G. B. Melis

A comparative study on the effects of a monophasic pill containing desogestrel plus 20 μg ethinylestradiol, a triphasic combination containing levonorgestrel and a monophasic combination containing gestodene on coagulatory factors

The changes in haemostasis during oral contraception are related to the ethinylestradiol dose present in the formulation taken by the patient. An open, randomized longitudinal study was performed to evaluate and compare the effects that low-dose oral contraceptives (OCs) containing different doses of ethinylestradiol exert on the haemostatic system. Eighty-nine healthy women, aged 18-45 years, were randomly assigned to treatment with 3 different OCs: a monophasic pill containing 30 micrograms of ethinylestradiol plus 75 micrograms of gestodene (GSD/30) (30 subjects), a triphasic pill containing levonorgestrel (TRI/LNG) (28 subjects), a monophasic pill containing 20 micrograms ethinylestradiol plus 150 micrograms of desogestrel (DOG/20) (31 subjects). From every woman, blood samples were collected before treatment and at the 3rd and 6th cycle of pill intake. The number of platelets significantly increased (p less than 0.01) during treatment with TRI/LNG. Fibrinogen plasma values were significantly increased (p less than 0.05) only in women treated with the preparation GSD/30. Fibrinopeptide A (FPA) plasma levels significantly increased (p less than 0.01) during treatment with the pills TRI/LNG and GSD/30, but the levels of FPA were unchanged in the group treated with DOG/20. The overall results of this study confirm that the effects of OCs on haemostasis are dependent on the ethinylestradiol dose. Moreover, they suggest that with reduction of the ethinylestradiol component to 20 micrograms, the effects of OCs on haemostasis seem to be virtually eliminated.

Effects of different dopamine agonists and antagonists on post-menopausal hot flushes

The dopaminergic system seems to be involved in both pulsatile luteinizing hormone (LH) secretion and hot flushes in post-menopausal women. With the aim of further clarifying its role, the effectiveness of dopaminergic and antidopaminergic drugs in the treatment of hot flushes was studied. Self-assessed scores for vasomotor symptoms were evaluated in 5 groups of 15 patients treated for 20 days with one of the following agents: placebo; the dopamine receptor agonist, bromocriptine; the indirect dopaminergic agent, Liposom; the antidopaminergic drug, veralipride or the peripheral antidopaminergic agent, domperidone. All of these treatment regimens were effective in alleviating hot flushes, but the pharmacological agents proved to be more effective than the placebo. A direct dopaminergic action is hypothesized in the case of bromocriptine and Liposom, while the antidopaminergic drugs might act through different indirect mechanisms such as the short-loop feedback exerted by hyperprolactinaemia on tuberoinfundibular dopamine (TIDA) neurons with a secondary dopamine-like activity, or stimulation of the opioid system.

Effects of continuous and cyclic nasal calcitonin administration in ovariectomized women.

The aim of the present study was to assess the effects of continuous and cyclic salmon calcitonin (sCT) administration in the prevention of the rapid bone loss that follows ovariectomy in humans. Patients who had undergone bilateral ovariectomy 10-30 days previously received either calcium supplementation alone (500 mg/day, n = 12) or such supplementation together with nasal sCT (200 IU/day) according to a continuous (n = 20) or a cyclic (3 months on, 1 month off) regimen (n = 16) for 2 years. In the calcium-only-treated subjects urinary hydroxyproline excretion, serum alkaline phosphatase and plasma bone Gla protein levels showed a substantial increase (P < 0.01) 6 months after surgery, while radial bone density was found to have decreased significantly (P < 0.01). The patterns of biochemical markers in the sCT-treated groups indicated that nasal sCT can positively uncouple the two bone remodelling processes without inducing any significant change in radial bone density over a 2-year period. No differences were observed between the two sCT-treated groups. These results demonstrate that the rapid bone loss that follows ovariectomy can be prevented by either cyclic or continuous nasal sCT administration. Thus, cyclic nasal sCT represents an attractive alternative for the prevention of osteoporosis in postmenopausal women with contraindications to oestrogen replacement therapy.

METABOLIC EFFECTS OF THREE NEW LOW-DOSE PILLS : A SIX-MONTH EXPERIENCE

We evaluated the effects on glucose and lipid metabolism in 57 healthy volunteers randomly assigned to one of three low-dose oral contraceptives: two monophasic (desogestrel + ethinylestradiol, EE, and cyproterone acetate + EE) and one triphasic (gestodene + EE) contraceptives. Glucose and insulin responses during OGTT were slightly affected by the cyproterone pill. The insulin area/glucose area ratio and HbA1c level were unchanged in all women. No preparation affected total and LDL-cholesterol levels. Triglycerides rose in all groups, while HDL-CH did only in women taking the two monophasic pills. The three low-dose pills assessed in this study have negligible effects on glucose and lipid metabolism.

Fibrinopeptide a plasma levels during low-estrogen oral contraceptive treatment

In a group of healthy women taking oral contraceptives containing 30 micrograms ethinylestradiol combined with two different progestogens (desogestrel and gestoden), Fibrinopeptide A (FPA) plasma levels were evaluated both before and after 3, 6 and 9 months of therapy. FPA levels, which represent an index of thrombin action in vivo, were also determined in untreated subjects during the follicular and the luteal phases of the menstrual cycle. While no modifications of FPA levels were found during the menstrual cycle, a significant increase of this peptide was observed during oral contraceptive treatment. These data suggest that low-dose oral contraceptives, by enhancing the rate of conversion of fibrinogen to fibrin by thrombin, increase the risk of venous thrombosis. Since some mechanisms which compete with the thrombin activity are also increased by oral contraceptives, the significance of this change in the induction of thrombosis cannot be completely clarified.

Oral contraceptives and venous thromboembolic disease: the effect of the oestrogen dose

Low-dose oral contraceptives when tested for vascular or thrombotic effects not only show no risk of venous thromboembolic disease, but this method could possibly reduce the chance of thromboembolic disease as compared with pills which have a higher estrogen dose. It has also been found that pills containing lower doses of estrogen have no effect on the coagulatory system. Concerns raised about the connection between oral contraceptive use and the risk of cardiovascular disease called for testing in the late 1960s. Epidemiological studies confirmed the risk of oral contraceptive use and cardiovascular disease especially venous thromboembolism. A further association was identified between the amount of estrogens contained in oral contraceptives and the risk of disease. Estrogens affect the hemostatic system; decreases in antithrombin III activity in addition to platelet adhesiveness and blood viscosity have been observed in oral contraceptive users. Although both a decreased influence on the hemostatic system and the risk of thromboembolic disease have been found in pills with lower doses of estrogen, further research on the effect of the clotting system by low-dose oral contraceptives is needed.

Interaction between veralipride and the endogenous opioid system in the regulation of body temperature in postmenopausal women

Abstract The influence of endogenous opioid peptides on body thermoregulation has been studied in untreated postmenopausal women and in the same subjects after chronic administration of the antidopaminergic drug veralipride (200 mg/day for 20 days). Subjects randomly received an infusion of the opioid antagonist naloxone (1.6 mg/h for 4 h) or saline on two consecutive days, both before and after ceralipride treatment. In untreated subjects body core temperature, as evaluated by rectal temperature, did not vary during saline infusion, whereas a significant decrease was observed during naloxone infusion. Chronic administration of veralipride significantly increased thenhypothermic response to naloxone. Therefore, veralipride seems to increase the activity of endogenous opioid peptides on mechanisms which regulate body temperature in postmenopausal women.

Prolactin-Releasing Action of a Low Dose of Exogenous Gonadotropin-Releasing Hormone Throughout the Human Menstrual Cycle

Pharmacological doses of gonadotropin-releasing hormone (GnRH) are known to induce prolactin (PRL) release in different pathological states. The same effect can be observed in postmenopausal women and during the phases of menstrual cycle characterized by high estrogen levels. With the aim to evaluate whether nonpharmacological doses of GnRH are also able to induce PRL release, gonadotropin and PRL response to a low dose of GnRH (10 micrograms, i.v. bolus) was evaluated in 70 normal women during different phases of their menstrual cycle. A significant PRL increase was observed in 33% of subjects during the first days of the cycle (menstrual phase; days 1-3 from the beginning of menstrual bleeding: n = 6), in 24% of subjects during early follicular phase (days -10 to -8 from LH peak: n = 17); in 38% of subjects during midfollicular phase (days -6 to -4 from LH peak: n = 8); in 78% of subjects during preovulatory phase (days -2 to -1 from LH peak; n = 9); in 67% of subjects during postovulatory phase (days +1 to +2 from LH peak; n = 6) and in 42% of subjects during midluteal phase (days +5 to +8 from LH peak; n = 24). In brief, the increase of mean PRL levels after GnRH administration was only significant (p less than 0.05) during pre- and postovulatory phases. The percentage of patients who showed a PRL response during the different phases of menstrual cycle was significantly correlated to the mean maximal net increase of LH (r = 0.927; p less than 0.01) and to the mean maximal net increase of FSH (r = 0.926; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Regulation of body temperature in postmenopausal women: interactions between bromocriptine and the endogenous opioid system

The role exerted by the endogenous opioid system on thermoregulation has been studied in nine postmenopausal women before and after the chronic administration of the dopamine agonist bromocriptine (5 mg/day). These women randomly received an infusion of the opioid antagonist naloxone (1.6 mg/h for 4 h) or saline on two consecutive days, before and after 30 days of bromocriptine administration. Body temperature as evaluated by rectal temperature, did not vary during saline infusion performed both before and after 30 days of bromocriptine administration. In untreated women naloxone infusion significantly reduced body core temperature. The hypothermic response to naloxone was significantly greater following chronic bromocriptine administration. These results indicate that bromocriptine seems to increase the activity of the endogenous opioid system on the mechanisms which regulate body temperature in postmenopausal women.

Effect of desogestrel-containing oral contraceptives on vascular reactivity and catecholamine levels

The modifications induced by new oral contraceptives (OC) on blood pressure, great vessel vascular reactivity by color Doppler, and catecholamine levels were investigated. Young healthy women not taking OC (n = 22; controls) or receiving, for > or = 6 months, OC containing desogestrel with either 30 micrograms (n = 14) or 20 micrograms of EE (n = 8) were enrolled. Blood pressure measured at rest in supine position was similar between controls and OC users. The pulsatility index (PI), an indirect index of resistance to blood flow, of axillary artery was significantly higher (p < 0.05) in 30 micrograms than in 20 micrograms EE OC users or controls. A similar trend, albeit not significant, was observed for the internal carotid artery PI. Norepinephrine (p < 0.01) and dopamine (p < 0.05) but not epinephrine levels, were lower in 30 micrograms EE OC users than in 20 micrograms EE OC users or controls. Thus, both 20 micrograms and 30 micrograms EE OC had no negative effect on blood pressure, but the 30 micrograms EE OC tended to increase great vessel resistance to blood flow, independently of catecholamine levels.