There are many reasons that someone might opt to use oral contraceptives (OC) – including essential benefits like family planning, and relief from menstrual-related symptoms. OCs might also extend protective benefits for certain types of cancers and provide specific symptom relief for conditions like endometriosis and polycystic ovarian syndrome (PCOS).

However, they can also come with adverse side effects, including an increased risk of cardiovascular events, cerebral hemorrhage, gallbladder disease, and hepatic complications. Some more common side effects associated with OC use include depression, migraines, edema, allergic skin reactions, abdominal cramps, bloating, and carbohydrate intolerance, to name a few.

Contributing (at least in some part) to these risks are the potential depletions of essential nutrients and alterations to the gut microbiome that occur with OC use. In this article, we’ll examine the latest evidence on drug-induced nutrient depletions (DIND) related to OCs, the effects of OC use on the gut microbiome and microbiota metabolites, and conclude with general diet, lifestyle, and nutraceutical options to consider for birth control users. The goal is to find a balanced approach that respects an individual’s autonomy over their body, maximizes available medical choices, and minimizes any associated risk.

 

A Background on Oral Contraceptives

In the US, OC can be categorized into three types:

  • Combined estrogen-progesterone
  • Progesterone-only
  • Continuous or extended use

Examples of common OC Brands (not an exhaustive list; US brands)

OC Type Brand Name Ingredients
Combined estrogen-progesterone

● Includes mono- bi- ti- and quadrophasic formulations

● Differences include doses of both components and progesterone type

● Some formulations include nutrients like folate and iron for improved nutrient repletion

 Brevicon, Modicon, Wera, Balziva, Briellyn, Gildagia, Philith, Zenchent

Aranelle, Tri-Norinyl, Leena, Alyacen 7/7/7, Necon 7/7/7, Nortrel 7/7/7, Dasetta 7/7/7, Cyclafem 7/7/7

Loestrin, Microgestin, Tilia Fe

 Ethinyl Estradiol, Norethindrone
Estarylla, Previfem, Sprintec Ethinyl estradiol and norgestimate
Apri, Desogen, Juleber, Reclipsen, Kariva, Cyclessa, Solia, Mircette, Desogestrel, Ethinyl Estradiol
Safyral, Beyaz Drospirenone, ethinylestradiol, and levomefolate
Ocella, Yasmin, Zarah, Yaz Drospirenone and ethinylestradiol
Levora, Altavera, Lessina, Lybrel, Amethia Ethinyl Estradiol, Levonorgestrel
Continuous or extended use Amethia Lo, Camrese Lo, Daysee, Introvale, LoSeasonique, Jolessa Ethinyl Estradiol, Levonorgestrel
 Progestin-only Aygestin, Camila, Errin, Jolivette, Lyza, Nora-Be, Nor-QD, Ortho Micronor Norethindrone

 

How do Oral Contraceptives Work?

Oral contraceptives (OCs) contain synthetic hormones that mimic the natural hormones in the body. The two main types of hormones in these pills are estrogens and progestins.

Estrogens:

  • Regulate the menstrual cycle: Estrogens help maintain stable hormone levels and regulate the menstrual cycle.
  • Prevent ovulation: They prevent the ovaries from releasing an egg, a process known as ovulation.
  • Stabilize the uterine lining: Estrogens also stabilize the lining of the uterus, reducing the chances of irregular bleeding.

Progestins:

  • Prevent ovulation: Progestins play a crucial role in preventing ovulation.
  • Thicken cervical mucus: They thicken the mucus around the cervix, making it harder for sperm to enter the uterus and reach an egg.
  • Thin the uterine lining: Progestins thin the lining of the uterus, making it less likely for a fertilized egg to attach and grow.

While there are progestin-only formulations, combined estrogen-progestin pills are often more effective in preventing pregnancy by stopping ovulation, thickening cervical mucus, and thinning the uterine lining. However, progestin-only pills might be recommended in certain situations.

When Progestin-Only Pills Are Recommended:

  • Breastfeeding: Progestin-only pills are often recommended for individuals who are breastfeeding, as estrogens can reduce milk production.
  • Estrogen Sensitivity: For those who cannot tolerate estrogen due to side effects or health risks, progestin-only pills are a good alternative.
  • Medical Conditions: People with certain medical conditions, such as a history of blood clots, high blood pressure, or cardiovascular disease, may be advised to avoid estrogen-containing pills.
  • Migraines with Aura: Those who suffer from migraines with aura are generally advised to avoid estrogen-containing contraceptives due to an increased risk of stroke.
  • Older Age and Smoking: Individuals over 35 who smoke are at an increased risk of cardiovascular problems when using estrogen-containing contraceptives. Progestin-only pills are often a safer alternative.
  • Perimenopause: People going through perimenopause may use progestin-only pills to manage symptoms like irregular periods and to provide contraception during this transitional phase.

Progestin-only pills are highly effective when taken consistently at the same time every day, but they require strict adherence to the dosing schedule to maintain their effectiveness.

 

Therapeutic Uses of Oral Contraceptives

An estimated 25% of people (15 to 44 years-old) currently using contraception use OC as their method of choice. The most frequently prescribed OC is combined contraceptive; progesterone is the hormonal component that prevents pregnancy while the estrogen component controls menstrual bleeding.

Although most people take OCs to prevent pregnancy, approximately 14% are using them for non-contraceptive reasons. People with periods use OCs for menstrual-related disorders such as well as conditions like PCOS, acne, and osteopenia, and vasomotor symptoms associated with menopause.

 

Personalizing the OCs based on Components

In the combination pills, the estrogen component (i.e. usually Ethinyl Estradiol) is combined with various generations of progestin components (i.e. Norethindrone, Levonorgestrel, Drospirenone, Desogestrel, Norgestimate, or Norethindrone) with varying degrees of androgenic and progestogenic potential. In the US the most frequently prescribed formulations have drospirenone or norethindrone components.

These components have slightly different activity which might be favorable to different treatment goals, for example:

  • Some components of oral contraceptives (OC) can help manage symptoms such as heavy bleeding, pain, and androgenic symptoms like hirsutism and acne. These benefits are especially relevant for conditions like polycystic ovary syndrome (PCOS) and endometriosis. Endometriosis occurs when tissue similar to the uterine lining grows outside the uterus, causing pain and potentially leading to fertility issues.
  • Drospirenone suppresses ovulation and also has anti-mineralocorticoid activity which reduces fluid retention, edema and has some antiandrogenic activity making it useful in androgen-dominant conditions like PCOS.
  • Norethindrone primarily acts by thickening cervical mucus which reduces risk of pregnancy through multiple mechanisms as well as alters the endometrium. This can help in reducing pain and heavy periods, as well as other symptoms associated with endometriosis.

Contraceptive pills can be delivered as monophasic (same dose of both components in the active pills) or multiphasic (biphasic, triphasic, or quadrophasic). The latter contains varying weekly doses of either one or both components. This helps in personalization because it can better complement the natural cycle changes to reduce side effects and improve efficacy.

The formulation can also be personalized based on length and frequency of desired withdrawal bleeding, cyclic monthly bleeding (for example 7 days or 3 days), extended cyclic (every three months), or continuous (no bleeding).

Estrogen & Progestin Components commonly used in OC in the US

Estrogen component Estradiol, Ethinylestradiol, or Estetrol
First-generation progestin Norethindrone acetate, Ethynodiol diacetate, Lynestrenol, Norethynodrel
Second generation progestin Levonorgestrel,dl-Norgestrel
Third generation progestin Norgestimate, Gestodene, Desogestrel
Unclassified progestin Drospirenone, Cyproterone acetate

 

The Benefits of Oral Contraceptives

The United Nations (UN) and the World Health Organization (WHO) consider contraceptive access to be a human right and a public health priority. That’s partly because historically, access to contraception has afforded individuals better health, education, and financial outcomes.

Beyond contraception, oral contraceptives are also used to manage menstrual-related symptoms. These conditions can often leave those afflicted with pain, migraines, fatigue, dizziness, and other life-disrupting symptoms. Without these medications, it’s not an exaggeration to say that these individuals would be significantly disabled or unable to perform to their full potential in school or work.

In people experiencing menopausal symptoms (before the age of 60), OC can help reduce vasomotor symptoms as well as preserve bone density and prevent osteopenia and osteoporosis.

OCs are also known to reduce the risk of conditions like endometriosis and endometrial cancers. Epidemiologic evidence reports a 50% risk reduction of endometrial cancer among people who use combined OCs compared with those who have not, with the protective effect lasting up to 20 years. Furthermore, combined OC reduces risk of ovarian cancer by 27% and of colon cancer by 18%.

 

The Downside: Nutrient Depletion and Microbiome Disruptions

Despite the benefits, oral contraceptive use has also been associated with drug-induced nutrient depletions (DIND) of several micronutrients and disruptions in the gut microbiome. We’ll focus on the evidence available on these aspects and the subsequent impact on a woman’s health as a result of oral contraceptive use.

 

Nutrient Depletion: A Closer Look

Vitamins and minerals play crucial roles in our bodies. They are involved in numerous biological processes, including energy production, immune function, blood clotting, and maintaining the health of our skin, hair, and nails. Without these tiny powerhouses, our bodies wouldn’t be able to function at their best.

Oral contraceptives have been linked to lower levels of several vitamins and minerals, including vitamins B, C, and E, zinc, magnesium, and selenium. Mechanisms of these depletions vary, but largely involve altered absorption and metabolism.

Oral Contraceptives and Vitamin B Depletion

Oral contraceptives can reduce levels of several B vitamins, including B6, B5, B9 (folate), and B12. These vitamins are important for energy production, DNA synthesis, and brain health. However, the current literature isn’t clear about the need for supplementing these B vitamins, except for folate.

Folate is crucial for early embryo development, so it’s especially important for individuals  of childbearing age to continue folate supplementation while using oral contraceptives. Although reductions in B12 levels and increases in homocysteine and methylmalonic acid (MMA) are sometimes seen with oral contraceptive use, they are not usually significant or consistent enough to need special supplements. However, regular monitoring for signs of B12 deficiency can be helpful.

Oral Contraceptives and Mineral Depletion

Oral contraceptives can lead to a decrease in several essential minerals, including calcium, copper, iron, zinc, magnesium, and selenium. These minerals are vital for many body functions, such as immune function, skin and gut health, bone density, neurotransmitter production, glutathione production, hormone balance, and insulin and thyroid activity.

It’s particularly important to monitor iron levels, especially in people of childbearing age who are prone to iron deficiency anemia (IDA). This is particularly relevant for those who experience heavy menstrual bleeding, as they are at a higher risk for developing IDA. Regular monitoring and appropriate supplementation can help maintain healthy iron levels and overall well-being.

 

The Gut Microbiome and Oral Contraceptives

The gut microbiome is a complex community of microorganisms living in our intestines that plays a crucial role in our health. It helps digest food, regulates the immune system, protects against disease-causing pathogens, and produces small amounts of vitamins like B12 and K.

The gut also influences hormone regulation, particularly through the estrobolome, which is the group of gut bacteria involved in estrogen metabolism. Certain gut microbes produce beta-glucuronidase, an enzyme crucial for estrogen detoxification. An imbalance in the gut microbiome, known as dysbiosis, can disrupt this process and affect estrogen levels, potentially leading to health issues like obesity, metabolic syndrome, cancer, and cardiovascular disease. Some of these conditions overlap with the side effects of oral contraceptives (OCs).

External sources of estrogen, known as xenoestrogens (found in plastics, pesticides, etc.), can alter the gut microbiome. There’s a question about whether the estrogen in OCs contributes to this alteration. While hormone replacement therapy (HRT) is known to disrupt the gut microbiome, research has not clearly established that OCs cause dysbiosis. Studies show that OCs do not significantly affect gut microbiome diversity but may influence certain bacterial functions.

OCs are associated with higher levels of estradiol and sex hormone-binding globulin (SHBG), a protein that binds to sex hormones and regulates their activity. This may affect specific bacteria, such as Eubacterium ramulus.

 

Supporting Reproductive Health: A Balanced Approach

While the side effects, DIND, and GI-implications of OCs need to be considered, it’s essential that we balance them against the potential benefits. By supporting individuals in their decision to use OCs, we can improve their health and economic outcomes, build trust, and ensure they can maintain their bodily autonomy.

To comprehensively support patients taking oral contraceptives, we can apply a comprehensive functional medicine (FxMed) and personalized nutrition approach. Clinicians focusing on this whole-person approach can recommend:

  • A foundational antiinflammatory diet that includes macro- and micronutrient balance and diversity of antioxidants, fibers, and polyphenols to support gut health and integrity.
  • Basic supplementation strategy that covers the foundations of key minerals depleted, especially noting folate, zinc, selenium, and magnesium due to their implications in related conditions and health risks including skin health, gut support, and cardiometabolic risks.
  • Targeted GI and microbiome support is likely a useful strategy especially in people who are experiencing digestive and gut-related symptoms. Supporting healthy digestion, regular bowel movements, and addressing any gut-related problems should be part of the holistic strategy.
  • Consider regular monitoring of nutritional status and metabolic markers to personalize the strategy and catch any problems in advance. This is especially true for folate, B12, iron, magnesium, selenium, and zinc.

Other lifestyle strategies that support hormonal balance, neurotransmitter function, gut motility and hepatic function including stress management, movement, and sleep, and circadian rhythm syncing, are proving to have wide benefits and are a wise part of a truly holistic strategy.  And, as always, it’s essential for patients to discuss any concerns or side effects with their healthcare provider.

 

Nutraceutical Protocol with Fullscript

I collaborated with Fullscript to develop a nutritional protocol to personalize the approach in supporting individuals on OC. These supplements address nutrient depletions caused by oral contraceptives and offer additional support for hormone metabolism, gut health, and overall well-being:

  • Multivitamin/multimineral: Includes folate, zinc, selenium, vitamin C, vitamin A, vitamin E, and B complex. Recommended doses: minimum of 400 mcg folate, 100 mcg selenium, 15 mg zinc, and 500 mg vitamin C.
  • Magnesium bisglycinate: Recommended dosage of 200–400 mg daily.
  • Prebiotics fiber blend: 4–8 g daily to support gut health and hormone balance.
  • Iron bisglycinate: Recommended dosage of 25–30 mg every other day to prevent iron deficiency anemia.
  • Ashwagandha (Withania somnifera): Recommended dosage of 500 mg daily for stress management, hormonal balance, and mood improvement.

The Fullscript protocol details are available here.

 

Assessment Plan

We should begin to rethink our annual assessment to include a more comprehensive evaluation of the nutrition status, gut health, and microbiome status of patients taking OC. This starts with a comprehensive dietary assessment to identify and address potential deficiencies in essential nutrients affected by contraceptive use discussed above, as well as laboratory testing for nutrients such as folate, vitamin B12,  B6, iron and magnesium.

Additionally, assess gut health by noting symptoms of gastrointestinal distress and confirming consistent and daily bowel movements. Clinicians can also conduct more comprehensive evaluation of gut health by using tools like stool analysis to evaluate the diversity and composition of the gut microbiome. Monitoring these factors can identify imbalances and help guide dietary and nutraceutical recommendations.

 

Conclusion

Oral contraceptives are a useful tool for reproductive health, but like any medication can also cause risks and contribute to nutrient depletions and gut-related complications. More research is needed to fully establish mechanisms and determine clinical guidance. But by understanding these impacts, clinicians can better support people who choose to use these medications.

Oral contraceptives are just one piece of the puzzle when it comes to health. By considering all aspects of health – including diet, lifestyle, and medication use – we can help people who menstruate live healthier, happier lives.

 

References

  1. Baker JM, Al-Nakkash L, Herbst-Kralovetz MM. Estrogen-gut microbiome axis: Physiological and clinical implications. Maturitas. 2017;103:45-53. doi:10.1016/j.maturitas.2017.06.025. Link
  2. Balle C, Konstantinus IN, Jaumdally SZ, et al. Hormonal contraception alters vaginal microbiota and cytokines in South African adolescents in a randomized trial. Nat Commun. 2020;11(1):5578. Published 2020 Nov 4. doi:10.1038/s41467-020-19382-9. Link
  3. Basici S, Porcaro G. Counteracting side effects of combined oral contraceptives through the administration of specific micronutrients. Eur Rev Med Pharmacol Sci. 2022;26(13):4846-4862. doi:10.26355/eurrev_202207_29210. Link
  4. Berenson AB, Rahman M. Effect of hormonal contraceptives on vitamin B12 level and the association of the latter with bone mineral density. Contraception. 2012;86(5):481-487. doi:10.1016/j.contraception.2012.02.015. Link
  5. Brown J, Crawford TJ, Datta S, Prentice A. Oral contraceptives for pain associated with endometriosis. Cochrane Database Syst Rev. 2018;5(5):CD001019. Published 2018 May 22. doi:10.1002/14651858.CD001019.pub3
  6. Cooper DB, Patel P, Mahdy H. Oral Contraceptive Pills. [Updated 2022 Nov 24]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430882/
  7. Eyupoglu ND, Caliskan Guzelce E, Acikgoz A, et al. Circulating gut microbiota metabolite trimethylamine N-oxide and oral contraceptive use in polycystic ovary syndrome. Clin Endocrinol (Oxf). 2019;91(6):810-815. doi:10.1111/cen.14101. Link
  8. Eyupoglu ND, Ergunay K, Acikgoz A, Akyon Y, Yilmaz E, Yildiz BO. Gut Microbiota and Oral Contraceptive Use in Overweight and Obese Patients with Polycystic Ovary Syndrome. J Clin Endocrinol Metab. 2020;105(12):dgaa600. doi:10.1210/clinem/dgaa600. Link
  9. Hoeger KM, Dokras A, Piltonen T. Update on PCOS: Consequences, Challenges, and Guiding Treatment. J Clin Endocrinol Metab. 2021;106(3):e1071-e1083. doi:10.1210/clinem/dgaa839
  10. Hua X, Cao Y, Morgan DM, et al. Longitudinal analysis of the impact of oral contraceptive use on the gut microbiome. J Med Microbiol. 2022;71(4):10.1099/jmm.0.001512. doi:10.1099/jmm.0.001512. Link
  11. Judkins TC, Oula ML, Sims SM, Langkamp-Henken B. The effect of a probiotic on gastrointestinal symptoms due to menstruation in healthy adult women on oral contraceptives: randomized, double-blind, placebo-controlled trial protocol. Trials. 2022;23(1):481. Published 2022 Jun 10. doi:10.1186/s13063-022-06410-w. Link
  12. Krog MC, Hugerth LW, Fransson E, et al. The healthy female microbiome across body sites: effect of hormonal contraceptives and the menstrual cycle. Hum Reprod. 2022;37(7):1525-1543. doi:10.1093/humrep/deac094. Link
  13. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Estrogens and Oral Contraceptives. [Updated 2020 May 28]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK548539/
  14. Mahfouz MS, Elmahdy M, Ryani MA, et al. Contraceptive Use and the Associated Factors among Women of Reproductive Age in Jazan City, Saudi Arabia: A Cross-Sectional Survey. Int J Environ Res Public Health. 2023;20(1):843. Published 2023 Jan 2. doi:10.3390/ijerph20010843. Link
  15. McArthur JO, Tang H, Petocz P, Samman S. Biological variability and impact of oral contraceptives on vitamins B(6), B(12) and folate status in women of reproductive age. Nutrients. 2013;5(9):3634-3645. Published 2013 Sep 16. doi:10.3390/nu5093634. Link
  16. Prescott JD, Drake VJ, Stevens JF. Medications and Micronutrients: Identifying Clinically Relevant Interactions and Addressing Nutritional Needs. J Pharm Technol. 2018;34(5):216-230. doi:10.1177/8755122518780742. Link
  17. Shere M, Bapat P, Nickel C, Kapur B, Koren G. Association Between Use of Oral Contraceptives and Folate Status: A Systematic Review and Meta-Analysis. J Obstet Gynaecol Can. 2015;37(5):430-438. doi:10.1016/S1701-2163(15)30258-9. Link
  18. Smrekar K, Lodise NM. Combined Oral Contraceptive Use and Breast Cancer Risk: Select Considerations for Clinicians. Nurs Womens Health. 2022;26(3):242-249. doi:10.1016/j.nwh.2022.01.003. Link
  19. Teal S, Edelman A. Contraception Selection, Effectiveness, and Adverse Effects: A Review. JAMA. 2021;326(24):2507–2518. doi:10.1001
  20. Yong EL, Logan S. Menopausal osteoporosis: screening, prevention and treatment. Singapore Med J. 2021;62(4):159-166. doi:10.11622/smedj.2021036