Woman holding a pack of contraceptive pills

Steroids are often viewed with a double standard. When athletes use performance enhancers, we see it as highly unacceptable. They are stripped of their titles and medals, and their entire futures are affected. Yet millions of women worldwide use oral contraceptives, prescriptions for which are quite easy to come by.

Since its introduction in the 1960s, one of the biggest debates about oral contraceptives has been whether their benefits outweigh the associated risks. It most certainly appears that way for our risk of type 2 diabetes.

DNA changes in the SHBG gene that controls active steroid hormone levels in our blood can genetically predispose one to type 2 diabetes. But, oral contraceptives just might mitigate this risk.

Oral contraceptives in action

Combination oral contraceptives contain two hormones, estrogen and progesterone. Estrogen is the primary sex steroid in females, but it is also present in the blood of men. In females, it is essential for the development of secondary sexual characteristics. In males, it plays a role in sexual functions, including libido and sperm production.

Once released into the bloodstream by the ovaries (or the adrenal gland in men), estrogen simply diffuses into target cells. It turns on a wide range of genes that control anything from water retention to the breakdown of sugars and fats. Oral contraceptives therefore can impact a whole range of physiological functions, one of which is blood sugar.

Estradiol and blood sugar

Elevated estradiol levels increase the risk of abnormally high blood sugar levels and type 2 diabetes in both men and women. DNA changes in the SHBG gene also influence our susceptibility to diabetes.

Sex hormone-binding globulin (SHBG) is a protein the controls the levels of free estrogen in our blood, facilitating both its transport and uptake. According to the free sex hormone hypothesis, only the unbound (free) estrogen is biologically active. This means that changes in SHBG levels can affect the availability of estrogen.

Two SHBG variants (rs6259 A and rs1799941 A) result in higher blood levels of SHBG, and a significantly lower risk of type 2 diabetes. However, the rs6257 C variant results in 10% lower SHBG levels, increasing the risk of type 2 diabetes.

SHGB gene variants influence the risk of diabetes

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Reduced SHBG levels are indicative of one’s susceptibility to type 2 diabetes, because it can affect the availability of active estrogen in our blood. Supporting this notion, women with extremes in estrogen levels (higher than, or lower than, normal) are at higher risk of insulin resistance.

Insulin resistance is when the body stops responding to the insulin hormone that regulates blood sugar levels. It is a symptom of both obesity and pre-diabetes, but often goes undetected until it develops into type 2 diabetes.

Furthermore, estrogen appears to protect the survival of insulin-producing beta cells in the pancreas, and increases the production of SHBG. Studies also show that hormone replacement therapy improves control of blood sugar, and increases insulin sensitivity in diabetic postmenopausal women.

Benefits of oral contraceptives?

The relationship between diabetes, estrogen and SHBG is far from simple. But maybe we could speculate that oral contraceptives would benefit women with inherently low SHBG levels; those who are genetically susceptible to type 2 diabetes.

We are entering an era of personal genomics, where food, exercise, medications, and even birth control use can be personalized to match the unique genome of an individual. It will certainly be interesting to witness the next phase in the evolution of this widely used steroid.

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