenomic progesterone receptor membrane component 1 (PGRMC1) and 2 (PGRMC2), and proliferation marker Ki67. Results: Before lifestyle intervention, mRNA expression of PRAB was lower while PRB was higher in proliferative endometrium of obese women with PCOS compared with controls (P < 0.05). After lifestyle intervention and weight loss, mRNA expression of PRAB was still low but PRB mRNA decreased and was not different to controls in proliferative endometrium (P < 0.01). The subgroup of PCOS women who remained anovulatory displayed higher protein levels of PRB, PGRMC1, PGRMC2 and of the proliferative marker Ki67 on cycle days 21 to 23 than controls (P < 0.05). In contrast, the subgroup of PCOS women with confirmed ovulation showed immunostaining, including Ki67, in secretory endometrium that was not different to controls, except for higher PRA (P < 0.05). Conclusions: Lifestyle intervention improves, but not fully restores PR expression and decreases proliferation in secretory endometrium of obese PCOS women.
Context:Polycystic ovary syndrome (PCOS) is associated with increased risk of endometrial cancer. This is usually explained by chronic anovulation and deficient progesterone activity. However, the role of progesterone receptors (PRs) in endometrial proliferation is unclear. Objective: To evaluate PRs in relation to endometrial proliferation in women with PCOS. Design: Cross-sectional study and lifestyle intervention. Setting: Clinical and laboratory research unit at a university hospital. Participants: Twenty obesewomen with PCOS and 10 age- and body mass index-matched regularly menstruating controls. Intervention: Dietary management and physical exercise. Main Outcome Measures: Endometrial messenger RNA (mRNA) levels and immunostaining of the nuclear PRs A (PRA) and B (PRB), nongenomic progesterone receptor membrane component 1 (PGRMC1) and 2 (PGRMC2), and proliferation marker Ki67. Results: Before lifestyle intervention, mRNA expression of PRAB was lower while PRB was higher in proliferative endometrium of obesewomen with PCOS compared with controls (P < 0.05). After lifestyle intervention and weight loss, mRNA expression of PRAB was still low but PRB mRNA decreased and was not different to controls in proliferative endometrium (P < 0.01). The subgroup of PCOSwomen who remained anovulatory displayed higher protein levels of PRB, PGRMC1, PGRMC2 and of the proliferative marker Ki67 on cycle days 21 to 23 than controls (P < 0.05). In contrast, the subgroup of PCOSwomen with confirmed ovulation showed immunostaining, including Ki67, in secretory endometrium that was not different to controls, except for higher PRA (P < 0.05). Conclusions: Lifestyle intervention improves, but not fully restores PR expression and decreases proliferation in secretory endometrium of obese PCOSwomen.