Doris Heger-Mahn

A randomised study comparing the effect on ovarian activity of a progestogen-only pill (POP) containing desogestrel and a new POP containing drospirenone in a 24/4 regimen

Abstract Objectives Progestogen-only pills (POPs) are safer with respect to cardiovascular risks than contraceptives containing estrogens. Despite the increased contraceptive efficacy of a desogestrel-only pill compared with a traditional POP, POPs are still not widely used due to an unpredictable bleeding pattern. A new POP containing 4 mg drospirenone has been developed with a 24/4 intake regimen which may improve the bleeding pattern. The objectives of this study were to investigate ovulation inhibition with the new drospirenone-only pill in comparison with the desogestrel-only pill and, in addition, to assess the effects on cervical mucus permeability and bleeding. Methods Sixty-four healthy volunteers with proven ovulatory cycles were randomised and treated with either the drospirenone-only or the desogestrel-only pill during two 28-day cycles. Follicular diameter, endometrial thickness, and serum estradiol (E2) and progesterone concentrations were measured and Hoogland scores were determined. Additionally, cervical mucus scores, bleeding and return of ovulation were assessed. Results Both treatments effectively inhibited ovulation. Follicular diameter, E2 levels and Hoogland scores were equal, demonstrating efficient ovarian suppression. One subject in each group had a Hoogland score of 6, but the criteria for normal luteal activity were not fulfilled. In both groups, ovulation did not occur before day 9 of the post-treatment cycle. Cervical mucus permeability was suppressed in both groups. The median number of bleeding and spotting days was lower in the drospirenone group. Conclusions The new drospirenone-only pill inhibited ovulation as effectively as the desogestrel-only pill despite the 4-day hormone-free interval. Chinese Abstract 摘要 目的 对于心血管疾病风险，纯孕激素避孕药比含雌激素的避孕药安全。尽管只含去氧孕烯的避孕药与传统纯激素避孕药相比，避孕效果增加了，由于不可预知的出血模式，纯孕激素避孕药仍没有被广泛应用。包含4毫克屈螺酮的新型纯孕激素避孕药已被研制出，采用24/4方案可以改善出血模式。这项研究的目的是调查仅含屈螺酮的新型避孕药与仅含去氧孕烯的避孕药相比对排卵抑制的情况，此外，也用于评估对宫颈粘液穿透性和出血的影响。 方法 经过验证有排卵周期的64名健康志愿者，在两个28天的周期中被随机给予仅含屈螺酮或者去氧孕烯的避孕药。测定卵泡直径、子宫内膜厚度、血清雌二醇和孕激素浓度，并进行Hoogland评分。此外，对宫颈粘液评分、出血及排卵抑制进行评估。 结果 两种治疗方法都能有效的抑制排卵。卵泡直径、雌二醇水平和Hoogland评分都是相同的，以及证明有效的排卵抑制。每组每一项的Hoogland评分都是6，但是黄体活动的标准还没有制定。在预处理周期的第9天以前，两个组都不会出现排卵。两个组的宫颈粘液穿透性都被抑制了。在屈螺酮组中，黄体期出血天数的中位数比较低。 结论 尽管有4天无激素的时间间隔，仅含屈螺酮的新型避孕药与仅含去氧孕烯的避孕药对排卵的抑制效果是一样的。 关键词 去氧孕烯片；去氧孕烯；屈螺酮；卵巢活动；排卵抑制；纯孕激素型避孕药

Short-term treatment with levonorgestrel does not antagonize the ethinyl estradiol-induced increase of uterine blood flow in postmenopausal women

The aim of this study was to determine the effect of a short-term ethinyl estradiol/levonorgestrel medication on blood flow in the uterine arteries in postmenopausal women in a prospective placebo-controlled double-blind study. Twenty-one healthy postmenopausal woman at least 2 years after menopause received 60 micrograms ethinyl estradiol (EE) for 14 days followed by 40 micrograms EE plus 125 micrograms levonorgestrel (LNG) for 12 days (total treatment period 26 days). Sonographically, uterine volume, endometrial thickness, and blood flow in the uterine arteries [as reflected by pulsatility (PI) and resistance indices (RI)] were measured. Uterine size increased from 44 to 80 mL (day 14, p < 0.001) and 87 mL (day 26, p = NS). Endometrium grew from 3 to 8 mm (day 14, p < 0.001) and 11 mm (day 26, p = NS). Uterine arterial PI fell from 2.76 to 1.37 (day 14, p < 0.001) and 1.34 (day 26, p = NS), whereas RI fell from 0.9 to 0.68 (day 14 and day 26, p < 0.001). In conclusion, short-term treatment with LNG does not antagonize the vascular effect of EE on the uterine arteries as reflected by PI and RI. This result might have clinical significance in the selection of the progestin used in hormonal replacement therapy.

Phase II dose-finding study on ovulation inhibition and cycle control associated with the use of contraceptive vaginal rings containing 17β-estradiol and the progestagens etonogestrel or nomegestrol acetate compared to NuvaRing

Abstract Purpose: To identify at least one contraceptive vaginal ring that effectively inhibits ovulation and demonstrates cycle control that is non-inferior to NuvaRing® (Merck Sharp & Dohme B.V., The Netherlands) in terms of an unscheduled bleeding incidence, with a non-inferiority margin of 10%. Methods: This was a randomised, active controlled, parallel group, multicentre, partially blinded trial in healthy women 18–35 years of age. Subjects received one of six contraceptive vaginal rings with an average daily release rate of 300 µg 17β-estradiol (E2) and various rates of either etonogestrel (ENG; 75, 100, or 125 µg/day) or nomegestrol acetate (NOMAC; 500, 700, or 900 µg/day), or the active control NuvaRing® (ENG/ethinylestradiol 120/15 µg), for three 28-day cycles. Results: Ovulation inhibition was observed in all groups as confirmed by absence of progesterone concentrations compatible with ovulation (>16 nmol/L) and absence of ultrasound evidence of ovulation. All investigational rings provided good cycle control, with the ENG-E2 125/300 µg/day group being associated with the best cycle control based on the numerically lowest incidence of unscheduled bleeding and absence of scheduled bleeding. Non-inferiority to NuvaRing® with respect to the incidence of unscheduled bleeding could not be concluded for any of the investigational ring groups. The safety profile was consistent with the known safety profile of combined estrogen/progestin contraceptives and similar across all groups. Conclusions: Contraceptive rings releasing 300 µg E2 and 75–125 µg/day of ENG or 500–900 µg/day of NOMAC provided adequate ovulation inhibition and cycle control and are generally well-tolerated. While non-inferiority to NuvaRing® was not met, among the investigational rings, the ENG-E2 125/300 ring provided the best cycle control.

Suppression of ovarian activity with a low-dose 21/7-day regimen oral contraceptive containing ethinylestradiol 20 mcg/drospirenone 3 mg in Japanese and Caucasian women ☆

BACKGROUND Two studies assessed the effect of a low-estrogen-dose 21/7-day oral contraceptive containing ethinylestradiol and drospirenone (EE 20 mcg/drsp 3 mg) on ovarian activity in Japanese and Caucasian women. STUDY DESIGN Study 1 was conducted in Japanese women (20-35 years), and Study 2 was conducted in Caucasian women (18-35 years). All women received EE 20 mcg/drsp 3 mg in a 21-day active pill regimen. The primary endpoint was the proportion of women with ovulation inhibition (Hoogland score <6; as assessed by transvaginal ultrasonography) during treatment cycle 2. RESULTS Japanese (n=23) and Caucasian (n=30) women received two cycles of study treatment. During treatment cycle 2, ovulation was inhibited in 100% and 92.9% of Japanese and Caucasian women, respectively. CONCLUSIONS EE 20 mcg/drsp 3 mg in a 21/7-day regimen provides comparable ovarian suppression in Japanese and Caucasian women, with normal ovarian function resuming shortly after treatment end in both populations.