The synthetic hormones in birth control pills may affect mental health, research suggests.
- The combined hormonal contraceptive pill is the
second most popular form of contraception in the United States, besides
condoms.
- Ethinyl estradiol has been used in the
contraceptive pill since it was first created 60 years ago.
- Researchers have discovered that rats given this
hormone exhibited more behaviors associated with anxiety, compared to a
more natural estrogen used in a more modern form of the contraceptive
pill.
Rats given
synthetic estrogens used in birth control pills exhibited greater signs of
anxiety than those given natural estrogens, researchers have found.
The study
showed that synthetic estrogens were associated with higher sex hormone-binding
globulin and lower steroid hormone levels when compared to natural ones. The
researchers showcased their results at ENDO 2024, the Endocrine Society’s
annual meeting in
Boston, M.A., which was presented by a master’s student at Midwestern
University.
The
natural estrogen used in this study was similar to the one used in the
formulation for the NOMAC-E2 Combined Oral Contraceptive, known as Zoely, and
produced by the pharmaceutical company Merck. The synthetic estrogen used in
most combined hormonal contraceptive pills on the market is a highly potent
synthetic estrogen called ethinyl estradiol.
Researchers
had been looking for natural estrogen to use in combined hormonal contraceptive
pills since its inception 60 years ago, but these had not been potent enough
for those pills to be an effective form of hormonal contraceptive. This changed
in 2011 when Zoely was introduced to the market.
Abigail
Hegwood, M.S., a P.h.D. candidate who carried out the study, said she had
wanted to investigate the new, natural estrogen on the market as she had become
aware there was little epidemiological data on the side effects of specific
progestins and estrogens.
“Really I
wanted to know [whether there is] a difference between these two estrogens.
They just released this natural estrogen on the market. Does this possibly give
us an opportunity to find a difference between formulations in terms of
behavioral side effects?” she said.
She now
plans on submitting the results of this research for peer review in the coming
months.
Different
behavior with synthetic estrogen
Three
groups of 12 female rats were given either ethinyl estradiol a synthetic
estrogen with dienogest, a progestin often combined with it in oral combined
hormonal contraception, or estradiol valerate a natural estrogen with
dienogest, or a control, delivered via a subcutaneous pump for 28 days. The
researchers tested the rats’ spatial awareness and anxiety in a maze test,
between days 20-28, and collected serum samples on day 28.
The
researchers discovered that the rats had similar spatial memory across all
three groups. However, those who were given the synthetic estrogen had a
different response to the spatial memory task in the maze test, which is
believed to be associated with anxiety-like behaviors in rats.
Serum
samples also showed that both types of estrogen reduced circulating
testosterone.
The
authors note levels of the type of estradiol made in the ovaries were below the
detection limit in over half of rats given ethinyl estradiol.
How
estrogen is linked to spatial memory and anxiety
Previous
research has shown that higher levels of testosterone and E2 reduce
anxiety-related behaviors and improve spatial memory, authors noted. They
propose that the results they have seen are due to the effect of synthetic
estrogens on the brain.
“Ethinyl
estradiol and estradiol valerate have different effects on hormone-binding
globulin. And hormone-binding globulin can bind and render steroid hormones in
the blood unavailable for use by the body. And so we know that ethinyl estradiol
increases hormone-binding globulin, which increases the amount of bound steroid
hormone in the blood,” said Hegwood.
“So my
hypothesis would be that because ethinyl estradiol is having this greater
effect on the availability of steroid hormones, it would have a greater effect
on the actions that these steroid hormones have on the body, including the
brain,” she added.
Her
supervisor Alesia Prakapenka, Ph.D., an assistant professor in the
Biomedical Sciences program at Midwestern University in Downers Grove, Ill,
told Medical News Today:
“Another
potential outcome is there’s the feedback loop that’s being halted by the
contraceptive treatments between the hypothalamus, the pituitary, and the
gonads.”
Naturally-produced
circulating estrogen was below the level of detection in many of the rats given
ethinyl estradiol.
“What we
actually saw is that with the synthetic ethinyl estradiol group, more than half
of the samples in that group had 17-beta estradiol levels that were actually
below the limit of detection. And so it could be that even if it’s not the
hormone itself from the contraceptive, it may be changing something within the
feedback loop that then could be having that effect,” explained Prakapenka.
Prakapenka
said there hasn’t been much focus on the behavioral effects of hormonal
contraception.
“I think
bringing this to attention is exciting because now we can start to look at it
more and then combine it with additional factors that are across the lifespan
could be impacting females, including pregnancy, including menopause,” she
said.
TAILORED
BIRTH CONTROL OPTIONS
“There’s a lot of development that’s happening with different
options for menopausal hormone therapy. So maybe taking those strategies,
applying them to contraceptive use as well, kind of across the board, what a
female can go through and how we can inform them of this. These are your
options. These are kind of the individual changes that you may experience and
how to adjust based on that individual woman, as opposed to women as a whole or
females as a whole.”— Alesia Prakapenka, Ph.D.
How
hormonal contraception affects behavior
While it
was possible that combined hormonal contraception could have an effect on the
brain and therefore behavior, it was likely that this effect would be small,
said Professor Jonathan
Schaffir, MD, and Vice
Chair of Education in the Department of Obstetrics and Gynecology at the Ohio
State University College of Medicine, who was not involved in the research.
“There are
receptors for estrogens as well as other steroids in the human brain, and that,
you know, we know that providing exogenous hormones can influence mood and
behavior to some degree. That said, I think that the influence of oral
contraceptives is usually small and it’s a small percentage of women who have
any significant side effects that affect mood,” he told Medical News
Today in an interview.
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