The Impact of Combined Hormonal Birth Control on Insulin Sensitivity and Inflammation - FACTS (2023)

By: Jessica Kerpez

Editor’s Note: This week, we feature a research review summarized by Jessica Kerpez, a medical student and former FACTS elective participant. While previous studies have identified decreased insulin sensitivity in women taking oral contraceptives, this was the first paper to evaluate how all three forms of contraceptives might impact inflammatory markers, lipid markers, and insulin levels


With approximately 65% of women aged 15 to 49 currently using contraception[1] it is important to be aware of the broad effects that hormonal birth control can have on a woman’s health. This study by Piltonen et al was designed to evaluate three different administration routes of contraception, including transdermal, oral, and vaginal ring, and how these routes might influence markers of inflammation and insulin sensitivity.[2] Increased inflammation and reduced insulin sensitivity are risk factors that can lead to the development of different diseases, including Type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). [3]

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The results of previous trials suggest oral combined contraceptives worsen glucose metabolism, whereas transdermal and vaginal contraceptives have little to no effect. Furthermore, the effect of combined contraceptives on lipid metabolism has been unclear, although the majority of studies indicate an increase in triglyceride and high-density lipoprotein cholesterol (HDL-C) levels following use of oral and transdermal contraceptives. [4] Prior research also identified an association between oral contraceptives (OCPs) and CVD, although the risk may be diminished upon discontinuation of OCPs. [5] The development of CVD can also be influenced by C-reactive protein (CRP,) a liver inflammatory marker, which is considered to be an independent risk factor for CVD. Few studies exist evaluating the effect of combined contraceptives on CRP levels.[6] Piltonen et al therefore designed the study to further investigate the mechanism by which all three forms of hormonal birth control could influence inflammatory markers, lipid markers, and insulin levels. [1]

“The results of previous trials suggest oral combined contraceptives worsen glucose metabolism, whereas transdermal and vaginal contraceptives have little to no effect.”


The study evaluated a total of 54 healthy Caucasian women (aged 20-33) at Oulu University Hospital, Finland between September 2008 and December 2010. Participants had a BMI between 17.9-26.4 kg/m² with no medication use and regular menstrual cycles. The women were randomly assigned in equal numbers to one of three preparations: a combined oral contraceptive pill, a transdermal contraceptive patch, or a contraceptive vaginal ring. Blood pressures and glucose tolerance levels were measured at baseline. Normal ovarian function was verified via ultrasound. Exclusion criteria included impaired fasting glucose (IFG) or IGT, T2DM, type 1 diabetes, alcohol abuse, cigarette smoking, and any contraindications regarding use of combined contraceptives and lactation.

Fasting blood samples and levels of serum 17-hydroxyprogesterone, androstenedione, testosterone, sex hormone binding globulin (SHBG), total cholesterol, LDL/HDL, triglycerides, and high sensitivity CRP were collected at baseline, five weeks, and nine weeks. The oral glucose tolerance test was performed via a 75 g load of glucose, with IFG diagnosed at a glucose range of 6.1-6.9 mmol/L and IGT diagnosed when glucose levels at two hours were between 7.8-11.0 mmol/L. The study then plotted insulin and glucose levels using the area under the curve (AUC).

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Mean age, BMI, waist-to-hip ratio, and blood pressure were comparable at the end of the study compared to the beginning, except a very slight BMI increase from 21.6 kg/m2 to 22.0 kg/m² in the transdermal patch group. Serum levels of 17-OHP and androstenedione decreased significantly across all study groups. Testosterone levels were unchanged in the oral and vaginal ring groups but increased in the transdermal patch group. Serum levels of SHBG increased significantly over time. Fasting serum levels of insulin increased significantly from baseline for all three groups. The AUC of insulin also rose significantly for the oral (P ≤ 0.030) and transdermal (P ≤ 0.041) combined contraceptives, and a slight rise was observed in the vaginal ring group (P ≤ 0.013). In the transdermal patch group, serum levels of C-peptide rose from baseline to nine weeks, but this was not observed in the other formulations studied. The fasting insulin sensitivity index decreased in all three study groups.

Fasting serum levels of insulin increased significantly from baseline for all three groups (and) … the fasting insulin sensitivity index decreased in all three study groups.”

Serum total cholesterol remained unchanged in all three groups, although triglyceride levels and HDL increased significantly. LDL cholesterol concentration rose significantly only in the oral contraceptive group. The total concentration of CRP was found to rise in all three study groups at 9 weeks, excluding five women from the analysis. The increase in SHBG levels was smaller in the vaginal ring group compared to the other two groups. The change in fasting glucose was highest in the vaginal ring group.

The Impact of Combined Hormonal Birth Control on Insulin Sensitivity and Inflammation - FACTS (1)

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This research was the first to evaluate how all three routes of hormonal birth control, oral, transdermal, and vaginal, can influence both insulin levels and inflammatory markers. Some of the key observations to note are that serum levels of SHBG increased across all three study groups, leading to a decrease in the free androgen index. Another key observation was that even though the fasting serum glucose levels were consistent at nine weeks, the insulin sensitivity decreased in all three study groups. Consistent with these findings, previous studies have also demonstrated decreased insulin sensitivity in the oral contraception group. However, this study was important as it was the first study to show this effect also applies to both transdermal and vaginal contraception. Furthermore, it also shed light on the effects of different types of hormonal birth control on cholesterol and triglyceride levels, largely unclear prior to the study; increased serum levels of HDL and triglycerides were observed in all three groups, whereas serum cholesterol was somewhat stable over time.

Combined contraceptives have these effects due to estrogen decreasing insulin sensitivity whereas progestin increases insulin response in conjunction with estrogen use. Estrogen also increases levels of HDL and decreases LDL, while progestin has the opposite effect.[6] It is important to look at an increase in HDL, as this is considered an independent inverse risk factor for diseases including CVD even when LDL levels are low. Elevated levels of the inflammatory marker CRP were found to increase in all study groups, a prognostic marker for the development of CVD [7].

The results found that all three formulations of combined hormonal birth control generally have an adverse effect on glucose metabolism and have the potential to cause chronic inflammation. This is noteworthy as it is the first study to demonstrate that not only oral, but also transdermal and vaginal routes of administration have these effects. Worsening insulin resistance and increased insulin levels have been implicated in the subsequent increase in CVD and type 2 diabetes mellitus. Therefore, the use of combined contraceptives needs to be used with caution, particularly in those patients with pre-existing conditions, including but not limited to obesity, type 2 diabetes, CVD, or an androgen deficiency disorder. Women should be aware of these effects and discuss with their doctor the full spectrum of options to meet their individual family planning or health care needs, including fertility awareness-based methods (FABMs).

Fasting serum levels of insulin increased significantly from baseline for all three groups (and) … the fasting insulin sensitivity index decreased in all three study groups.”

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Disadvantages of the study include the 20% drop-out rate and the fact that the study was not blinded, which could impact the significance of the data collected. In future studies, it would be imperative to conduct a double-blind study with a larger sample size and higher retention rate. Furthermore, it would be beneficial to expand the cultural diversity of the subject population beyond Caucasian women, especially considering that women of different ethnicities have varying responses in their insulin and inflammatory marker levels. [8] Future studies should identify safe ranges for insulin or inflammatory marker levels to determine the point at which it may no longer be safe for women to continue using contraceptives and evaluate and suggest alternatives. FABMs are a safe alternative for family planning, with a number of different methods available for women and couples to use. For couples with limited time and resources to learn a method, or those that desire to learn a method online, the Billings Ovulation Method or the Standard Days Method may be valuable options. For women with irregular cycles, the Creighton Model, the Sympto-Thermal Method, or the Marquette Model may be a good fit; several of these methods offer a way to cross-check observations and have established protocols to address medical issues.


[1] Daniels K, Mosher WD, Jones J. Contraceptive methods women have ever used: United States, 1982–2010. National Health Statistics Reports; no 62. Hyattsville, MD: National Center for Health Statistics. 2013.
[2] Piltonen T, Puurunen J, Hedberg P, et al. 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. Hum Reprod. 2012;27(10):3046-3056. doi:10.1093/humrep/des225
[3] Haffner SM. Pre-diabetes, insulin resistance, inflammation and CVD risk. Diabetes Res Clin Pract. 2003 Jul;61 Suppl 1:S9-S18. doi: 10.1016/s0168-8227(03)00122-0. PMID: 12880690.
[4] Cagnacci A, Ferrari S, Tirelli A, Zanin R, Volpe A. Route of administration of contraceptives containing desogestrel/etonorgestrel and insulin sensitivity: a prospective randomized study. Contraception. 2009;80(1):34-39. doi:10.1016/j.contraception.2009.01.012
[5] Baillargeon JP, McClish DK, Essah PA, Nestler JE. Association between the current use of low-dose oral contraceptives and cardiovascular arterial disease: a meta-analysis. J Clin Endocrinol Metab. 2005;90:3863-3870.
[6] Mantovani A, Garlanda C, Doni A, Bottazzi B. Pentraxins in innate immunity: from C-reactive protein to the long pentraxin PTX3. J Clin Immunol. 2008;28:1 – 13.
[7] Isomaa B, Almgren P, Tuomi T, et al. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care. 2001;24(4):683-689. doi:10.2337/diacare.24.4.683
[8] White T, Jain JK, Stanczyk FZ. Effect of oral versus transdermal steroidal contraceptives on androgenic markers. Am J Obstet Gynecol. 2005;192(6):2055-2059. doi:10.1016/j.ajog.2005.02.067



How does birth control affect insulin resistance? ›

Many hormonal contraceptives have been associated with changes in carbohydrate metabolism. Alterations may include decreased glucose tolerance and increased insulin resistance, which are risk factors for Type 2 diabetes mellitus and cardiovascular disease.

Can hormonal birth control cause inflammation? ›

Inflammation. Inflammation , which is a common denominator in essentially all chronic disease , is also more likely with birth control pills.

Does OCP increase insulin resistance? ›

Diabetes & birth control at a glance

However, the estrogen in birth control pills can raise blood glucose levels, which increase a diabetic's resistance to insulin and may require an adjustment in the insulin she receives.

How does birth control affect blood sugar? ›

Diabetes mellitus (sugar diabetes)—Use of oral contraceptives may cause an increase, usually only a small increase, in your blood sugar and usually does not affect the amount of diabetes medicine that you take.

What hormone can cause insulin resistance? ›

Cortisol, the “stress hormone,” is vital to regulating your blood sugar levels (by increasing them) and turning food into energy. Excess cortisol can counteract the effects of insulin, causing insulin resistance.

What birth control is best for insulin resistance? ›

Per the University of Colorado, the increased need for insulin may be attributed to the estrogen used in the Pill. Birth control pills that use synthetic estrogen and norgestimate (a type of progestin hormone) are often recommended for people with diabetes.

What hormone is responsible for inflammation? ›

High levels of prostaglandins are produced in response to injury or infection and cause inflammation, which is associated with the symptoms of redness, swelling, pain and fever. This is an important part of the body's normal healing process.

What hormone increases inflammation? ›

Along with estrogen, cortisol is one of the main hormones that is correlated with long-term chronic inflammation and overactive immune system.

What hormone controls inflammation? ›

Cortisol: One of the primary roles of cortisol in the body is to reduce inflammation and control your body's immune response.

What causes insulin resistance to increase? ›

What Causes Insulin Resistance? It isn't clear exactly what causes insulin resistance, but a family history of type 2 diabetes, being overweight (especially around the waist), and being inactive all can raise the risk. You do not have to be overweight to have insulin resistance.

Does estrogen make you insulin resistant? ›

Estrogen deficiency or impaired estrogen signaling is associated with insulin resistance and dysregulation of metabolic homeostasis, thus contributing to the development of T2D and obesity in both human and animal models (31–33).

What are 3 effects of the OCP? ›

Adverse Effects

The most common adverse effect of combined oral contraceptive pills is breakthrough bleeding. Women will also complain of nausea, headaches, abdominal cramping, breast tenderness, and increased vaginal discharge or decreased libido. Nausea can be avoided by taking the medication at night before sleep.

How do you increase insulin sensitivity? ›

Here are 14 natural, science-backed ways to boost your insulin sensitivity.
  1. Get more sleep. A good night's sleep is important for your health. ...
  2. Exercise more. ...
  3. Reduce stress. ...
  4. Lose a few pounds. ...
  5. Eat more soluble fiber. ...
  6. Add more colorful fruit and vegetables to your diet. ...
  7. Cut down on carbs. ...
  8. Reduce your intake of added sugars.

Do hormones control blood sugar levels? ›

Glucagon and insulin are both important hormones that play essential roles in regulating your blood glucose (sugar). Both hormones come from your pancreas — alpha cells in your pancreas make and release glucagon, and beta cells in your pancreas make and release insulin.

Which contraceptive increases the risk of diabetes? ›

Combined estrogen-progestin high-dose oral contraceptives increase the risk of impaired glucose tolerance which is estimated at approximately 12% of oral contraceptive current users.

Does high estrogen cause high insulin? ›

Data from population studies showed that estrogen was associated with lower fasting glucose and insulin levels (3,8–10), but its use was related to a rise in 2-h insulin and glucose levels (8,11). The association between risk of type 2 diabetes and postmenopausal estrogen use is not clear.

What hormones affect insulin processes? ›

Insulin works in tandem with glucagon, another hormone produced by the pancreas. While insulin's role is to lower blood sugar levels if needed, glucagon's role is to raise blood sugar levels if they fall too low.

Can hormones affect insulin levels? ›

Growth Hormone is released from the pituitary, which is a part of the brain. Like cortisol, growth hormone counterbalances the effect of insulin on muscle and fat cells. High levels of growth hormone cause resistance to the action of insulin.

Does progestin cause insulin resistance? ›

Several studies have shown that high concentration of progesterone is related to abnormal glucose metabolism, including a high level of plasma glucose, increased insulin resistance, elevated insulin release and apoptosis of pancreatic β cells (13, 14, 15, 16).

What is the fastest way to reverse insulin resistance? ›

Fasting for at least 16 hours gives the body a chance to rest and allows blood levels of insulin to drop significantly. Not only does this help burn fat, it can also lower your risk of disease, particularly diabetes and pre-diabetes.

Does birth control help with insulin resistance PCOS? ›

Birth Control Pills May Reduce Type 2 Diabetes Risk for People with PCOS.

Can female hormones cause inflammation? ›

Estrogens influence immune and inflammatory processes, as revealed by increased inflammatory responses to infection and sepsis and higher rate of autoimmune diseases in women when compared to men as well as by the variation of chronic inflammatory disease activity with the menstrual cycle, pregnancy, and menopause [9, ...

Does estrogen increase or decrease inflammation? ›

Estrogen has been described to suppress vascular inflammation by downregulation of proinflammatory molecules, including cytokines and adhesion molecules. Inflammatory response has also been shown to vary significantly according to the estrous cycle in rodents.

What is the number one cause of inflammation? ›

The most common reasons for chronic inflammation include: Autoimmune disorders, such as lupus, where your body attacks healthy tissue. Exposure to toxins, like pollution or industrial chemicals. Untreated acute inflammation, such as from an infection or injury.

Can birth control cause high insulin? ›

Hormonal birth control can impact insulin resistance and therefore lead to higher blood glucose levels, but hormones affect everyone differently. Some people already see an example of this when they experience higher insulin needs or higher blood sugar levels right before their period.

How do I balance my hormones with insulin resistance? ›

14 Natural Ways to Improve Your Insulin Sensitivity
  1. Get more sleep. A good night's sleep is important for your health. ...
  2. Exercise more. ...
  3. Reduce stress. ...
  4. Lose a few pounds. ...
  5. Eat more soluble fiber. ...
  6. Add more colorful fruit and vegetables to your diet. ...
  7. Cut down on carbs. ...
  8. Reduce your intake of added sugars.

What hormones cause insulin release? ›

Insulin release is stimulated by GH, cortisol, PRL, and the gonadal steroids. It is decreased by PTH. The effects of thyroid hormones are more variable. Epinephrine inhibits insulin release.

Does estrogen increase insulin? ›

Estrogen Improves Insulin Sensitivity and Suppresses Gluconeogenesis via the Transcription Factor Foxo1 - PMC.

Can you have inflammatory and insulin resistance PCOS? ›

PCOS is commonly associated with increased inflammation and insulin resistance, and a WFKD has been shown to have very potent effects reducing both of these.

Does PCOS increase insulin sensitivity? ›

This lifelong health condition continues far beyond the child-bearing years. Women with PCOS are often insulin resistant; their bodies can make insulin but can't use it effectively, increasing their risk for type 2 diabetes.

Does PCOS always cause insulin resistance? ›

Not all patients with PCOS have insulin resistance, and insulin resistance is not a part of the formal diagnostic criteria for PCOS. But your insulin levels, PCOS, and your body's ability to use insulin are all linked.

Does estrogen and progesterone cause insulin resistance? ›

Estradiol and progesterone were positively associated with insulin resistance and should be considered in studies of insulin resistance among premenopausal women.

How do you balance insulin cortisol and estrogen? ›

While cortisol is an important hormone, chronically high levels may lead to conditions such as obesity, heart disease, and diabetes.
Here are some lifestyle changes that may help manage cortisol levels:
  1. Optimize sleep. ...
  2. Exercise regularly. ...
  3. Practice mindfulness. ...
  4. Maintain a moderate body weight. ...
  5. Eat a balanced diet.

What is insulin resistance symptoms in females? ›

There are some signs of insulin resistance that your doctor may look for. These includes a waistline over 40 inches in men, and a waistline over 35 inches in women. Skin tags or patches of dark velvety skin called acanthosis nigricans. A blood pressure reading of 130 over 80 or higher.

Can stress cause insulin resistance? ›

If you're feeling stressed, your body releases stress hormones like cortisol and adrenaline. This should give you an energy boost for a 'fight or flight' response. But the hormones actually make it harder for insulin to work properly, known as insulin resistance.


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2. New Paradigms In Understanding PCOS: Impact of the Microbiome
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3. How Does Hormonal Birth Control Actually Work and What Are The Most Common Side Effects?
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4. The Impact & Side Effects of Hormonal Birth Control
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5. How Estrogen & Progesterone Levels affect Insulin Sensitivity with Karen Martel
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6. PCOS Q&A: TTC, Environmental Factors, Ovulation, Birth Control, Weight Loss and more!
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