What should I do if I experience no withdrawal bleeding after taking Ethinylestradiol (Ethinyloestradiol)/Cyproterone acetate (Cyproterone) for 21 days followed by a 7-day break?

From the Guidelines

If you've completed a 21-day course of Ethinylestradiol/cyproterone acetate and didn't experience withdrawal bleeding during your 7-day break, you should start your next pack as scheduled. Not having a withdrawal bleed doesn't necessarily indicate a problem or pregnancy, as suggested by the U.S. selected practice recommendations for contraceptive use, 2024 1. These hormone-free breaks sometimes don't trigger bleeding, especially if you have a thin uterine lining or if your body is adjusting to the medication.

Key Considerations

• If you've missed pills, taken them inconsistently, or had unprotected intercourse during this cycle, consider taking a pregnancy test for reassurance.
• If you experience unusual symptoms like severe abdominal pain, or if missed periods continue for several cycles, consult your healthcare provider.
• The withdrawal bleeding with hormonal contraceptives isn't a true period but rather a reaction to the hormone withdrawal, so its absence doesn't always indicate a medical concern as long as you've taken your pills correctly, according to the management of bleeding irregularities while using contraception 1.

Next Steps

• Continue with your scheduled contraceptive regimen unless you have concerns that necessitate a healthcare provider's evaluation.
• Be aware of your body's response to the medication and report any unusual symptoms or persistent changes in your menstrual pattern to your healthcare provider.
• Explore patient goals, including continued method use or method discontinuation, and discuss any concerns or preferences with your healthcare provider, as recommended by the U.S. selected practice recommendations for contraceptive use, 2024 1.

From the FDA Drug Label

If scheduled bleeding does not occur, consider the possibility of pregnancy. If the patient has not adhered to the prescribed dosing schedule (missed one or two active tablets or started taking them on a day later than she should have), consider the possibility of pregnancy at the time of the first missed period and perform appropriate diagnostic measures If the patient has adhered to the prescribed dosing schedule and misses two consecutive periods, rule out pregnancy.

If you have taken Ethinylestradiol/cyproterone acetate for 21 days and had a 7-day break without withdrawal bleeding, consider the possibility of pregnancy. Since you have only missed one period, perform appropriate diagnostic measures to rule out pregnancy, such as a pregnancy test 2.

From the Research

Absence of Withdrawal Bleeding

• The absence of withdrawal bleeding after taking Ethinylestradiol/cyproterone acetate for 21 days and a 7-day break may be related to the hormonal effects of the treatment 3.
• Cyproterone acetate/ethinylestradiol is known to reduce menstrual irregularities and improve cycle control in women with polycystic ovary syndrome (PCOS) 3.
• However, the study on Ethinylestradiol/drospirenone mentions that the incidence of intermenstrual bleeding decreased rapidly after the first cycle, but it does not specifically address the absence of withdrawal bleeding 4.

Pharmacokinetics and Hormonal Effects

• The pharmacokinetics of cyproterone acetate and ethinylestradiol have been studied, and it was found that trough levels of cyproterone acetate in the serum increased during a treatment cycle, reaching a steady-state around day 16 5.
• The study also found that total and free testosterone concentrations decreased during treatment cycles by about 39% and 62%, respectively, compared with the corresponding values measured prior to treatment 5.
• The hormonal effects of ethinylestradiol and cyproterone acetate may contribute to the absence of withdrawal bleeding, but the exact mechanism is not fully understood 5.

Clinical Experience and Cycle Control

• A review of clinical experience with estradiol in combined oral contraceptives found that bleeding irregularities were a common issue with earlier formulations, but more recent studies with multiphasic regimens have shown improved cycle control 6.
• The study on extended cycles with the combined oral contraceptive chlormadinone acetate 2 mg/ethinylestradiol 0.03 mg found that extended-cycle use was associated with decreases in skin problems, dysmenorrhoea symptoms, and withdrawal bleeding 7.
• However, the study does not specifically address the absence of withdrawal bleeding with Ethinylestradiol/cyproterone acetate, and more research is needed to understand the effects of this treatment on menstrual bleeding 7.