The shorter, the better: A review of the evidence for a shorter contraceptive hormone-free interval

Abstract

Objectives The menstrual cycle is characterised by cyclical fluctuations in oestrogens, progesterone and androgens. Changes in hormone levels in the premenstrual phase with the decline in progesterone trigger a physiological reaction which culminates in menstruation. This process is accompanied in many women by various symptoms such as pelvic pain, headache, mood disorders and gastrointestinal discomfort. The aim of this article was to summarise the latest findings on the physiology and pathophysiology of menstruation and review the impact of shortening the hormone-free interval (HFI) on the health and wellbeing of women.

Results Menstruation can be viewed as an inflammatory event in which local and systemic effects produce symptoms in genital and extragenital regions of the body. The mast cells are the main mediator of this reaction. In women using hormonal contraceptives, menstrual bleeding is not biologically necessary and it may be advantageous to maintain more stable levels of oestrogens, progesterone and androgens throughout the cycle. New combined oral contraceptives (COCs) have been formulated with a progressively shorter HFI (24/4 and 26/2) than traditional 21/7 pills, with the rationale of reducing hormone withdrawal- associated symptoms. Several studies have shown the beneficial effects of these regimens, which reduce the inflammatory exposure of the female organism and thus have the capacity to increase the quality of life of women. A combination of estradiol valerate (E₂V) and dienogest (DNG) is administered on the shortest 26/2 regimen. This regimen has a broad evidence base from randomised controlled trials that have examined the impact of E₂V/DNG on symptoms and quality of life.

Conclusions Shortening the HFI reduces the occurrence of bleeding-related inflammatory processes and subsequent physical and mental symptoms. The shortest interval with evidence of reproductive and sexual health benefits is provided by a 26/2 regimen.

KEYWORDS:

• Dienogest
• Dysmenorrhoea
• Estradiol valerate
• Female sexual dysfunction
• Hormone-free interval
• Inflammation
• Menstrual symptoms
• Oral contraception

ACKNOWLEDGEMENTS

The content of the paper was entirely selected, structured and drafted by Professor Graziottin, who has presented it at many global, international and national meetings. She was later assisted in the final preparation of the text by professional medical writers at Sudler and Hennessey SRL (Milan, Italy). The medical writing support was funded by Bayer HealthCare Pharmaceuticals (Berlin, Germany).

Declaration of interest: Professor Graziottin is currently a member of the speakers’ bureaux for Abbott, Bayer HealthCare, Deakos, LoliPharm, Menarini and Shionogi. In 2014–2015 she participated on scientific advisory boards for Bayer HealthCare, Fidia and Menarini and worked as a consultant for Bayer HealthCare, Deakos, Epitech, Fidia, Lolipharm and Menarini.