Steroid hormones — including glucocorticoids (like cortisol) and sex steroids (estrogens, androgens) — are central regulators of metabolism, immunity, bone health and red blood cell production. Clinicians rely on hormone measurements for diagnosis and treatment of endocrine disorders, and epidemiologists study hormone patterns to understand disease risk across populations.
Yet despite their importance, we have had an incomplete picture of how steroid hormone levels vary in healthy adults according to age, sex and common lifestyle factors. A new large-scale analysis published in Science Advances provides one of the clearest snapshots to date of how sex, aging, genetics and day-to-day behaviors such as use of oral contraceptives and smoking shape circulating steroid hormone profiles in healthy people aged 20–79 years.
The study—reported by Léa Deltourbe et al. and led by scientists from the 米利厄·伊内里奥联盟—measured steroids in nearly 1,000 healthy adults and re-measured many donors after a decade. Its findings have practical implications for clinicians, researchers and anyone who uses or prescribes steroid-influencing medications.
What the Data Tell Us
The study analyzed a comprehensive panel of circulating steroid hormones in a large, diverse group of healthy adults. Rather than focusing on single hormones, the investigators examined patterns across multiple steroids simultaneously and looked for associations with biological sex, age, genetic factors and lifestyle measures.
Major patterns reported by the authors include:
– Sex- and age-dependent hormone trajectories: As expected, men and women had distinct steroid profiles. The team also observed age-related declines in specific androgens in men over the 10-year follow-up, a change that correlated with increased risk for several age-related conditions.
– Strong effects of oral contraceptives in women: In women of reproductive age, use of combined oral contraceptives (COCs) was associated with altered levels of many steroids. The study found that 12 measured steroids differed between women taking oral contraceptives and women not taking them. Notably, cortisol and cortisone — glucocorticoids involved in the stress response — were higher among women on COCs.
– Smoking shapes male steroid profiles and affects female estrogens: In men, smoking was associated with widespread changes across nearly all steroid measures. One highlighted observation was higher levels of androstenedione in current-smoking men compared with non-smokers or former smokers. In women, smoking was linked to lower estradiol (E2) levels in some analyses.
– Lifestyle, plasma proteins and genetics matter: Beyond contraceptives and smoking, the authors report that plasma protein concentrations, genetic background and other lifestyle variables (for example, diet and activity, captured to varying extents) influence steroid distributions.
Why these findings matter clinically: Steroid hormones are not static background variables. Broad shifts—driven by medications or behaviors—can alter disease risk, affect immune responses and complicate interpretation of hormone tests. For instance, higher circulating cortisol is linked with obesity, mood disorders and cardiovascular risk in multiple other studies; if oral contraceptives elevate glucocorticoid measures, clinicians should recognize this when interpreting single-point cortisol tests.
Oral Contraceptives: Benefits and Broad Hormonal Effects
Combined oral contraceptives are used worldwide for pregnancy prevention, menstrual regulation and other indications. They generally contain an estrogen (often ethinylestradiol) plus a progestin and are known to affect the endocrine milieu. The new study reinforces that COCs do more than suppress ovulation: they can shift a broad array of circulating steroids.
Key points for clinicians and patients:
– Multisystem effects: The observed increases in cortisol and cortisone among COC users may influence physiologic stress responses measured in blood. Current evidence does not imply immediate harm for most users, but the long-term implications of small, persistent shifts in multiple steroid hormones remain under study.
– Disease associations are complex: Epidemiological data show that COC use reduces ovarian cancer risk — a protective effect consistent with reduced ovulatory frequency and hormonal modulation. At the same time, other risks and benefits (e.g., thrombotic risk with certain formulations) depend on dose, progestin type, age and smoking status.
– Practical takeaway: When evaluating hormone levels or new symptoms in women taking oral contraceptives, clinicians should consider the medication as a potential driver of hormone test abnormalities. Switching formulations or contraceptive methods is a reasonable clinical strategy in select situations, but the decision should balance contraceptive efficacy, side effects and individual risk factors.
Smoking: A Potent Modifier of Male and Female Steroid Landscapes
Cigarette smoking remains a leading modifiable cause of disease worldwide. Beyond its well-known risks to the lungs and cardiovascular system, smoking appears to meaningfully alter steroid hormone profiles.
Findings and implications:
– In men, smoking was associated with broad alterations in steroid levels, including higher androstenedione. Because androgens influence muscle, bone and metabolic function, smoking-driven hormonal shifts could contribute to the systemic health effects seen in smokers.
– In women, lower estradiol associated with smoking may have reproductive and bone-health implications.
– Immunologic intersection: The study also links smoking to changes in the immune system—short-term effects on innate immunity and longer-term impacts on adaptive immunity. Steroid hormones are immunomodulators, so some immune effects of smoking may be mediated through hormone changes.
Clinical implication: Smoking status is a relevant piece of information when interpreting steroid hormone tests or planning hormone-based therapies. Smoking cessation should be framed not only as cardiovascular and cancer prevention, but as a way to normalize endocrine and immune homeostasis.
Misconceptions and Harmful Behaviors
Common misunderstandings that this study helps correct:
– “Oral contraceptives only affect fertility-related hormones.” False — COCs influence a broader steroid network including glucocorticoids.
– “Hormone tests give a fixed picture regardless of behavior.” False — lifestyle, medications and smoking can shift steroid levels and change how results should be interpreted.
– “If a test is slightly abnormal, it must reflect disease.” Not necessarily—medication effects and transient lifestyle influences can produce measurable changes without underlying pathology.
Harmful behaviors amplified by misplaced assumptions:
– Self-modifying medication without guidance: Stopping contraception suddenly to ‘correct’ hormone labs may place a person at risk of unintended pregnancy or menstrual disruption.
– Ignoring smoking as an endocrine disruptor: Clinicians focused narrowly on metabolic or cardiac risk may miss smoking-related endocrine effects relevant to bone health, fertility or dosing of hormone therapies.
Correct Health Practices and Practical Advice
For clinicians:
– Document medication and smoking status before ordering steroid panels. Include oral contraceptive type (combined vs progestin-only), dose and duration.
– Interpret cortisol and sex-steroid levels in the context of COC use and smoking. If results are borderline or unexpected, consider repeating tests off hormonal contraception (when safe and acceptable) or after a period of smoking cessation.
– When initiating hormone therapy, counsel about behavioral factors (smoking cessation, weight management, diet and exercise) that influence both hormones and treatment response.
For patients:
– If you take oral contraceptives: discuss potential systemic hormone effects with your clinician, especially if you experience new symptoms (unexplained weight gain, mood changes, unusual fatigue).
– If you smoke: quitting benefits far more than your lungs. It can help normalize hormone patterns, improve immune function and reduce risks for many chronic diseases.
– Don’t stop or change prescription medications without medical advice.
Expert Insights
The study by Léa Deltourbe et al. adds momentum to an emerging view: hormone measurements are dynamic signals shaped by sex, age, genetics and the choices people make every day. Rather than single-number thresholds, clinicians should treat steroid profiles as context-dependent and integrate lifestyle information into diagnostic pathways.
Looking forward, the authors suggest additional work to clarify causal pathways (for example, whether contraceptive-driven glucocorticoid changes directly alter long-term disease risk) and to develop reference ranges that account for common exposures.
Patient Scenario: What to Tell Patients
Emily, 32, comes to clinic with concerns about recent weight gain and mood swings. She has been taking a combined oral contraceptive for five years. Her primary-care doctor orders a basic endocrine panel and notes slightly elevated cortisol and altered steroid ratios. Rather than alarming Emily, the doctor explains that oral contraceptives commonly change multiple steroid measures and that these lab differences do not by themselves indicate Cushing syndrome. Together they review her symptoms, consider non-hormonal contributors (sleep, diet, stress), and discuss contraceptive alternatives. If Emily is concerned, they plan a follow-up that might include repeating hormone testing after an informed contraceptive switch or additional clinical evaluation for mood and metabolic factors.
Key counseling points in this scenario:
– Explain medication effects on tests plainly and nonjudgmentally.
– Prioritize shared decision-making when considering changes in contraception.
– Address modifiable lifestyle factors (sleep, stress, smoking) that interact with hormones.
Conclusion
The large-scale study in Science Advances (Léa Deltourbe et al., 2025) deepens our understanding of steroid hormone variability in healthy adults. It shows that oral contraceptives and smoking are major, clinically relevant modifiers of the steroid milieu — effects that matter for disease risk assessment, interpretation of lab tests and therapeutic decisions. Clinicians should systematically record medication and smoking histories, and researchers should pursue causal studies and exposure-aware reference ranges. For patients, the practical messages are straightforward: don’t change medications without consulting your clinician, and recognize that quitting smoking has endocrine as well as cardiovascular and oncologic benefits.
References
Léa Deltourbe et al, Steroid hormone levels vary with sex, aging, lifestyle, and genetics, Science Advances (2025).
