Diabetes Forecast February 2005

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FOR GESTATIONAL

Research Profile

Hormonal Birth Control
A Gestational Diabetes Risk?
by Terri Kordella

Assiamira Ferrara, MD, PhD, believes certain hormonal birth control methods may increase the risk of developing gestational diabetes.	Assiamira Ferrara, MD, PhD Occupation Research Scientist Division of Research Kaiser Foundation Research Institute Professional Focus Hormonal birth control, gestational diabetes Outside Interests Travel, skiing, dinner with friends Research Funding ADA Research Award

Gestational diabetes affects about 7 percent of pregnant women each year. Gestational diabetes occurs only during pregnancy, when the body isn't able to make and use all the insulin it needs. Risk factors for gestational diabetes include obesity and a family history of diabetes.

Assiamira Ferrara, MD, PhD, believes there may be another risk factor for gestational diabetes, as well: past use of hormonal birth control such as Depo-Provera, Norplant, and certain forms of the pill. Ferrara and her team of researchers, as coordinated by Monique Hedderson, MPH, at the Kaiser Foundation Research Institute in Oakland, Calif., are using funds from an American Diabetes Association Research Award to determine if there is a link.

Birth Control Backgrounder

Women have many hormonal birth control options, so a little background is in order.

Hormonal birth control can work one of two ways. First, most forms of the pill contain an estrogen and a progestin. The estrogen keeps your ovaries from releasing eggs. Progestin thickens the mucous around the cervix, which helps prevent sperm from entering the uterus. And in case you do release an egg and it's fertilized, the progestin makes the uterus inhospitable to fertilized eggs. The egg will not be able to implant itself in the uterine wall and develop.

A second form of the pill, often referred to as the "mini-pill," contains only a progestin.

Depo-Provera is a shot of progestin that your doctor gives you every 3 months. Norplant, which is no longer available in the United States, consists of five rods that contain progestin. The rods are implanted under the skin of the upper arm and are good for several years. Norplant was taken off the market in the United States in 2002 after questions arose about expiration dates, but some women still have the rods implanted in their arms and rely on them for birth control. (The U.S. Food and Drug Administration says this is okay.)

Certain progestins have what doctors call "androgenic" effects on a woman's body: They behave much like male hormones called androgens. For example, they may increase your appetite and sex drive.

Progestins with the most androgenic effects are thought to be norgestrel (found in Lo/Ovral, Ovral-28, and other pills), levonorgestrel (found in Alesse, Levlen, Nordette, Triphasil, and other pills, as well as Norplant), norethindrone (found in Necon, Norinyl, Ovcon, and other pills, as well as the mini-pill, Micronor), and medroxyprogesterone (found in Depo-Provera). Other forms of progestin, such as norgestimate (found in Ortho Tri-Cyclen and other pills), are thought to have less androgenic effects.

Ferrara's study is focusing on high-androgenic progestins. Ferrara took a particular interest in the topic after seeing the results of earlier, smaller studies that linked hormonal birth control containing these progestins to type 2 diabetes. She wanted to delve deeper.

"One study of Native-American women found that those who used Depo-Provera had a higher risk of developing type 2," she says. "And in a study of Mexican-American women who developed type 2 diabetes after a pregnancy complicated by gestational diabetes, researchers found that many of the women used [progestin-only] Micronor when breast-feeding."

Researchers, including Ferrara, aren't sure exactly how these progestins actually raise the risk of gestational or type 2 diabetes. One theory is that they alter the way muscle cells use insulin and promote insulin resistance—even after you stop using them. Another theory is that progestins contribute to weight gain by increasing appetite. Weight gain can lead to insulin resistance and diabetes.

Sorting Options

Ferrara's study involves some data-crunching. Her team is reviewing the medical records of 660 women in the Kaiser health plan who were pregnant between 1996 and 1998, half of whom had gestational diabetes.

"We'll review all their medical records for the 6 years before their pregnancies and see what kind of prescriptions they had, what kinds of hormonal contraceptives they used, how long they used them, and if they switched from one kind to another. Then we'll analyze and compare the records to see if those who had gestational diabetes were more likely to have used progestins with high androgenic effects," Ferrara says.

If Ferrara's research reveals a link between these hormonal contraceptives and an increased risk of gestational diabetes, it may help doctors sort through and recommend the safest forms of birth control for women who are already at risk for gestational diabetes.

"For example, if you have a family history of diabetes, are overweight, had gestational diabetes in a previous pregnancy, or belong to a minority ethnic group, you might be better off using a different kind of hormonal contraceptive, or using entirely different methods of birth control," she says.

She adds that women can lower their risk of gestational diabetes by exercising, avoiding weight gain, and watching their diet. "Until we know for sure about the contraceptives, it's best to cut as many risk factors as possible."