Oral Contraceptives: The Benefits, the 7 Potential Risks, and the Unasked Questions
Introduction
For over sixty years, oral contraceptives (OCPs) have been prescribed to hundreds of millions of women — celebrated as a liberation technology, a cultural inflection point, a way to reclaim autonomy over reproduction. But we rarely ask the more radical, more intimate question: What do they do to us?
The truth is less settled than you might assume. Oral contraceptives work. They reduce unintended pregnancies, manage acne, regulate bleeding, and mitigate conditions like endometriosis and depending on duration, ovarian cancer. However, beneath those clear benefits, the physiological trade-offs remain poorly understood, especially for women under 40 navigating the delicate hormonal choreography of energy, mood, metabolism, and longevity.
Most large-scale studies on OCPs are observational rather than mechanistic. We know they “work” at a population level, but we lack deep phenotyping of how they alter biology — and how those alterations interact with sleep, stress, gut health, and brain function. In this space of uncertainty, women deserve both clarity and agency.
The Benefits We Can Measure
OCPs remain one of the most effective tools for fertility control, but their therapeutic footprint extends further:
– Pregnancy prevention: Typical-use efficacy remains >91%, with perfect use approaching 99%.
– Cycle regulation: For women with irregular bleeding, OCPs can offer predictability and lighter periods.
– Symptom relief: OCPs are frontline treatments for endometriosis, premenstrual dysphoric disorder (PMDD), and heavy menstrual bleeding.
– Non-contraceptive perks: Reduced risks of ovarian and endometrial cancers emerge after five or more years of use.
But here’s where the narrative frays: prevention comes with biological trade-offs, trade-offs that have mostly been underexplored and underfunded.
The 7 Risks Beneath the Surface
1. Low-Grade Systemic Inflammation
Combined OCPs significantly raise oxidative stress and high-sensitivity C-reactive protein (hsCRP), a marker of low-grade inflammation and cardiometabolic risk. Up to 41% of users have hsCRP levels ≥2 mg/L versus just 8 to 10% of non-users. Overall, I see a doubling to tripling of this inflammatory marker in my medical practice.
2. The Androgen Gap: Low Testosterone, Vaginal Dryness, and Libido
Beyond the more visible metabolic effects, oral contraceptives also suppress free testosterone by elevating sex hormone–binding globulin (SHBG), leaving many women with androgen levels below their physiologic baseline. While the ovaries and adrenals continue to produce testosterone, much of it becomes biologically unavailable once SHBG rises two- to threefold. The evidence shows that free testosterone can drop by more than 60 percent. The clinical manifestations are often dismissed as “psychological” or “stress-related,” yet they are unmistakably embodied: diminished libido, vaginal dryness, less responsive arousal, and even subtle declines in sexual satisfaction. These are not rare side effects; they are the lived reality of many women on OCPs, mediated not by mood alone but by measurable shifts in hormonal bioavailability. The tragedy is not that these changes occur, but that women are rarely warned, rarely monitored, and rarely offered alternatives tailored to their biology.
3. Metabolic Shifts
Ethinyl estradiol, a common OCP component, drives adverse lipid changes: elevated triglycerides, total cholesterol, and LDL-C. These effects are modest but clinically relevant for women with pre-existing metabolic risk. Progestin-only pills fare better metabolically, but are less widely prescribed.
4. Crohn’s Disease and Microbiome Alterations
Consistent associations link OCPs to an increased risk of Crohn’s disease (OR ≈ 1.6), with longer use amplifying risk. Mechanistically, exogenous estrogen may alter gut permeability and the intestinal microbiome, shifting immune responses in ways we don’t yet fully understand.
5. Persistently Elevated SHBG
OCPs boost sex hormone-binding globulin (SHBG) levels by ~200%, lowering free testosterone and estradiol. While levels decline after discontinuation, they do not return to pre-treatment baseline in the studies one year after women stop. Persistently elevated SHBG during use affects energy, libido, and mood.
6. Neuroendocrine Effects
Oral contraceptives are associated with higher depressive and stress scores in some users, likely mediated through altered cortisol-binding proteins and reduced free sex steroids.
7. Blood Clot Risk
Combined OCPs increase venous thromboembolism risk approximately twofold compared to non-use, particularly with higher-dose ethinyl estradiol formulations.
What’s Missing From the Conversation
Much of the OCP data comes from large epidemiologic studies, designed to detect rare, catastrophic outcomes (e.g., blood clots, cancers). But we lack trials examining female-specific resilience markers:
– Sleep architecture: How OCP-driven hsCRP elevation alters deep sleep.
– HRV and cortisol rhythms: Do hormonal contraceptives blunt the HPA axis?
– Brain energetics: How synthetic hormones interact with mitochondrial efficiency in the female brain.
– Long-term metabolic programming: Do adolescent users have different aging trajectories?
We’ve treated OCPs like a solved question — they aren’t.
Reclaiming the Narrative
If the story of oral contraceptives began as liberation, the next chapter is about precision.
Women deserve:
– Better measurement: hsCRP, fasting insulin, ferritin, SHBG, microbiome panels.
– Better personalization: Matching formulations to individual metabolic, inflammatory, and neurocognitive profiles.
– Better alternatives: Non-hormonal tools and low-dose regimens backed by modern trials.
The next frontier of women’s health isn’t about taking choices away; it’s about giving women more informed choices.
Conclusion
OCPs remain powerful tools — but they aren’t neutral. For millions of women, they represent freedom, control, and relief. But they also quietly rewrite the scripts of inflammation, metabolism, and mood, in ways science is only beginning to decode.
The choice to use them should be deeply personal, but it should also be deeply informed. Women deserve both the data and the dignity to decide. Let’s keep pushing for more answers and better women’s health research in areas like oral contraceptive risks, benefits, and alternatives.
Endnotes
Brabaharan, S., et al. “Association of Hormonal Contraceptive Use with Adverse Health Outcomes: An Umbrella Review.” JAMA Network Open 5, no. 1 (2022): e2143730. https://doi.org/10.1001/jamanetworkopen.2021.43730.
Cauci, S., Xet al. “Oxidative Stress Is Increased in Combined Oral Contraceptives Users and Is Positively Associated with High-Sensitivity C-Reactive Protein.” Molecules, 26(4), 1070, 2021. https://doi.org/10.3390/molecules26041070.
Masama, C., et al. “Hormone Contraceptive Use in Young Women: Altered Mood States, Neuroendocrine and Inflammatory Biomarkers.” Hormones and Behavior 144 (2022): 105229. https://doi.org/10.1016/j.yhbeh.2022.105229.
Panzer, C., et al. “Impact of Oral Contraceptives on Sex Hormone-Binding Globulin and Androgen Levels: A Retrospective Study in Women with Sexual Dysfunction.” Journal of Sexual Medicine 3, no. 1 (January 2006): 104–13. https://doi.org/10.1111/j.1743-6109.2005.00198.x.
Pasvol, T.J., et al. “Use of Contraceptives and Risk of Inflammatory Bowel Disease: A Nested Case-Control Study.” Alimentary Pharmacology & Therapeutics 55, no. 3 (2022): 318–26. https://doi.org/10.1111/apt.16647.
Toffol, E., et al. “Cross-Sectional and Longitudinal Metabolomics-Based Profiles Associated with Oral Contraceptive and Progestin-Only Pill Use: A Finnish Population-Based Study.” Acta Obstetricia et Gynecologica Scandinavica, 2025. https://doi.org/10.1111/aogs.15176.
Turki, A., et al. “Effects of Hormonal Contraceptives on Lipid Profile Among Women Attending Family Planning Unit in Goba Town Public Health Facilities, Bale, Southeast Ethiopia: A Comparative Cross-Sectional Study.” Reproductive Health 20, no. 1 (2023): 185. https://doi.org/10.1186/s12978-023-01727-4.
Wang, Q., et al. “Effects of Hormonal Contraception on Systemic Metabolism: Cross-Sectional and Longitudinal Evidence.” International Journal of Epidemiology 45, no. 5 (2016): 1445–57. https://doi.org/10.1093/ije/dyw147.
Zimmerman, Y., et al. “The Effect of Combined Oral Contraception on Testosterone Levels in Healthy Women: A Systematic Review and Meta-Analysis.” Human Reproduction Update 20, no. 1 (2014): 76–105. https://doi.org/10.1093/humupd/dmt038.