COC with natural estrogen (quadriphasic)
Updated · Methodology
First line
Regular contraception, especially in women >35 and with sensitivity to ethinylestradiol. Per SEGO 2023, Qlaira is recommended for heavy and prolonged menstrual bleeding – -approved for this (PRO-MENS RCT 2014). 26 active + 2 placebo tablets.
Sources
ICD-10: Z30.0 · ICD-11: QA21
First line
Heavy menstrual bleeding in women without organic pathology (fibroids, adenomyosis, polyps). PRO-MENS RCT 2014 showed 88% reduction in menstrual blood loss vs placebo. Per NG88 2018 and SEGO 2023, drug of choice in women who also need contraception. Alternative – LNG-IUS (Mirena) with up to 90% blood loss reduction.
Sources
ICD-10: N92.0 · ICD-11: GA20.50
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
Qlaira during breastfeeding. MEC 2015 category 4 first 6 weeks, then 2. Although estradiol is natural (milder than ethinylestradiol), it still reduces milk supply. Dienogest transfers to milk in small amounts (RID about 1%). Progestin-only is preferred.
Sources
ICD-10: Z30.0 · ICD-11: QA21
Estradiol valerate hydrolyzes to estradiol – a natural estrogen identical to endogenous. Dienogest is an antiandrogenic progestin. The quadriphasic Qlaira regimen mimics the natural cycle with decreasing estrogen and increasing progestin doses. Hemostasis effects are milder than with ethinylestradiol – VTE risk is intermediate (INAS-FOCUS study).
Discontinue if pregnant.
Estradiol reduces milk supply, milder than ethinylestradiol. WHO MEC first 6 weeks – category 4. Dienogest RID about 1%, Hale L3.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
Verbatim lines from the interaction sections, in the language of the label
«Effects of Combined Oral Contraceptives on Other Drugs: COCs containing ethinyl estradiol may inhibit the metabolism of other compounds. COCs have been shown to significantly decrease plasma…»FDA, section 7 · Open on DailyMed
«Effects of Other Drugs on Combined Oral Contraceptives: Substances Increasing the Systemic Exposure of COCs (enzyme inhibitors): Concomitant administration of moderate or strong CYP3A4 inhibitors…»FDA, section 7 · Open on DailyMed
«Effects of Other Drugs on Combined Oral Contraceptives: Drugs or herbal products that induce certain enzymes, including CYP3A4, may decrease the effectiveness of COCs or increase breakthrough…»FDA, section 7 · Open on DailyMed
«Effects of Other Drugs on Combined Oral Contraceptives: Drugs or herbal products that induce certain enzymes, including CYP3A4, may decrease the effectiveness of COCs or increase breakthrough…»FDA, section 7 · Open on DailyMed
«Effects of Other Drugs on Combined Oral Contraceptives: Substances Increasing the Systemic Exposure of COCs (enzyme inhibitors): Concomitant administration of moderate or strong CYP3A4 inhibitors…»FDA, section 7 · Open on DailyMed
«Effects of Other Drugs on Combined Oral Contraceptives: Substances diminishing the efficacy of COCs: Dienogest is a substrate of CYP3A4. Women who take medications that are strong CYP3A4 inducers…»FDA, section 7 · Open on DailyMed
«Effects of Other Drugs on Combined Oral Contraceptives: Substances Increasing the Systemic Exposure of COCs (enzyme inhibitors): Concomitant administration of moderate or strong CYP3A4 inhibitors…»FDA, section 7 · Open on DailyMed
«Effects of Other Drugs on Combined Oral Contraceptives: Substances Increasing the Systemic Exposure of COCs (enzyme inhibitors): Concomitant administration of moderate or strong CYP3A4 inhibitors…»FDA, section 7 · Open on DailyMed
«Effects of Other Drugs on Combined Oral Contraceptives: Substances Increasing the Systemic Exposure of COCs (enzyme inhibitors): Concomitant administration of moderate or strong CYP3A4 inhibitors…»FDA, section 7 · Open on DailyMed
«Effects of Other Drugs on Combined Oral Contraceptives: Substances Increasing the Systemic Exposure of COCs (enzyme inhibitors): Concomitant administration of moderate or strong CYP3A4 inhibitors…»FDA, section 7 · Open on DailyMed
«Effects of Other Drugs on Combined Oral Contraceptives: Substances Increasing the Systemic Exposure of COCs (enzyme inhibitors): Concomitant administration of moderate or strong CYP3A4 inhibitors…»FDA, section 7 · Open on DailyMed
«Effects of Other Drugs on Combined Oral Contraceptives: Substances Increasing the Systemic Exposure of COCs (enzyme inhibitors): Concomitant administration of moderate or strong CYP3A4 inhibitors…»FDA, section 7 · Open on DailyMed
«Effects of Other Drugs on Combined Oral Contraceptives: Substances Increasing the Systemic Exposure of COCs (enzyme inhibitors): Concomitant administration of moderate or strong CYP3A4 inhibitors…»FDA, section 7 · Open on DailyMed
«Effects of Other Drugs on Combined Oral Contraceptives: Drugs or herbal products that induce certain enzymes, including CYP3A4, may decrease the effectiveness of COCs or increase breakthrough…»FDA, section 7 · Open on DailyMed
«Effects of Other Drugs on Combined Oral Contraceptives: Drugs or herbal products that induce certain enzymes, including CYP3A4, may decrease the effectiveness of COCs or increase breakthrough…»FDA, section 7 · Open on DailyMed
«Effects of Other Drugs on Combined Oral Contraceptives: Substances Increasing the Systemic Exposure of COCs (enzyme inhibitors): Concomitant administration of moderate or strong CYP3A4 inhibitors…»FDA, section 7 · Open on DailyMed
«Effects of Other Drugs on Combined Oral Contraceptives: Substances Increasing the Systemic Exposure of COCs (enzyme inhibitors): Concomitant administration of moderate or strong CYP3A4 inhibitors…»FDA, section 7 · Open on DailyMed
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Estradiol valerate + Dienogest is evaluated for the following indications with varying evidence strength: Contraception (evidence tier A), Heavy menstrual bleeding (evidence tier A), Contraception during breastfeeding (evidence tier D). See the full indication matrix with dosing and citations above on this page.
Common side effects of Estradiol valerate + Dienogest (≥ 1 in 100): Headache, Breast tenderness, Nausea, Acne (rare with dienogest), Amenorrhea (3–12%). See the Safety section for uncommon and serious reactions.
Discontinue if pregnant.
Estradiol reduces milk supply, milder than ethinylestradiol. WHO MEC first 6 weeks – category 4. Dienogest RID about 1%, Hale L3.
Estradiol valerate + Dienogest is contraindicated in: VTE; Thrombophilia; Smoking after 35; Migraine with aura; HTN. Full list in the Safety section.
Direct links to regulator labels. Open in a new tab.
Ethinylestradiol, Ethinylestradiol + Desogestrel, Ethinylestradiol + Gestodene, Ethinylestradiol + Levonorgestrel, Ethinylestradiol + Norgestimate, Mifepristone, Tibolone, Desogestrel