Does the Pill really cause weight gain?

“Scientists have scotched the notion that taking the contraceptive pill can make women fatter,” the Daily Express has reported.

This news story relates to research that looked at weight changes in 10 obese or normal weight macaque monkeys that were given the combined oral contraceptive pill for eight months. The study found that obese monkeys lost both fat and weight while being treated with the Pill. However, this was a small animal study and the research did not feature a test group of monkeys that did not receive the Pill, therefore it is not possible to say for certain whether the weight loss in the monkeys was due to the Pill.

There have already been robust randomised controlled trials of the effects of combination contraceptives in humans, so it is surprising that these US authors felt the need to develop a primate model. For example, a systematic review of human studies conducted in 2008 agrees with the broad conclusions made in this study. That said, despite being an animal study this research does add further support to a body of medical data that suggests there is insufficient evidence to claim that the Pill causes weight gain.

Where did the story come from?

The study was carried out by researchers from Oregon Health and Science University, Portland USA and was funded by the Society of Family Planning. The study was published in the peer-reviewed medical journal, Human Reproduction.

The_ Metro_ did not highlight the small size of this primate study and over-emphasised the relevance to humans. The Daily Express concluded its piece well by saying that the study “may not resolve the debate as it was only a handful of monkeys. Far larger studies in humans are needed to provide accurate data”.

What kind of research was this?

This was an animal study that looked at whether taking the contraceptive pill was associated with weight gain in female monkeys. The researchers were interested in this as they say that retaining weight is a common complaint amongst women taking oral contraceptives, reportedly being raised by between 30%-75% of users. This complaint is thought to be the main reason for women to stop taking them.

However, the researchers say that a recent systematic review of 42 randomised controlled trials that had looked at whether the Pill affected weight did not find sufficient evidence to suggest that it did. The researchers point out that this systematic review did not include any studies featuring obese women, therefore it may not represent the whole population. They support this argument by citing data from the World Health Organisation that suggests that approximately 30% of the US population is obese.

The researchers chose to do an animal study (rather than one following and comparing women who were taking or not taking the Pill) because they said it would be difficult to control how much women ate and how active they were over the long term. They say that monkeys have a similar reproductive system to humans, alongside similar metabolism and food intake.

What did the research involve?

The researchers used two groups of adult female monkeys. Five of the monkeys had a normal body mass index. The body mass index for these monkeys was calculated in the same way it would be in humans, by dividing mass (in kilograms) by height in metres squared. In the monkeys the normal BMI group had a BMI of between 22.5 and 27.3. Five of the monkeys were obese, with a BMI of  between 32.5 and 35.1. The monkeys in this group were inherently obese and had not been made so for the purposes of the study. For humans, the cut-offs for BMI are 20-25 for optimal weight, 25-30 overweight and over 30 for obese.

The monkeys underwent a three-month baseline monitoring period, received the oral contraceptive for the next eight months and finally had a three-month post-treatment period. They used a combination pill, which was given every day for eight months without placebo day breaks (which means they did not include any inactive pills that are sometimes used in human contraceptives courses to maintain menstruation). The monkeys were given a dose equivalent to the dose a woman would take, but adjusted for their size.

The monkeys were given the equivalent number of calories to each other (based on their individual BMI) every day. The researchers measured the weight, percentage body fat, metabolic rate, blood sugar and enzymes in the blood that regulate sugar levels, appetite and metabolism. The researchers also measured the monkeys’ activity by fitting them with a special collar that measured how much they moved around.

What were the basic results?

The researchers found that all the animals displayed a decrease in weight between the start of the study (known as the baseline) and the end of the eight months on the Pill. However, they found that when they analysed the data from the obese animals and normal-weight animals separately only the obese animals showed a significant decrease in body weight (they lost 8.58% of their weight compared to baseline). The normal BMI group had a smaller decline, which was not statistically significant.

The researchers then looked specifically at fat loss, rather than loss of overall weight. The obese group showed a decrease in body fat from baseline to the end of the eight-month period on the Pill, which was not seen in the normal BMI group. The researchers found that at the end of the three-month post-treatment period the monkeys returned to the same body fat levels they had prior to the Pill. They found that there was no change in lean body mass in any of the monkeys.

There were no differences in the food intake or activity levels of the monkeys over the course of the study.

Pill-use was found to increase metabolic rate at night (the basal metabolic rate) in both the obese and normal weight monkeys. This returned to baseline levels in the post–treatment period.

At baseline there were no differences in the concentration of blood sugar in the obese monkeys compared to the normal weight monkeys but the levels of insulin (which regulates blood sugar) and leptin (which regulates appetite and metabolism) were higher in the obese group. During the period of taking the Pill, the obese group’s blood sugar levels were significantly lowered, as were leptin levels. Leptin levels continued to be low after treatment with the Pill had been stopped. Insulin levels were increased in the normal BMI group while they were taking the Pill.

How did the researchers interpret the results?

The researchers say that combined oral contraceptives “increase basal metabolic rate and result in weight loss due to a reduction of body fat but not lean body mass in obese female macaques (monkeys) maintained on a stable diet”. They also highlight that none of the animals on oral contraceptives showed weight gain.

The authors suggested that the oestrogen contained within the Pill may increase metabolic rate and loss of body weight in obese monkeys during oral contraceptive use. They said that their study argues against discontinuation of oral contraceptives for weight loss purposes, a practice that they say places women at risk of unplanned pregnancies.

Conclusion

This small animal study showed that obese monkeys receiving the oral contraceptive pill continuously for eight months lost a small amount of weight. The researchers had used monkeys for this research so they could control the amount of food the monkeys ate and monitor their activity, something that would not be feasible in a long-term human study. This may not reflect normal human eating behaviour, where different women may choose different types of food with differing amounts of calories, which could potentially be affected by how they are feeling and their hormone levels.

A limitation with the study was that there were no control animals (animals not receiving the Pill). It is therefore not possible to say whether the weight loss was due to the Pill or the diet and housing conditions that the animals were kept in over the course of the study. However, the observation that body fat returned to baseline levels in the obese animals after they stopped taking the Pill suggests that it may have some effect on the fat metabolism.

Additionally, the monkeys were given the Pill continuously for eight months. For most contraceptive pills, women take placebo pills or have a break of seven days before starting the next packet, to allow for their menstrual bleed. Although active pills can occasionally be taken continuously it is not recommended that women take the pill in this manner for as long as eight months.

This was animal research, and featured a number of limitations. It would be preferable to look at conclusions drawn from high-quality research in humans, such as past and ongoing clinical trials.