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Divergent Effects of Weight Reduction and Oral Anticonception Treatment on Adrenergic Lipolysis Regulation in Obese Women with the Polycystic Ovary Syndrome¹

Department of Medicine, Research Center, and Department of Gynecology and Obstetrics (I.E., K.C., A.B.), Huddinge University Hospital, Karolinska Institute, S-141 86 Huddinge, Sweden

Address all correspondence and requests for reprints to: Hans Wahrenberg, M.D., Center of Metabolism and Endocrinology, Department of Medicine M63, Huddinge Hospital, Karolinska Institute, S-141 86 Huddinge, Sweden.

The influence of weight reduction and female sex hormones on the regulation of lipolysis was investigated in isolated abdominal sc adipocytes from 20 obese hyperandrogenic women with polycystic ovary syndrome (PCOS). Nine PCOS women were reinvestigated after 8–12 weeks of weight reduction therapy (WR) with a very low calorie diet, inducing a mean loss of 8 ± 3 kg, and 8 PCOS women were reinvestigated after 12 weeks of treatment with combined oral contraceptives (OC), containing ethinyl estradiol and norethisterone; the remaining 3 subjects were drop-outs. Both WR and OC normalized hyperandrogenicity.

WR caused a 50% reduction of basal lipolysis rate and a 5- to 7-fold increased noradrenaline and terbutaline sensitivity (P < 0.02); the latter could be ascribed to a 2-fold increased ß₂-adrenoceptor density (P < 0.02) as determined with radioligand binding. There was no change with regard to dobutamine (ß₁-adrenoceptor sensitivity) or clonidine, (₂-adrenoceptor sensitivity) or to ß₁-adrenoceptor density. OC treatment did not influence the basal lipolysis rate or ß₂- or ₂-adrenoceptor sensitivity, but lowered the ß₁-adrenoceptor sensitivity 7-fold (P < 0.03) without a reduction in ß₁-adrenoceptor density. The OC treatment effect was not observed when forskolin and dibutyryl cAMP, acting on adenylate cyclase or protein kinase A, respectively, were used, suggesting a partial uncoupling of ß₁-adrenoceptors. WR therapy, but not OC therapy, caused, in addition to changes in lipolysis function, improved in vivo insulin sensitivity and lower plasma noradrenaline levels. These findings suggest that factors other than hyperandrogenicity modulate lipolysis regulation in obese subjects with PCOS. Disturbances in sympathetic pathways could be of pathogenic importance.

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