Suppression of ovarian function by a combined oral contraceptive containing 0.02 mg ethinyl estradiol and 2 mg chlormadinone acetate given in a 24/4-day intake regimen over three cycles

Objective

To describe the suppression of ovarian function with 0.02 mg ethinyl E₂–2 mg chlormadinone acetate administered in a 24/4-day intake regimen in healthy women.

Design

Open, uncontrolled, multiple dosing, phase II trial.

Setting

Single clinic.

Patient(s)

Forty women treated.

Intervention(s)

Treatment for up to three cycles with 0.02 mg ethinyl E₂–2 mg chlormadinone acetate given in a 24/4-day regimen.

Main Outcome Measure(s)

Assessments of ovarian function classified by the Hoogland and Skouby score, thickness of endometrium, cervical reaction, and sex hormone levels, as well as overall tolerability.

Result(s)

No ovulation was observed in the per protocol set (N = 36), and one in the full analysis set (N = 38) after vomiting and diarrhea. Absence of ovarian activity, residual ovarian activity, and formation of a luteinized unruptured follicle were observed in 75.0%, 15.9%, and 1.1% of medication cycles, respectively. Endometrial thickness was suppressed to 4 to 5 mm compared with 10 to 12 mm without medication. Cervical reaction was negative. Hormone levels were lower with medication than without, and the medication was well tolerated. Treatment-related adverse events were typical of those associated with hormonal contraceptive use.

Conclusion(s)

Follicular development, cervical reaction, and endometrial thickness were suppressed profoundly after 0.02 mg ethinyl E₂–2 mg chlormadinone acetate administration in a 24/4-day regimen, resulting in inhibition of ovulation and unfavorable conditions for fertilization, implantation, and thus pregnancy.

Key Words: Combined oral contraceptive, oral contraception, low-dose ethinylestradiol, chlormadinone acetate, 24/4-day intake regimen, ovarian activity, ovarian function