Ronald Burkman, obstetrician/gynecologist

As the world marks half a century of oral contraceptives, this doctor probes the effects of an enduring biomedical touchstone, "the pill." Interview by Tanya Lewis

March 31, 2012

Courtesy of Ronald Burkman

Few things have transformed the role of women in society as profoundly as the oral contraceptive pill. First introduced as the drug Enovid, approved by the U.S. Federal Drug Administration in 1961, “the pill” prevents pregnancy by providing a constant supply of estrogen and progesterone, blocking the hormones that lead to ovulation. About 85 percent of women in the U.S. will take some version of the drug for an average of five years.

During much of the drug’s 50-year history, Ronald Burkman has investigated its risks and benefits. Women’s reproductive health seems an unlikely interest for the gray-haired and mild-mannered Burkman, a professor of obstetrics and gynecology at Tufts University School of Medicine. But beneath his clinical cloak lies a deeper motivation, one grounded in issues of unwanted pregnancy and overpopulation. His scientific papers navigate the maze of literature linking oral contraceptives to blood clots, stroke, and heart attack. The cardiovascular risks mostly plagued early hormone-heavy versions of the pill, Burkman concludes, though high blood pressure and smoking noticeably inflate the dangers. Yet the pill’s non-contraceptive benefits—such as staving off certain forms of cancer—outweigh its hazards, he believes.

Burkman spoke during a seminar entitled “Fifty Years of the Pill” at the February 2012 meeting of the American Association for the Advancement of Science in Vancouver, Canada. SciCom’s Tanya Lewis sat down with him afterward to find out where the science of this “wonder drug” stands. 

What interested you in studying contraception?

The significant public health impact. There are about 34 million unintended, unplanned pregnancies that occur each year, primarily in developing countries. Not having contraception has a significant impact on maternal mortality. If you’re in some countries in sub-Saharan Africa, your lifetime risk of dying in pregnancy is one in 30. Your lifetime risk of dying in this country is less than 10 per 100,000.

In your talk, you spoke about the fairly minimal cardiovascular risks from oral contraceptives. Are some drugs riskier than others?

People have looked at this, but no one has a lot of data on continuous use versus the usual intermittent use. Even with drospirenone [a synthetic hormone found in some oral contraceptives, associated with a higher risk of arterial blood clots], it becomes a question of how much risk you’ll accept. As a medical practitioner, I give my patients information about the risk, and it’s their choice. They may say, ‘Well, I really like drospirenone, because it helps me with PMDD [postmenopausal disphoric disorder].’ And they don’t want to take Prozac for depression, so they are willing to accept a possible increased risk of blood clots because there is the antidepressant benefit in addition to contraception. So everything is a balancing act.

"Are male contraceptive methods going to be as widespread as the pill for women was when it was first introduced? The market’s saturated."

Some studies have suggested the pill carries cancer risks.

One or two cancers may be increased by the pill—benign and malignant liver tumors—but those occur at one per million or one per two million, so it’s not a big public health issue. We’ve certainly been looking at women on the pill and the risk of cervical cancer, and there’s some evidence that it might occur, but again, it doesn’t go immediately to serious cervical cancer. But breast cancer? Not a lot of issue there. A study that I was involved in looked at women of reproductive age and identified no increased risk of breast cancer. But we showed that there are protective effects against endometrial and ovarian cancer.

Are there other health benefits of oral contraceptives?

There are a variety of reasons for oral contraceptives to be used in a non-contraceptive way: treatment of endometriosis [a disorder where cells of the uterus grow in other areas of the body], irregular menstrual cycles, and dysmenorrhea [painful periods].

[Speakers at the AAAS meeting mentioned other benefits: decreased blood loss and anemia, less acne, fewer ectopic pregnancies, decreased incidence of ovarian cysts, possible increase in bone density, and possible protection against pelvic inflammatory disease.]

Are these benefits associated with long-term use or short-term use?

One year of use does provide benefit; more prolonged use provides additional benefit.

So would you advise all women to take the pill for their health?

Putting healthy women on any drug to say that it has a health benefit becomes a potential issue. But the reality is, a lot of people use the pill anyway for contraception.

Some people say the pill causes weight gain. Is this true?

The data are pretty consistent: it does not cause any weight gain.

Could the synthetic hormones in the pill affect other hormones in the body?

All contraceptive hormones will affect other hormones to some extent. That’s how they work. The problem is, you can see blood levels of almost anything vary, but you have to attach it to something clinically. And what we don’t know is whether I will see a lot of variation if I measure those things in you over time. I think the problem with trying to attach a clinical syndrome to something is fraught with hazard. It’s like throwing darts on a dartboard and hoping you hit something.

Does the pill affect mood?

It varies from individual to individual. People have studied this over the years: They’ve looked at depression, libido, PMS [premenstrual syndrome], but nothing has ever come of it. It’s a very hard area to talk about. How do you define it?

In some animals, females experience estrus cycles during which they display physiological signals of their sexual receptiveness. Do these effects ever appear in humans, and could they be influenced by oral contraceptive use?

In some ways, how animals behave is more predictable than how humans behave. So there are more complex things going on. How we feel about people and what our libido is like arises from many, many factors. Some of it is hormonal, some of it is just energy level. Libido studies are exceedingly difficult to do. It’s not that they shouldn’t be done. But often the results show just small differences. Is that normal variation or is that a real effect? And a lot of these things get published. I think you always have to have a degree of skepticism. If there’s a consistent theme and it’s showing the same results, then you start to buy into it.

Let’s talk about other forms of contraception. In particular, IUDs [intrauterine devices] have been shown to be a safe and effective alternative. What would you tell a woman considering the pill versus an IUD?

It’s their decision. I say, do you want to take something every day that you immediately can stop when you don’t feel like taking it any more, or do you want something we can put in, and if you’re having any problems you can come back and see the doctor? People look at IUDs for long-term use. If you’re just using it for six months before you have another baby, you wouldn’t use an IUD, you’d use the pill.

Why isn’t there a male equivalent of the pill yet?

One of the challenges is, is it reversible? Clearly if you tie the tubes in a vasectomy, it’s very effective. But that’s not what most people want. Also, some of the candidate male contraceptive drugs [such as high-dose testosterone treatment] had side effects, and possibly even cardiovascular side effects. And they weren’t fully reversible. So some of those efforts fell by the wayside.

Do you think the main barriers to developing a pill for men have been societal or biological?

Biological. If someone said, ‘Here’s a pill you take for a month at a time,’ I think men would sign up readily. I can assure you that if pharmaceutical companies could develop such a drug, it would be a blockbuster, so they have a lot of interest in finding one. In reality, nothing’s there. It’s just the science hasn’t lent itself yet to any breakthrough that’s reversible, easy to use, etc. Part of the problem is you already have a very effective form of contraception. The question is, are male contraceptive methods going to be as widespread as the pill for women was when it was first introduced? The market’s saturated.

How do you see the role of the pharmaceutical industry in influencing studies?

There’s no question that companies will present their data in the most favorable light. You have to look at it carefully and at the investigators doing it. For the most part, any new drug is developed by pharmaceutical companies, with university researchers and others. You don’t have the money to do it independently. For me to do a randomized clinical trial of a new contraceptive compared to something else would be several million dollars, and no one’s willing to fund it.

People say you shouldn’t do anything with these companies. The problem is, the people who are the greatest experts are the people who develop these drugs. You learn who the better companies are, the ones that don’t overstate what they find. And people now have to declare their interests. Everyone’s biased, even the naysayers who say you shouldn’t do anything with a bias. It’s a gray area.

What are the pressing issues for contraception going forward?

The key is how you deal with the 50 percent unintended pregnancy rate. If we want to attack it, we’ll have to use more “long-acting reversible contraceptives” such as IUDs. I think contraception will be a significant issue in terms of dealing with excess population growth. It's a huge problem. Why do we have these global warming effects on Earth’s atmosphere? It’s because of the population.


Tanya Lewis, a graduate student in the Science Communication Program at UC Santa Cruz, earned her bachelor's degree in biomedical engineering at Brown University. At UCSC, she has worked as a reporting intern at the Stanford Medical School news office, the Santa Cruz Sentinel, and the SETI Institute's "Big Picture Science" radio program. This summer, she'll work as a science-writing intern at in San Francisco.

© 2012 Tanya Lewis