CONTRACEPTION
AN
OPEN PROSPECTIVE STUDY ON THE EFFECTS ON CARBOHYDRATE METABOLISM OF AN ORAL MONOPHASIC CONTRACEPTIVE CONTAINING GESTODENE (WL-70) G.F.Trossarelli, R.Bordon, G.L.Gennarelli and Q.Carta* Department of Gynecology and Obstetrics, Chair A (Chief:A.Bocci), University of Turin *San Giovanni Hospital of Turin Italy
ABSTRACT The effects of a monophasic oral contraceptive (gestodene 75mcg + ethinylestradiol 30mcg) on plasma glucose (PG) and insulin (IRI) responses to an oral glucose load (OGTT) and on glycosylated haemoglobin Ale (HbAlc), fructosamine (Fr), total cortisol (FT) and transcortin (CBG) were studied in 30 healthy women. Blood samples were taken before treatment and after 6 and 12 cycles. After 6 and 12 months, OGTT-PG and IRI levels showed substantially unchanged values; forHbAlcand Fr the same behaviourwas seen withtheexception of the latter between 6 and 12 months; FT and CBG showed significant rises. All recorded values were in the normal range. The basal and dynamic PG and IRI behaviour failed to show any significant variations between pre-treatment values and those after 6 and 12 months of OC administration. Other data showed a substantial neutrality for this oral contraceptive containing gestodene.
INTRODUCTION The use of oral contraceptives (OCs) has been associated with alterations in carbohydrate metabolism (l-7) since the publication, in 1963, of Waine's paper (8). However the changes in glucose homeostasis, referred to in the literature, are moderate and return to baseline once OCs are discontinued (1). The influence of natural and synthetic estrogens on glucose tolerance is little, if any. Estrogens have been demonstrated to have direct stimulus on beta-cell insulin secretion thereby increasing total cortisol. Submitted for publication June 20, 1990 Accepted for publication February 28, 1991
MAY 1991 VOL. 43 NO. 5
423
CONTRACEPTION
The latter modification is mainly due to the estrogen-induced rise in the synthesis of liver transcortin (CBG), so that the free and metabolically active cortisol fraction is nearly unchanged. Both progesterone and progestogens seem to have a beta-cytotropic effect (6,7,9) and induce a reduction in the peripheral sensitivity to insulin (lO,ll,lZ). Spellacy et al. (13,14,15) clearly demonstrated that some progestogens may induce a worsening in carbohydrate metabolism; this adverse effect may be partly due to the androgenic activity of synthetic steroids derived from 19-nortestosterone. Gestodene (GSD), synthetized by Hofmeister in 1975, is a derivative of 19-nortestosterone and differs from levonorgestrel in that carbons 15 and 16 of the furan ring present a double bond. The consequent steric configuration considerably heightens the molecule's affinity for progesterone receptors and gives a weak antialdosterone activity (16). This property allowed its dosage to be reduced by half in relation to the other hormonal contraceptives. The aim of this study was to evaluate glucose and insulin responses to an oral glucose load before and during the administration of a monophasic OC preparation containing GSD.
METHODS Study design: A longitudinal study of carbohydrate metabolism before and after 6 and 12 months of low dosage OC treatment (WI-70, Wyeth) with ethinylestradiol (EE) 30 mcg and GSD 75 mcg. age 2621.2 years Subjects: 30 normal menstruating women, mean (range: 17-39), weight ranging from 42 to 72.5 Kg (mean Body Mass Index (BMI) = 21.820.6; 83% of the study group had a BMI
AN
OPEN PROSPECTIVE STUDY ON THE EFFECTS ON CARBOHYDRATE METABOLISM OF AN ORAL MONOPHASIC CONTRACEPTIVE CONTAINING GESTODENE (WL-70) G.F.Trossarelli, R.Bordon, G.L.Gennarelli and Q.Carta* Department of Gynecology and Obstetrics, Chair A (Chief:A.Bocci), University of Turin *San Giovanni Hospital of Turin Italy
ABSTRACT The effects of a monophasic oral contraceptive (gestodene 75mcg + ethinylestradiol 30mcg) on plasma glucose (PG) and insulin (IRI) responses to an oral glucose load (OGTT) and on glycosylated haemoglobin Ale (HbAlc), fructosamine (Fr), total cortisol (FT) and transcortin (CBG) were studied in 30 healthy women. Blood samples were taken before treatment and after 6 and 12 cycles. After 6 and 12 months, OGTT-PG and IRI levels showed substantially unchanged values; forHbAlcand Fr the same behaviourwas seen withtheexception of the latter between 6 and 12 months; FT and CBG showed significant rises. All recorded values were in the normal range. The basal and dynamic PG and IRI behaviour failed to show any significant variations between pre-treatment values and those after 6 and 12 months of OC administration. Other data showed a substantial neutrality for this oral contraceptive containing gestodene.
INTRODUCTION The use of oral contraceptives (OCs) has been associated with alterations in carbohydrate metabolism (l-7) since the publication, in 1963, of Waine's paper (8). However the changes in glucose homeostasis, referred to in the literature, are moderate and return to baseline once OCs are discontinued (1). The influence of natural and synthetic estrogens on glucose tolerance is little, if any. Estrogens have been demonstrated to have direct stimulus on beta-cell insulin secretion thereby increasing total cortisol. Submitted for publication June 20, 1990 Accepted for publication February 28, 1991
MAY 1991 VOL. 43 NO. 5
423
CONTRACEPTION
The latter modification is mainly due to the estrogen-induced rise in the synthesis of liver transcortin (CBG), so that the free and metabolically active cortisol fraction is nearly unchanged. Both progesterone and progestogens seem to have a beta-cytotropic effect (6,7,9) and induce a reduction in the peripheral sensitivity to insulin (lO,ll,lZ). Spellacy et al. (13,14,15) clearly demonstrated that some progestogens may induce a worsening in carbohydrate metabolism; this adverse effect may be partly due to the androgenic activity of synthetic steroids derived from 19-nortestosterone. Gestodene (GSD), synthetized by Hofmeister in 1975, is a derivative of 19-nortestosterone and differs from levonorgestrel in that carbons 15 and 16 of the furan ring present a double bond. The consequent steric configuration considerably heightens the molecule's affinity for progesterone receptors and gives a weak antialdosterone activity (16). This property allowed its dosage to be reduced by half in relation to the other hormonal contraceptives. The aim of this study was to evaluate glucose and insulin responses to an oral glucose load before and during the administration of a monophasic OC preparation containing GSD.
METHODS Study design: A longitudinal study of carbohydrate metabolism before and after 6 and 12 months of low dosage OC treatment (WI-70, Wyeth) with ethinylestradiol (EE) 30 mcg and GSD 75 mcg. age 2621.2 years Subjects: 30 normal menstruating women, mean (range: 17-39), weight ranging from 42 to 72.5 Kg (mean Body Mass Index (BMI) = 21.820.6; 83% of the study group had a BMI
