Microg Ethinyl Research Articles

A prospective study evidencing rhinomanometric and olfactometric outcomes in women taking oral contraceptives.

The aim of this prospective study was to evaluate the changes in olfactory sensitivity of oral contraceptive (pill) users. Sixty women underwent rhinomanometric and olfactometric determinations during the follicular, periovular and luteal phases of the menstrual cycle, and at day 7, 14 and 21 of contraceptive intake. Thirty-one women used 30 microg ethinyl oestradiol plus 75 microg gestodene and 29 women used 20 microg ethinyl oestradiol plus 150 microg desogestrel. Rhinomanometry showed higher but not statistically significant values during the periovular phase than in the follicular and luteal phases. Olfactometry showed a higher sensitivity during the follicular and periovular phases than during the luteal phase of the menstrual cycle. The rhinomanometric surveys in pill users were statistically different from those of the luteal phase (P < 0.02) and the follicular and periovular phases (P < 0.001). The olfactometric thresholds during the period of contraceptive use were statistically different from those of the follicular phase for a few odorous substances, and from those of the periovular phase for each odorous substance, but similar to those of the luteal phase (P = NS). Unlike the rhinomanometric airflow and trans-nasal pressure, the olfactory threshold to odours seems to depend on the variations of the ovarian steroids during the menstrual cycle and on the iatrogenic effects of oral contraceptives.

Oral contraceptive use and hormone replacement therapy are associated with microalbuminuria.

Controversy exists regarding the adverse and beneficial effects of oral contraceptive use and hormone replacement therapy. Microalbuminuria is associated with increased risk of renal and cardiovascular disease. To examine the association between oral contraceptive use or hormone replacement therapy and microalbuminuria. We performed a case-control study of the baseline data and historical pharmacy data of 4301 female subjects of the Prevention of Renal and Vascular End Stage Disease study cohort, aged 28 to 75 years, excluding women who were pregnant or had type 1 diabetes mellitus. The main outcome measure was microalbuminuria, defined as a urinary albumin excretion of 30 to 300 mg per 24 hours (recorded as the mean of two 24-hour urine collections). After adjusting for age, hypertension, diabetes, obesity, hyperlipidemia, and smoking, the odds ratio (OR) for having microalbuminuria was 1.90 (95% confidence interval [CI], 1.23-2.93) for premenopausal oral contraceptive users and 2.05 (95% CI, 1.12-3.77) for postmenopausal hormone replacement therapy users. The point estimate increased in a dose-dependent fashion, albeit insignificantly, according to the estrogen content of the oral contraceptives (<30 microg ethinyl estradiol: OR, 1.11; 95% CI, 0.14-8.56; 30 to <50 microg: OR, 1.83; 95% CI, 1.17-2.87; and 50 microg: OR, 2.72; 95% CI, 0.81-9.08). The OR was greater in oral contraceptives with a second-generation (OR, 2.04; 95% CI, 1.28-3.25) vs a third-generation progestin (OR, 1.39; 95% CI, 0.63-3.06). The OR increased with the duration of hormone replacement therapy (< or =5 years, OR, 1.28; 95% CI, 0.37-4.50; >5 years, OR, 2.56; 95% CI, 1.32-4.97). Regular and long-term oral contraceptive use and hormone replacement therapy are associated with an increased risk for microalbuminuria and cardiovascular disease.

Low-dose oral contraceptives: protective effect on ovarian cancer risk.

Low-dose oral contraceptive (OC) formulations containing 35 microg or less ethinyl estradiol have preferably been prescribed in the last decade, however, few data exist on its relation to ovarian cancer risk. We determined the effects of low-dose OC on the risk of ovarian cancer in a population-based case-control study, including 282 patients ages 20-75 years at diagnosis of incident primary invasive ovarian cancer or borderline tumour between 1993-1996 and 533 control subjects individually matched by age and study area to each case. Analysis excluded women who had undergone a bilateral ovariectomy or had a previous diagnosis of either ovarian cancer or borderline tumour. The association of OC use by ethinyl estradiol dose and ovarian cancer risk was assessed by odds ratios (OR), adjusting simultaneously for the other OC types and determinants of ovarian cancer risk. Ovarian cancer risk was significantly reduced by 52% for ever use of any type of OC. The reduction in risk was 7% per year of use (OR = 0.93, 95% confidence interval [CI] = 0.90-0.96) and was more evident in first-use subjects younger than 25 years. Risk reduction for ovarian cancer was substantial for use of low-dose OC, the odds ratios being 0.86 (95% CI = 0.77-0.94), 0.91 (95% CI = 0.83-1.00), and 0.95 (95% CI = 0.91-0.99) per year of using OC containing <35 microg, 35-<50 microg, and >or=50 microg ethinyl estradiol, respectively. Our study provides evidence that low-dose oral contraceptives confer substantial protection against the development of ovarian cancer.

Permanent effects of neonatal estrogen exposure in rats on reproductive hormone levels, Sertoli cell number, and the efficiency of spermatogenesis in adulthood.

This study aimed to identify the mechanism(s) for impairment of spermatogenesis in adulthood in rats treated neonatally with estrogens. Rats were treated (days 2-12) with 10, 1, or 0.1 microg diethylstilbestrol (DES), 10 microg ethinyl estradiol (EE), 10 mg/kg of a GnRH antagonist (GnRHa), or vehicle and killed in adulthood. DES/EE caused dose-dependent reductions in testis weight, total germ cell volume per testis, and Sertoli cell volume per testis. Sertoli cell number at 18 days of age in DES-treated rats was reduced dose dependently. GnRHa treatment caused changes in these parameters similar to those in rats treated with 10 microg DES. Plasma FSH levels were elevated (P < 0.001) to similar levels in all treatment groups regardless of differences in Sertoli cell number and levels of inhibin B; the latter reflected Sertoli cell number, but levels were disproportionately reduced in animals treated with high doses of DES/EE. Neonatal estrogen treatment, but not GnRHa, caused dose-dependent reductions (40-80%) in plasma testosterone levels in adulthood, but did not alter LH levels. Preliminary evidence suggests that the decrease in testosterone levels in estrogen-treated rats is not due to reduced Leydig cell volume per testis. GnRHa-treated rats exhibited a significant increase in germ cell volume per Sertoli cell and a reduction in germ cell apoptosis, probably because of the raised FSH levels. Despite similar raised FSH levels, rats treated with DES (10 or 1 microg) or EE (10 microg) had reduced germ cell volume/Sertoli cell and increased germ cell apoptosis, especially when compared with GnRHa-treated animals. The latter changes were associated with an increase in lumen size per testis, indicative of impaired fluid resorption from the efferent ducts, resulting in fluid accumulation in the testis. Rats treated neonatally with 0.1 microg DES showed reduced germ cell apoptosis comparable to that in GnRHa-treated animals. The changes in apoptotic rate among treatment groups occurred across all stages of the spermatogenic cycle. It is concluded that 1) neonatal estrogen treatment results in dose-dependent alterations in Sertoli cell numbers, germ cell volume, efficiency of spermatogenesis, and germ cell apoptosis in adulthood; 2) the relatively poor spermatogenesis in estrogen-treated animals is most likely due to altered testis fluid dynamics and/or altered Sertoli cell function; 3) as indicated by FSH (LH) and testosterone levels, the hypothalamic-pituitary axis and Leydig cells are probably more sensitive than the Sertoli cells to reprogramming by estrogens neonatally; and 4) elevated FSH levels in adulthood may improve the efficiency of spermatogenesis.

Contraceptive efficacy and acceptability of a monophasic oral contraceptive containing 30 microg ethinyl estradiol and 150 microg desogestrel in Latin-American women.

Contraceptive efficacy, subject acceptability (cycle control, side-effects, acne score and weight gain) and blood pressure of a monophasic oral contraceptive containing 30 microg ethinyl estradiol plus 150 microg desogestrel (Marvelon) were assessed in an open-label 6-cycle multicenter study in Argentina (7 centers) and Venezuela (5 centers). Of the 407 participating women, 389 (95.6%) completed six cycles of treatment, providing data for a total of 2383 cycles. No pregnancies occurred during the course of the study, confirming the high contraceptive reliability of Marvelon. Cycle control was excellent; the duration of withdrawal bleeding decreased during consecutive treatment cycles and the incidence of spotting and breakthrough bleeding was low. The desogestrel/ethinyl estradiol combination was well tolerated and the incidence of minor side-effects, which was already low in the first treatment cycle, in most cases decreased during the subsequent cycles. The preparation was effective in reducing pre-existing acne, whereas it did not induce clinically relevant changes in blood pressure and body weight. Marvelon was shown to provide effective oral contraception, with good tolerance and excellent cycle control in Latin-American women.

Comparison of spironolactone-oral contraceptive versus cyproterone acetate-estrogen regimens in the treatment of hirsutism

To compare the efficacy of two antiandrogens, cyproterone acetate (CPA) and spironolactone, in the treatment of hirsutism. Prospective randomized single-blinded study. A tertiary hirsutism clinic. Forty-two premenopausal patients with hirsutism were selected. Subjects were randomized to receive either 100 mg spironolactone and an oral contraceptive (OC) containing 150 microg desogestrel and 30 microg ethinyl E2 or 50 mg CPA daily on days 1 to 10 of the menstrual cycle, which was administered with 35 microg ethinyl E2 daily on days 1 to 21. Hirsutism scores were measured according to Ferriman-Gallwey scoring system and side effects were monitored for 9 months of treatment. Blood samples were taken at each visit for assessment of endocrine, biochemical, and hematologic parameters. Hirsutism scores were decreaded significantly in both groups at the end of 9 months. The percent of change in hirsutism scores in CPA and spironolactone group were as follows: 19.23% +/- 14.77% and 24.48% +/- 14.27% at 3 months; 39.01% +/- 19.77% and 37.46% +/- 16.90% at 6 months; and 51.89% +/- 20.87% and 46.39% +/- 16.10% at 9 months, respectively. There was a trend toward a better response with CPA treatment, which did not achieve significance. None of the patients stopped treatment because of side effects. The present data suggest that both spironolactone and CPA were similarly effective in treatment of hirsutism.

A bioequivalence study of two urinary follicle stimulating hormone preparations: Follegon and Metrodin

The purpose of this study was to demonstrate bioequivalence between two follicle stimulating hormone (FSH)-only gonadotrophin preparations (Follegon(R) and Metrodin(R)) after a single i.m. injection of IU FSH in-vivo bioactivity. A total of 16 healthy normally cycling females were treated for 7 weeks with a high-dose oral contraceptive containing 50 microg ethinyl oestradiol plus 2.5 mg lynestrenol (Lyndiol(R)) to suppress endogenous gonadotrophin production. After 3 and 5 weeks or oral contraceptive treatment, each subject received 300 IU Follegon or Metrodin in a random order. Frequent blood sampling was performed to measure immunoreactive FSH for pharmacokinetic analysis. After normalization for the immunodose administered, Follegon and Metrodin were bioequivalent with respect to the extent and the rate of absorption, the elimination half-life and plasma clearance per kg. The time taken to reach peak plasma FSH concentrations was shorter with Follegon than with Metrodin. Because bioequivalence was proved for the major pharmacokinetic variables, it can be assumed that Follegon and Metrodin are also equally effective inovulation induction, in-vitro fertilization and embryo transfer programmes and the treatment of male infertility.