At InsideTracker, we're often asked if hormonal contraceptives can affect female biomarkers. The answer? Yes. 

Like any other medication, hormonal contraceptives (pills, patches, rings, IUDs, implants, and injections) interfere with different pathways and processes in the body. Naturally, there can be some unintended residual effects, like nudging some blood biomarkers outside of the normal reference range. Some of these biomarker changes may be attributed to your contraceptive use, while others may be a combination of factors. And, some forms of hormonal contraceptives affect certain markers, while others do not. InsideTracker’s women’s health insights account for contraceptive use and type to give you personalized insights as to how this medication may influence your blood biomarkers.

Here, we give a broad overview on how hormonal contraceptives impact nine blood biomarkers. 

Low dehydroepiandrosterone-sulfate (DHEAS)

DHEAS levels are significantly lower for oral contraceptive pill (OC) users than non-OC users. [1,2] DHEAS is a molecule that is synthesized into the sex hormones estradiol and testosterone and is essential for energy, muscle and bone health, and sexual function for both men and women. The reduction in DHEAS by OC is potentially due to the suppression of androgens made by the adrenal glands, combined with higher cortisol production. DHEAS levels begin to drop soon after beginning OC and, depending on the duration of OC use, can take quite some time to increase once OC use is discontinued. Of note, OC is the only form of a hormonal contraceptive with evidence to suggest a relationship to lower DHEAS levels. DHEAS levels also naturally decline after the mid-20s. [1,2]  

Elevated sex hormone binding globulin (SHBG)

SHBG can be elevated in people using combined contraceptives that contain both estrogen and progesterone, like an OC, patch, or vaginal ring. [2,3] SHBG binds to testosterone and reduces its bioavailability. And the influx of exogenous estrogens from birth control results in a dose-related increase in SHBG production by the liver.

Studies show that peak SHBG levels can be reached in as little as three weeks after beginning a combined contraceptive and, subsequently, can fall just as quickly after stopping use. Since increases in SHBG are dose-dependent, forms with lower doses of synthetic estrogens result in the lowest increase in SHBG. Conversely, forms with higher dosages (like the patch and the ring) result in the largest increases. Progestin-only contraceptives like the IUD, implant, and injection have not been shown to correlate with an increase in SHBG.

Low testosterone

Testosterone production is also suppressed while taking an OC, typically by up to 50%.² Researchers propose this decrease is due to suppression of testosterone created in the ovaries, suppression of testosterone created in the adrenal glands, and increased SHBG levels. An important note here is how important testosterone is, not just for men – women also require testosterone for energy, muscle and bone health, and a healthy libido.

Elevated cortisol

Women on birth control may have elevated cortisol levels due to the changes in the adrenal glands. [2]  

Women taking OCs are more likely to have elevated cortisol levels. The use of OCs suppresses the production of androgens—like testosterone—from the adrenal glands. Therefore, the body may produce more cortisol to funnel the chemical byproducts that would otherwise go toward making androgens. This relationship is seen only in OC users, not in other forms of hormonal contraceptives. Females with elevated cortisol levels should also consider lifestyle changes such as increasing sleep, reducing stress, meditation, and ensuring adequate calorie intake. 

Elevated hsCRP

Elevated hsCRP—a marker of inflammation— levels are also associated with estrogen-containing contraceptive use. [4] Low-grade inflammation as a result of the use of estrogens may predispose individuals to a higher inflammatory response to physical activity, especially in athletes. [5] A concerted effort to combat inflammation with a diet high in antioxidants like vitamins A, C, and E, as well as ample healthy fats and adequate sleep, can help to mitigate the damage of inflammation.

Low vitamin B12

OC use is associated with lower serum vitamin B12 concentrations, even when controlling for intake through diet.  [6,7]

Researchers aren’t clear on whether OC results in a disruption of vitamin B12 absorption, recycling, or storage. Vitamin B12 is a critical nutrient due to its role in DNA and red blood cell synthesis, lipid and carbohydrate metabolism, and brain and nervous system function. Vitamin B12 levels fluctuate throughout the female lifespan, but it is particularly critical for females during their reproductive years. OC users may present with low levels of blood B12 but be asymptomatic. For this reason, if you have lower vitamin B12 and you are taking oral contraceptives, focus on increasing your intake of vitamin B12 rich foods like meat, eggs, and dairy, and monitor your levels. 

This association does not appear with other forms of hormonal contraceptives besides the pill.

Estradiol

Estradiol fluctuates notably throughout the course of a woman’s monthly menstrual cycle, and it is normal for levels to be low during the first half (follicular phase) of the cycle and much higher during ovulation and the second half (luteal phase) of the cycle.  Use of any hormonal contraceptives can blunt the changes in estradiol over the course of a cycle. It is common for contraceptive users to have lower than expected estradiol levels, especially during the luteal phase. [8-10]

However, InsideTracker’s optimal zones for estradiol take into account your hormonal contraceptive use, as reported in your health profile. This means that while hormonal contraceptives can lower your estradiol, your InsideTracker results will show you if your levels are optimized for you as a contraceptive user, or if they could still use improvement. 

Progesterone

Progesterone increases dramatically in the second half of the menstrual cycle in response to ovulation. Hormonal contraceptives can prevent this increase, leading to lower progesterone levels during the luteal phase in contraceptive users. Like with estradiol, your optimal zones take into account your reported hormonal contraceptive use. So while progesterone may be lower than in someone not using hormonal contraceptives, your InsideTracker progesterone results will show optimized progesterone levels for women on hormonal contraceptives. [11,12]

Cholesterol markers

Hormonal contraceptives have been shown to impact cholesterol markers like triglycerides, LDL and HDL cholesterol, though different forms can move these markers in different directions. For example, combined contraceptives like the pill and the patch have been associated with an increase in HDL cholesterol, while the progestin-only contraceptive implant and injection are correlated with lower levels of HDL cholesterol. [13,15]

Increased triglycerides are associated with the pill and patch only, while no significant association has been shown between other forms of hormonal contraceptives and triglyceride levels. Most hormonal contraceptives do not impact LDL cholesterol, however evidence suggests that the implant may have a protective, lowering effect on LDL levels. [13]

Understand how hormonal contraceptive use is impacting your biomarkers

Are you curious how your birth control is affecting your biomarkers? InsideTracker can help you identify and monitor any effects that your birth control may have on your biomarkers, including all the one’s discussed here. You’ll also receive food, supplement, and lifestyle recommendations to help optimized any unoptimized biomarker. Understanding various impacts of the different forms can be useful when prioritizing your own biomarkers and when talking with your physician about what contraceptive is right for you.

Ashley Reaver, MS, RD, CSSD

References:

[1] Murphy, Ana Alvarez, et al. "Effect of low-dose oral contraceptive on gonadotropins, androgens,and sex hormone binding globulin in nonhirsute women." Fertility and sterility 53.1 (1990): 35-39.

[2] Zimmerman, Y., et al. "The effect of combined oral contraception on testosterone levels in healthy women: a systematic review and meta-analysis." Human reproduction update20.1 (2014): 76-105.

[3] Raps, M., et al. "Sex hormone‐binding globulin as a marker for the thrombotic risk of hormonal contraceptives." Journal of Thrombosis and Haemostasis10.6 (2012): 992-997.

[4] Sørensen, Cecilie J., et al. "Combined oral contraception and obesity are strong predictors of low-grade inflammation in healthy individuals: results from the Danish Blood Donor Study (DBDS)." PloS one9.2 (2014): e88196.

[5] Cauci, Sabina, Maria Pia Francescato, and Francesco Curcio. "Combined oral contraceptives increase high-sensitivity C-reactive protein but not haptoglobin in female athletes." Sports Medicine47.1 (2017): 175-185.

[6] McArthur, Jennifer O., et al. "Biological variability and impact of oral contraceptives on vitamins B6, B12 and folate status in women of reproductive age." Nutrients5.9 (2013): 3634-3645.

[7] Berenson, Abbey B., and Mahbubur Rahman. "Effect of hormonal contraceptives on vitamin B12 level and the association of the latter with bone mineral density." Contraception86.5 (2012): 481-487.

[8] 

[8] Berenson, A. B., & Rahman, M. (2012). Effect of hormonal contraceptives on vitamin B12 level and the association of the latter with bone mineral density. Contraception, 86(5), 481–487. 

[9] Mishell, D. R., Jr, Thorneycroft, I. H., Nakamura, R. M., Nagata, Y., & Stone, S. C. (1972). Serum estradiol in women ingesting combination oral contraceptive steroids. American journal of obstetrics and gynecology, 114(7), 923–928. 

[10] Darney, P. D., Taylor, R. N., Klaisle, C., Bottles, K., & Zaloudek, C. (1996). Serum concentrations of estradiol, progesterone, and levonorgestrel are not determinants of endometrial histology or abnormal bleeding in long-term Norplant implant users. Contraception, 53(2), 97–100.  

[11] Sarkola, T., Mäkisalo, H., Fukunaga, T., & Eriksson, C. J. (1999). Acute effect of alcohol on estradiol, estrone, progesterone, prolactin, cortisol, and luteinizing hormone in premenopausal women. Alcoholism, clinical and experimental research, 23(6), 976–982.

[12] Darney, P. D., Taylor, R. N., Klaisle, C., Bottles, K., & Zaloudek, C. (1996). Serum concentrations of estradiol, progesterone, and levonorgestrel are not determinants of endometrial histology or abnormal bleeding in long-term Norplant implant users. Contraception, 53(2), 97–100. 

[13] Piltonen, T., Puurunen, J., Hedberg, P., Ruokonen, A., Mutt, S. J., Herzig, K. H., Nissinen, A., Morin-Papunen, L., & Tapanainen, J. S. (2012). Oral, transdermal and vaginal combined contraceptives induce an increase in markers of chronic inflammation and impair insulin sensitivity in young healthy normal-weight women: a randomized study. Human reproduction (Oxford, England), 27(10), 3046–3056. 

[14] Merki-Feld, G. S., Imthurn, B., Rosselli, M., & Spanaus, K. (2011). Implanon use lowers plasma concentrations of high-molecular-weight adiponectin. Fertility and sterility, 95(1), 23–27. 

[15] Berenson, A. B., Rahman, M., & Wilkinson, G. (2009). Effect of injectable and oral contraceptives on serum lipids. Obstetrics and gynecology, 114(4), 786–794.