natural-estrogens.org
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The Value of Natural Estrogens in Combined Hormonal Contraception
Rethinking clinical practice, guidelines and global access
INTRODUCTION
Combined hormonal contraceptives (CHCs) have transformed reproductive health over the past decades, but the next era of innovation lies in the use of natural estrogens.
Evidence from pharmacodynamics, pharmacokinetics, clinical studies, and patient-reported outcomes suggests that natural estrogens offer benefits that more closely align with physiological needs, may reduce safety concerns associated with synthetic estrogens, and enhance overall acceptability. Despite these advantages, access remains uneven, and many countries still lack access to these options. It is time for a paradigm shift in how natural estrogens are integrated into guidelines, policies, and global health strategies.
A Global Initiative for Change
The Estrogens and Combined Oral Contraceptives Expert Committee (ESCONEC) Project brings together international experts to examine how the estrogen component shapes the acceptability, safety, and effectiveness of CHCs.
Its mission is to ensure that women everywhere can benefit from innovations that reflect both scientific evidence and individual priorities. The project advocates for a reevaluation of clinical practice, regulatory frameworks, and global health policies to ensure that contraceptive care becomes more equitable and evidence-based.
From Knowledge to Action
The project is built around a concise position statement outlining the rationale for change, along with 14 supporting sections. These sections delve into the pharmacological, clinical, societal, and environmental dimensions of estrogen choice in CHCs, while also citing all relevant sources and references. Together, they provide the foundation for a new global conversation, one that promotes innovation, equity, and sustainability in reproductive health.
Why natural estrogens?
The estrogen component defines much of the benefit–risk profile of CHCs. Natural estrogens, due to their metabolism and physiological effects, offer advantages that synthetic compounds cannot fully replicate.
Their metabolic pathways resemble those of endogenous hormones, reducing hepatic load and promoting a more favourable balance of coagulation, lipid, and bone health markers. They support bleeding control, resulting in more predictable cycle regulation and improved adherence and satisfaction. In addition, they contribute therapeutic value beyond contraception, with potential benefits for bone health, mood, and skin, supporting women throughout adolescence, the reproductive years, and the menopausal transition.
Safety and Tolerability Beyond Thrombosis
Safety has long been at the centre of debates around CHCs. Evidence suggests that natural estrogens do not increase, and may even reduce, thrombotic risk compared to synthetic estrogens.
Importantly, the safety discussion should not be limited to thrombosis alone. Broader aspects of safety, including metabolic, cardiovascular, and oncological outcomes, tend to be favourable or neutral with natural estrogens. Equally important is tolerability, which encompasses emotional and sexual well-being and reflects areas highly valued by women but often overlooked in regulatory considerations. Patient-reported outcomes provide an additional perspective, giving women’s priorities a voice and emphasising quality of life and cultural acceptance as valid endpoints for both clinicians and policymakers.
Access,
Culture, and Environment
Despite robust scientific evidence, natural estrogens remain unavailable in many countries. This leads to inequity in contraceptive choices, especially in regions where cultural or personal values heavily influence decisions.
Counselling and person-centred care must incorporate women’s priorities, including their concerns about safety, contraception, and overall well-being. Cultural diversity also plays a crucial role. Family planning strategies differ across regions and communities, requiring contraceptive options that are adapted to local needs. Environmental sustainability adds another layer to policy discussions, highlighting the ecological impact of hormonal options and the duty of regulators to consider environmental outcomes when determining access to contraception.
The need to reconsider guidelines and policies
Current contraceptive guidelines have not fully integrated the evidence supporting natural estrogens.
This lag has real consequences: clinicians lack the tools to counsel effectively, regulators delay access to safer and more acceptable options, and women are denied equitable choice. Guidelines must evolve to reflect the breadth of clinical evidence, patient-reported outcomes, and cultural realities. Regulatory frameworks should accelerate approvals, recognising natural estrogens as a genuine advance in safety and acceptability. Global health strategies must also ensure that access is not restricted to certain countries but becomes a standard of care worldwide.
A forward-looking call to action
The future of contraceptive care relies on innovation that is both evidence-based and person-centred.
Clinicians should champion access to natural estrogens and include them in counselling. Regulators and policymakers must act promptly to harmonise approvals and guidelines so women worldwide can access the same standard of care. Global health organisations, including FIGO and WHO, have a duty to incorporate natural estrogens into reproductive health frameworks and essential medicines lists. Industry and payers must also commit to ensuring equitable availability and affordability.
Conclusion
Natural estrogens represent the next frontier in combined hormonal contraception. Their clinical profile, safety record, and cultural and personal relevance create an opportunity to redefine standards in reproductive health. To ignore this evidence is to deny women better contraceptive care. To act is to embrace a new standard of innovation, equity, and sustainability.
Sections
Section 01
V1.0 10nov2025
Family planning, fertility care and contraceptive counselling
Gemzell-Danielsson K, Yadav A, Petta CA
Family planning, fertility care, and contraceptive care are interrelated yet distinct components of reproductive health, each reflecting evolving paradigms in health policy, human rights, and clinical practice. According to the World Health Organization (WHO), family planning refers to the ability of individuals and couples to anticipate and attain their desired number of children and determine the timing and spacing of pregnancies through the use of contraceptive methods and the treatment of…
Section 02
V1.0 10nov2025
Contraception: general considerations
Gemzell-Danielsson K, Sridhar A, Osuga Y, Barriga P
Contraception is a fundamental component of reproductive health, yet its use, acceptance, and outcomes vary significantly across global regions. These differences are shaped by a wide range of cultural, socioeconomic, and policy factors that influence both method preferences and access. From regional variations in contraceptive use to the impact of societal norms, healthcare infrastructure, and religious beliefs, understanding these dynamics is key to…
Section 03
V1.0 10nov2025
Mechanisms of action of estrogens and their physiological effects
Arnal JF, Taylor HS, Osuga Y, Foidart JM
Estrogens exert a wide range of biological effects through complex mechanisms of action that extend beyond reproductive regulation. Their influence spans the cardiovascular, skeletal, dermal, immune, and central nervous systems (Table 1), mediated by both genomic pathways (through direct or indirect modulation of gene transcription) and non-genomic pathways (through rapid, membrane-initiated signalling).
Section 04
V1.0 10nov2025
Absorption, distribution, metabolism, and excretion of estrogens used in combined oral contraceptives
Stanczyk FZ, Taylor H, Gaspard U
Understanding the pharmacokinetic and metabolic profiles of estrogens is essential for optimisingcontraceptive efficacy and safety. The pharmacokinetic behaviour of estrogens in combined hormonal contraceptives is determined by the interrelated processes of absorption, distribution, metabolism, and excretion (ADME). This section provides an overview of the ADME characteristics of the three main estrogens used in combined oral…
Section 05
V1.0 10nov2025
Clinical Applications of Estrogens in Adolescence and the Menopausal Transition
A Sridhar, K Gemzell Danielsson, U Gaspard, P Barriga, T de Villiers
Estrogen-containing contraceptives are vital for reproductive health across life stages, with natural, body-identical estrogens offering a safer and more metabolically favourable alternative to synthetic formulations, whose unique pharmacological properties ensure effective contraception and therapy with reduced health risks for adolescents, young, and midlife women [1-3]. In adolescents and young adults, COCs with natural estrogens (estradiol [E2] and estetrol [E4]) show benefits…
Section 06
V1.0 10nov2025
Bleeding outcomes and cycle control in combined hormonal contraception
Archer D, Mansour DJ, Creinin MD
Unpredictable bleeding is a common concern among users of hormonal contraception and a leading cause of early discontinuation. For combined hormonal contraception (CHC) users, the severity and pattern of bleeding changes depend on the type and dose of estrogen and progestogen, with bleeding often improving with duration of use. While the synthetic estrogen ethinylestradiol (EE) has long been the standard estrogen component, newer formulations…
Section 07
V1.0 10nov2025
Therapeutic benefits of the estrogen component in combined hormonal contraceptives
Piltonen T, Osuga Y, Bitzer J
While the negative effects of combined oral contraceptives (COCs) often receive considerable attention, their numerous positive effects are frequently underestimated and underreported. Estrogens play a crucial role in the non-contraceptive benefits of COCs, and selecting the appropriate oestrogen-progestin combination can help alleviate symptoms in various clinical scenarios.
Section 08
V1.0 10nov2025
Thrombosis
Douxfils J, Gaspard U, Creinin MD
Venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), is a major global public health issue that contributessignificantly to preventable morbidity and mortality, accounting for one in four deaths globally. Although most commonly associated with older populations, VTE also affects younger women, particularly due to iatrogenic factors such as the use of combined hormonal contraceptives (CHCs). Large observational studies estimate…
Section 09
V1.0 10nov2025
Safety of estrogens in combined hormonal contraceptives: evidence beyond thrombotic risk
Foidart JM, Piltonen T, Creinin MD
The estrogen and progestin components of combined hormonal contraceptives (CHCs)primarily function to prevent pregnancy by inhibiting ovulation and altering cervical mucus. Menstrual benefits are realised due to the manner in which the hormones limit endometrial development, resulting in reduced menstrual blood loss and alleviation of menstrual pain. CHCs also provide several additional non-contraceptive health benefits, including…
Section 10
V1.0 10nov2025
Tolerability of combined oral contraceptives - physical, emotional and sexual well-being perception
Piltonen T, Gemzell-Danielsson K, Sridhar A
The specific pairing of estrogens and progestins in a combined oral contraceptive (COC) meaningfully shapes tolerability. In practice, continuation depends less on efficacy than on lived experience, particularly in terms of bleeding patterns, mood stability, and sexual well-being. Most side effects are mild and often settle with continued use or a switch to an alternative formulation. Because tolerability reflects the combined action of both…
Section 11
V1.0 10nov2025
Patient-reported outcomes in contraceptive use
Bitzer J, Fruzzetti F, Yadav A
Contraceptive decision-making is a deeply personal and culturally mediated process shaped by the availability of methods, access to healthcare, and structural inequalitieson one hand, and individual preferences as well as social values on the other hand.
While efficacy, safety and availability are universal priorities, the values and expectations surrounding contraception vary significantly across countries and…
Section 12
V1.0 10nov2025
Access to contraception across the world
Petta CA, Obiol Saiz M, Fruzzetti F, Yadav A
Access to modern contraceptives varies widely across regions, shaped by socio-economic, cultural, and policy-related factors. While some countries have made significant progress, others continue to face substantial barriers, including financial constraints, restrictive laws, religious opposition, and social stigma. The scale of the issue is underscored by the fact that, in 2021, approximately 164 million women of reproductive age worldwide lacked access to the…
Section 13
V1.0 10nov2025
Social media and contraceptive decision-making across the life course
Obiol Saiz M, Sridhar A, Piltonen T, Yadav A, Díaz Yamal IJ
The rise of social media has changed how women at different life stages access, interpret, and act on information about contraception. Platforms like YouTube, TikTok, and Instagram have become key in shaping contraceptive choices, often highlighting personal experiences, cultural stories, and misinformation. This influence is powerfulwhere formal sexual education is limited or unavailable. For many, particularly adolescents and marginalised groups, these platforms act as…
Section 14
V1.0 10nov2025
Hormonal contraception and environmental impact
Piltonen T, Gemzell Danielsson K, Petta CA, Black DArnal JF, Taylor HS, Osuga Y, Foidart JM
Environmental pollution has a significant impact on women’s health throughout their lives.
These compounds enter surface water and treated drinking water, where they act as endocrine-disrupting compounds (EDCs), mimicking or blocking natural hormones and disrupting vital biological processes. Their persistence in aquatic environments not only endangers biodiversity but also poses health risks for…
Section 15
V1.0 10nov2025
Acknowledgements
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This project is supported by members of the EStrogens and combined oral CONtraceptives Expert Committee (ESONEC), a group of clinical experts and academic advisors from across Europe, Asia, and the Americas.
Section 01
V1.0 10nov2025
Family planning, fertility care and contraceptive counselling
Gemzell-Danielsson K, Yadav A, Petta CA
Section 02
V1.0 10nov2025
Contraception: general considerations
Gemzell-Danielsson K, Sridhar A, Osuga Y, Barriga P
Section 03
V1.0 10nov2025
Mechanisms of action of estrogens and their physiological effects
Arnal JF, Taylor HS, Osuga Y, Foidart JM
Section 04
V1.0 10nov2025
Absorption, distribution, metabolism, and excretion of estrogens used in combined oral contraceptives
Stanczyk FZ, Taylor H, Gaspard U
Section 05
V1.0 10nov2025
Clinical Applications of Estrogens in Adolescence and the Menopausal Transition
A Sridhar, K Gemzell Danielsson, U Gaspard, P Barriga, T de Villiers
Section 06
V1.0 10nov2025
Bleeding outcomes and cycle control in combined hormonal contraception
Archer D, Mansour DJ, Creinin MD
Section 07
V1.0 10nov2025
Therapeutic benefits of the estrogen component in combined hormonal contraceptives (beyond contraception)
Piltonen T, Osuga Y, Bitzer J
Section 08
V1.0 10nov2025
Thrombosis
Douxfils J, Gaspard U, Creinin MD
Section 09
V1.0 10nov2025
Safety of estrogens in combined hormonal contraceptives: evidence beyond thrombotic risk
Foidart JM, Piltonen T, Creinin MD
Section 10
V1.0 10nov2025
Tolerability of combined oral contraceptives - physical, emotional and sexual well-being perception
Piltonen T, Gemzell-Danielsson K, Sridhar A
Section 11
V1.0 10nov2025
Patient-reported outcomes in contraceptive use
Bitzer J, Fruzzetti F, Yadav A
Section 12
V1.0 10nov2025
Access to contraception across the world
Petta CA, Obiol Saiz M, Fruzzetti F, Yadav A
Section 13
V1.0 10nov2025
Social media and contraceptive decision-making across the life course
Obiol Saiz M, Sridhar A, Piltonen T, Yadav A, Díaz Yamal IJ
Section 14
V1.0 10nov2025
Hormonal contraception and environmental impact
Piltonen T, Gemzell Danielsson K, Petta CA, Black D
Section 15
V1.0 10nov2025
Acknowledgements
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