Researchers believe that lowering hormone levels for contraception can still be effective at preventing ovulation, with computer modelling results showing they could reduce hormones in oestrogen-only contraceptives by as much as 92% and still block ovulation.
Hormonal contraceptives are a popular option for preventing pregnancy, but can sometimes cause side effects – the catalyst for the researchers to determine whether it was possible to both lower the hormone dosage in contraceptives and the administration timing while retaining their effectiveness.
The team of scientists from the University of the Philippines Diliman say their study, which was published in the journal PLOS Computational Biology, suggests that it is, indeed, possible to reduce hormones in both oestrogen-only and progesterone-only contraceptives by a significant degree and still prevent ovulation, reports Medical News Today.
How hormonal contraceptives work
The Centres for Disease Control and Prevention (CDC) said in the US, 12.6% of females aged 15 to 49 use an oral contraceptive, with 10.3% using long-acting reversible contraceptives.
Hormonal contraceptive devices work by using synthetic hormones like oestrogen and progesterone to prevent pregnancy, and work in multiple ways, including stopping ovulation or causing the uterine lining to thin so that an implanted egg cannot attach.
Doctors will also sometimes prescribe them for polycystic ovary syndrome (PCOS) to reduce the size of cysts and thereby reduce pain, or in the treatment of endometriosis, to help control pain and excessive bleeding.
Hormonal contraceptives’ side effects vary from mild to severe, and can include nausea, headaches, stroke, blood clots, hypertension and abdominal cramping.
Also, smokers on taking hormonal contraceptives have more risk of deep vein thromboembolism.
The researchers wanted to expand on previous contraceptive research, and analyse whether lower hormone doses could still be effective in preventing pregnancy.
Not only did they consider reducing the amount of hormones in the contraceptives, but they also theorised that it is possible to adjust the timing of different dosages to receive maximum benefit.
They studied data from 23 females aged 20 to 34, who had regular menstrual cycles that lasted from 25 to 35 days.
They ran their data on two models: the pituitary model and the ovarian model.
The pituitary gland is part of the endocrine system that regulates hormones which affect ovulation. With the pituitary model, they analysed the timing of the release of ovulation hormones as well as the hormone levels.
With the ovarian computer model, the scientists looked at how the ovaries responded to the hormones released.
Additionally, they ran models to see how different levels of oestrogen and progesterone affected the menstrual cycle.
Hormone level reduction possible
Their computer models showed it is possible to adjust the hormone dosage and prevent ovulation. Not only did the models show that hormones could be reduced, but the researchers also found it is possible to focus on adjusting the dose during certain parts of the cycle and still have the contraceptives be effective.
With oestrogen-only contraceptives, the scientists reduced the dosage by 92% and retained effectiveness. In progesterone-only contraceptives, they reduced the dose by 43% and still had contraceptive benefits.
As far as the timing of the hormone delivery goes, the authors said “it is most effective to deliver the oestrogen contraceptive in the mid-follicular phase”.
Study author Brenda Gavina, a doctoral researcher at the University of the Philippines Diliman, said: “It was surprising that theoretically, our mathematical model – with the simplifying assumptions – showed that as low as 10% of the total exogenous oestrogen dose in constant administration could achieve contraception, as long as this dosage is perfectly timed.
“Lower doses reduce risks of adverse side effects like thrombosis and myocardial infarction associated with large doses,” she noted.
“The current mathematical model does not capture all factors in contraception since the reproductive function in women is a very complex, multiscale dynamical system,” she said, adding that as more data come out, “it can be refined to address other contraception issues.”
While the results show that adjusting the hormone dose in contraceptives is possible while maintaining efficacy, the study is not at the point of having clinical use yet, said some experts.
Dr Sandra Hurtado, assistant professor of obstetrics, gynaecology and reproductive sciences at McGovern Medical School at UTHealth Houston, who was not involved in the study, said the mathematical model needs to “undergo testing in an animal model and in humans to be able to test its safety and efficacy”.
However, she did see potential in the study. “If there were a way to test and record the hormone levels in each individual and be able to give that person the dose at the correct time, that would be ideal.”
She added that taking this research further, developing something like an automated insulin delivery system, could be helpful. “Those are costly and not justifiable for contraceptive use, but with continued advancing technology and decrease in cost of electronics, hopefully, it can be developed in the near future.”
Study details
Toward an optimal contraception dosing strategy
Brenda Gavina, Aurelio de los Reyes, Mette Olufsen, Suzanne Lenhart, Johnny Ottesen.
Published in PLOS Computational Biology on 13 April 2023
Abstract
Anovulation refers to a menstrual cycle characterised by the absence of ovulation. Exogenous hormones such as synthetic progesterone and oestrogen have been used to attain this state to achieve contraception. However, large doses are associated with adverse effects such as increased risk for thrombosis and myocardial infarction. This study utilises optimal control theory on a modified menstrual cycle model to determine the minimum total exogenous oestrogen/progesterone dose, and timing of administration to induce anovulation.
The mathematical model correctly predicts the mean daily levels of pituitary hormones LH and FSH, and ovarian hormones E2, P4, and Inh throughout a normal menstrual cycle and reflects the reduction in these hormone levels caused by exogenous oestrogen and/or progesterone. Results show that it is possible to reduce the total dose by 92% in oestrogen monotherapy, 43% in progesterone monotherapy, and that it is most effective to deliver the oestrogen contraceptive in the mid follicular phase.
Finally, we show that by combining oestrogen and progesterone the dose can be lowered even more. These results may give clinicians insights into optimal formulations and schedule of therapy that can suppress ovulation.
PLOS Computational Biology article – Toward an optimal contraception dosing strategy (Open access)
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