Why does ethinylestradiol (EE)/cyproterone acetate (CPA) not regulate menstrual cycles?

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From the Guidelines

Ethinylestradiol/cyproterone acetate does not regulate menstrual cycles because it suppresses natural menstruation entirely, creating artificial withdrawal bleeding rather than true menstruation. This combination medication, commonly known as Diane-35 or similar brand names, contains synthetic estrogen (ethinylestradiol) and an anti-androgen (cyproterone acetate) that work together to prevent ovulation and maintain relatively constant hormone levels, thereby suppressing the normal hormonal fluctuations of the menstrual cycle 1. The bleeding that occurs during the pill-free interval is not a true menstrual period but rather withdrawal bleeding caused by the temporary drop in hormone levels.

The primary use of ethinylestradiol/cyproterone acetate is to treat androgen-dependent conditions like acne, hirsutism, and polycystic ovary syndrome, rather than for menstrual regulation. Key points to consider include:

  • The medication prevents the normal development of follicles, ovulation, and the natural rise and fall of estrogen and progesterone.
  • It maintains relatively constant hormone levels that suppress the hypothalamic-pituitary-ovarian axis.
  • The risks associated with the use of combined oral contraceptives (COCs), such as venous thromboembolic events, myocardial infarction, and stroke, must be weighed against the benefits of treatment for acne and other androgen-dependent conditions 1.
  • For patients specifically seeking menstrual cycle regulation, other hormonal contraceptives with different hormone combinations might be more appropriate.

In terms of the mechanism of action, COCs like ethinylestradiol/cyproterone acetate decrease androgen production at the level of the ovary and increase sex hormone-binding globulin, binding free circulating testosterone and rendering it unavailable to bind and activate the androgen receptor 1. This antiandrogenic effect is beneficial for the treatment of acne and other androgen-dependent conditions. However, for menstrual regulation, the constant hormone levels and suppression of natural menstrual cycles may not be ideal.

From the Research

Menstrual Regulation

  • Ethinylestradiol/cyproterone acetate does regulate menstrual irregularities, as stated in the study 2, which found that it provides effective treatment for polycystic ovary-related hyperandrogenic skin symptoms, and also treats menstrual irregularities and reduces endometrial cancer risk.
  • The study 3 also mentions that one of the additional benefits of cyproterone acetate/ethinyl estradiol is cycle control, which implies that it can help regulate menstrual cycles.
  • Another study 4 states that the combination of cyproterone acetate and ethinyl estradiol is of proven efficacy in the management of symptoms of both hyperandrogenism and menstrual abnormalities.

Evidence Against Non-Regulation

  • There is no evidence in the provided studies to suggest that ethinylestradiol/cyproterone acetate does not regulate menstrual irregularities. In fact, all the studies that mention menstrual regulation suggest that it has a positive effect on it 2, 3, 4.
  • The study 5 does not mention menstrual regulation, but it does discuss the efficacy of cyproterone acetate/ethinyl estradiol in treating acne, which is a related condition.
  • The study 6 discusses the use of combined oral contraceptives, including cyproterone acetate/ethinyl estradiol, but it does not specifically address menstrual regulation.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Use of cyproterone acetate/ethinylestradiol in polycystic ovary syndrome: rationale and practical aspects.

The European journal of contraception & reproductive health care : the official journal of the European Society of Contraception, 2017

Research

The use of cyproterone acetate/ethinyl estradiol in hyperandrogenic skin symptoms - a review.

The European journal of contraception & reproductive health care : the official journal of the European Society of Contraception, 2017

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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