A new study suggests that the hormone dosage in common contraceptives could be drastically reduced while still being effective in preventing ovulation.
The scientists who carried out the study believe their findings could provide new insight into the complexities of the endocrine system and support the need for more precise and individualized hormonal contraception, a move that could benefit many people.
Mathematician Brenda Lyn A. Gavina from the University of the Philippines Diliman and colleagues from the Philippines, Korea, the US, and Denmark constructed mathematical computer models to explore the optimal timing and dosing of hormonal contraceptives to see if dosages – and, therefore, potential side effects – could be reduced.
The endocrine system regulates and influences the progression of a human menstrual cycle at multiple stages by secreting hormones from the hypothalamus, pituitary gland, and ovaries.
To learn more about the interactions of these hormones, Gavina and her team collected information on pituitary and ovarian hormone levels from 23 healthy women between the ages of 20 and 34, who all reported regular menstrual cycles that lasted between 25 and 35 days and had shown evidence of ovulation in their most recent cycle.
The researchers used this real-life data to create a mathematical model of the normal menstrual cycle, enabling them to predict daily levels of hormones during a normal menstrual cycle and explore the effects of the administration of exogenous hormones on these levels.
The most common birth control methods – pills, injectables, and implants – introduce one or both of the synthetic hormones estrogen and progesterone to the bloodstream to prevent pregnancy.
Synthetic hormonal contraceptives work to block ovulation, prevent egg release and fertilization, and change the cervical mucus to hinder sperm and prevent egg implantation.
The modeling was able to make predictions about not only the minimal dose of these hormones needed to achieve contraception but also the effects of combining estrogen and progesterone and the optimal timing of the doses.
"Numerous previous modeling studies have examined the menstrual cycle, how it is formed, and how it can be altered," the authors write in their published paper.
"To our knowledge, our work is the first to use modeling to study timing of dosing, thereby minimizing the dose even more."
The method used in the modeling, known as optimal control theory, is certainly not new. Past research has used it to show how treatment protocols in diabetes and prostate cancer could be optimized and, according to the study authors, to describe optimal hormone dosing for in vitro fertilization (IVF).
Now the team thinks the same approach could be used to help optimize doses of hormonal contraceptives. However, they note that their model doesn't account for variation in cycle length, which varies within and between people.
The modeling suggests that birth control pills could work effectively with far lower doses of estrogen or progesterone than those currently prescribed and that taking hormones at specific times during the menstrual cycle can be more effective than taking them constantly.
"Results show that it is possible to reduce the total dose by 92 percent in estrogen monotherapy, 43 percent in progesterone monotherapy," the team writes, "and that it is most effective to deliver the estrogen contraceptive in the mid follicular phase."
And when both hormones are taken in combination, they found that even lower doses of each hormone could be sufficient to prevent pregnancy.
"Finally, we show that by combining estrogen and progesterone, the dose can be lowered even more," the team adds.
Ovulation suppression is helpful for more than just birth control; it can help ease unpleasant, distressing, and sometimes downright painful menstrual symptoms and, perhaps surprisingly, lessen the risk of injury to the anterior cruciate ligament (ACL).
Even though we've used hormonal contraceptives for decades, the full effects are still poorly understood.
"Despite many benefits," Gavina and team write, "adverse side effects associated with high doses, such as thrombosis and myocardial infarction, cause hesitation to usage."
Of course, it would be ideal if everyone shared the responsibility of contraception equally, and we are exploring solutions, including further non-hormonal avenues, though they are proving to be complex.
"Results from this study have potential to provide contraception to more women," the researchers say, "in particular since lower doses also decrease the risks for adverse side effects".
While this work remains a modeling exercise for now, it highlights the benefits of ongoing research to improve commonly used contraceptives.
The peer-reviewed study has been published in PLOS Computational Biology.