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Cyclic fluctuations in human serum lipid and apolipoprotein levels during the normal menstrual cycle: comparison with changes occurring during oral contraceptive therapy.

The influence of menstrual cycle phases and hormonal contraception on serum lipid and apolipoprotein (apo) levels was investigated in a group of normally menstruating young women. The study period covered a normal menstrual cycle (pretherapy), the fourth cycle of treatment with a triphasic oral contraceptive (OC) preparation, and the cycle immediately following interruption of therapy (cycle 5, posttherapy). Cycle phases were defined on the basis of serum hormone levels and basal body temperature determinations. Significant differences in cholesterol (free and esterified) levels were observed during the menstrual phase of both the normal menstrual cycle (lower) and the OC cycle (higher), when compared with the other phases. Triglycerides, which were higher under OCs, fluctuated similarly throughout the two cycles, but phase differences did not reach statistical significance. Apo AI and apo B were both higher under OCs, and apo B followed a trend similar to cholesterol during the two cycles. During the first month after discontinuation of OCs, cholesterol levels returned progressively to baseline values, while triglycerides were only partially decreased. We conclude that cyclic fluctuations in lipid levels do occur under the influence of both endogenous and exogenous sex hormones.

Adult↗

Oral contraceptive steroid induced platelet coagulant hyperactivity: dissociation of in vivo and in vitro effects.

The use of oral contraceptives (OC) has been associated with an increased risk of thromboembolic events in a subset of women. Factors predisposing to this problem are still not clearly defined although an increased platelet coagulant activity (CA) has been reported. This study was designed to evaluate the CA of platelets from asymptomatic current OC users compared with control subjects. The asymptomatic OC users were found to have evidence of hypercoagulability in the form of increased availability of platelet CA. These findings were present in both collagen stimulated and unstimulated platelets. In order to understand the mechanism we examined the in vitro effects of estradiol and/or progesterone on platelets. Platelets from normal males were incubated for one hour with estrogen and/or progesterone. There was no significant difference in CA of hormone treated platelets compared with control platelets from the same donor. CA was analyzed in platelets exposed to epinephrine, adenosine diphosphate, and collagen in the platelet aggregometer. Although a dose dependent effect was observed on CA of platelets exposed to the range of aggregating agents, the results show no significant difference between CA of the hormone treated and control platelets (p greater than 0.05). Likewise, platelet aggregation and release of nucleotide were not different between hormone treated and control platelets. Thus a direct effect of the hormones on platelets is an unlikely mechanism causing the increased CA seen in OC users.

Adult↗

Return of ovulation after abortion and after discontinuation of oral contraceptives.

The return of ovulation after abortion and discontinuation of oral contraceptives was determined by plasma progesterone measurements. Plasma samples were obtained from 67 women at 3 to 6 weeks after abortion and in two groups of postabortion women at 3 to 6 weeks after cessation of oral contraceptives. In the first of these latter two groups, 50 women started taking the pills (containing 30 microgram of ethinylestradiol and 150 microgram of levonorgestrel) immediately after abortion, and the second group of 29 women started taking the pills from the first postabortion menses. Ovulation had recurred in 34% of the women 3 weeks after abortion and in 78% of the women at 6 weeks. The return of ovulation had occured in approximately 55% at 3 weeks after cessation of oral contraceptives in both groups. At 6 weeks after cessation, approximately 85% of women had ovulated in both groups. Luteal function in these two groups was found to be equal and was significantly better in both groups than during the first postabortion cycle (P < 0.005). It is concluded that the early return of ovulation after abortion makes it necessary to commence effective contraception immediately after abortion. The immediate administration of oral contraceptives after abortion does not affect the return of ovulation after discontinuation of oral contraceptives.

Abortion, Legal↗

Oral contraceptive oestrogen and progestin potencies and the incidence of deep venous thromboembolism.

To assess possible differences in the incidence of venous thrombosis and pulmonary embolism associated with oral contraceptives of varying hormonal potencies, the authors conducted a retrospective cohort study in the 15-44 year old Michigan Medicaid population. Cohorts were defined by the progestin- and oestrogen-potencies of oral contraceptives in use at the time of follow-up as classified by an oral contraceptive potency scheme. Using the low-oestrogen-/low-progestin-potency formulations for reference (rate ratio = 1), adjusted rate ratios of 0.8 (95% CI: 0.5 to 1.3, P = 0.41) and 0.6 (95% CI 0.4 to 1.2, P = 0.13) were observed for intermediate-progestin-potency and high-progestin-potency formulations, respectively. Adjusted rate ratios of 1.4 (95% CI: 0.8 to 2.3, P = 0.21) and 2.6 (95% CI: 1.2 to 5.5, P = 0.01) were observed for intermediate- and high-oestrogen-potency formulations. These data suggest a dose-response relationship between oral contraceptive oestrogen potency and venous thromboembolism, whereas no such evidence for a dose-response relationship between oral contraceptive progestin potency and venous thrombo-embolism was found.

Adolescent↗

Interference of gestagens and androgens with rat uterine oestrogen receptors.

The inhibitory effect of some gestagens and calusterone on the binding of oestradiol-17beta to its specific uterine receptors has been investigated in intact rats. Progesterone, medrogestone, clogestone, medroxyprogesterone acetate and calusterone reduce the specific oestradiol-receptor interaction in vitro; this effect is dose-dependent and does not differ significantly from one drug to the other. A more relevant decrease in the amount of oestradiol-17beta bound to specific receptors has been observed with calusterone. Progesterone, clogestone, medrogestone, medroxyprogesterone acetate and calusterone given orally induce a marked decrease (between 30 and 70% depending on the dose) in the binding capacity of oestradiol-17beta to specific uterine receptors in vivo. Results from a Scatchard plot analysis suggest that the interference with the binding of oestradiol-17beta caused by both progestogens and calusterone is due to a non-competitive interaction.

Animals↗

[The effect of different types of oral contraceptives upon ovarian function (author's transl)].

An investigation on the influence of different types of oral contraceptives upon serum gonadotropins, estradiol and progesterone was carried out in 10 volunteers. The effect of a change from a normophasic type preparation to a sequential preparation (Ovanon and Kombiquens) and from a combined preparation to a minipill (Neogynon and Exlutona) was studied. Two new 3-phase step-up preparations were also tested. Ovulation was inhibited in each case as the preovulatory LH-peak and the subsequent rise of serum progesterone were found to be missing. The basal LH- and FSH-secretion and serum estradiol were demonstrated to be significantly diminished in the volunteers taking combined and sequential preparations. The release of gonadotropines was not inhibited as much when the 3-phase step-up preparations (SHB 261 AB and SHB 264 AB) were used. When Exlutona was taken, the basal LH-secretion was lower than during the pre- and postovulatory phase of the normal cycle, but follicular development did not appear to be inhibited much as both FSH and estradiol were found to be in the normal range.

Adult↗

Suppression of ovarian function with the transdermally given synthetic progestin ST 1435.

OBJECTIVE: To study transdermal administration of the synthetic progestin ST 1435 and effectiveness of the steroid in suppression of ovarian function. DESIGN, PATIENTS: The effect of transdermal administration of the synthetic progestin ST 1435 in suppression of ovarian function was studied in a short term (17 to 93 days) study in healthy regularly menstruating women. SETTING: The outpatient clinic of the City Maternity Hospital, Helsinki, Finland. INTERVENTION: Nine women used the progestin ST 1435 transdermally during a total of 21 menstrual cycles. Treatment was started on the 5th day of the menstrual cycle and continued for 17 to 93 days. Three different daily doses (0.5, 0.8, and 1.0 mg) were tested. The steroid was applied to the periumbical area once a day in a gel. MAIN OUTCOME MEASURES: Serum concentrations of ST 1435, progesterone, and estradiol (E2) were determined during the luteal phase of control cycles and in a total of 16 treatment cycles. Bleeding records were kept and side effects registered. RESULTS: Transdermal absorption of the progestin ST 1435 resulted in relatively constant serum concentrations in each subject, depending on the dose used. All doses caused changes in ovarian function. With the 0.5-mg/d dose, inhibition of ovulation was observed in three of five treatment periods. The 0.8-mg/d dose was high enough to inhibit ovulation in 7 of 10 cycles analyzed. With the 1.0-mg/d dose, the serum concentrations of the progestin were high, and anovulation was seen. Serum E2 concentrations were variable in all cases; occasional high peak values were seen, typical of progestin treatment. Bleeding control was variable; irregular bleeding was seen, especially in anovulatory cases. CONCLUSIONS: A 0.8-mg dose of the progestin ST 1435 administered transdermally once a day appeared to suppress ovulation, if properly applied, and excessive suppression of ovarian function was not seen. The steroid was well accepted. The synthetic progestin ST 1435 given transdermally represents an effective alternative for inhibition of ovulation and for progestin therapy.

Administration, Cutaneous↗