Oral contraceptive hormone doses could be reduced by over 90%
Research shows that it is possible to reduce the total dose by 92% in estrogen monotherapy, 43% in progesterone monotherapy,
A research article published in the journal PLOS (Public Library of Science) Computational Biology demonstrates that the amount of hormones in oral contraceptives can be dramatically reduced without sacrificing efficacy.
Anovulation, the purpose of oral contraceptives
Anovulation, the absence of ovum production to cancel fertilization, is the biological intent of hormonal contraception.
“Anovulation refers to a menstrual cycle characterized by the absence of ovulation. Exogenous hormones such as synthetic progesterone and estrogen 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 utilizes optimal control theory on a modified menstrual cycle model to determine the minimum total exogenous estrogen/progesterone dose, and timing of administration to induce anovulation.”
How oral contraceptives work
The normal menstrual cycle:
The figure shows the transition of a follicle, from its growth in the follicular phase to its rupture during ovulation, as well as its transformation to a corpus luteum and degradation in the luteal phase. The blue arrow indicates the control of the hypothalamus in the secretion of pituitary hormones. The black arrows represent the influence of the pituitary system on the ovarian system through FSH and LH, and the orange arrows show the response of the ovarian system through E2, P4, and Inh.
Pituitary and ovarian hormone levels in a normal menstrual cycle. The hormones LH, FSH, and E2 peak in the late follicular phase while P4 and Inh reach maximum value in the luteal phase.
Hormonal contraceptives, composed of progesterone alone or a combination of estrogen and progesterone, induce anovulation by preventing the mid-cycle rise in LH (luteinizing hormone) secretion. The exogenous progesterone suppresses follicular development and gonadotropin (the pituitary hormones FSH and LH) secretion causing an insufficiency of FSH (follicle stimulating hormone) that prevents follicle growth. The lack of follicle growth results in too little estradiol production to trigger the normal surge of LH. The estrogen component of oral contraceptives further suppresses FSH secretion and the generation of a follicle, stabilizing the endometrium to minimize bleeding.
Achieving the optimal dose of oral contraceptives
For the first time, the authors have used sophisticated analytical methods to advance the safety and efficiency or OCs by applying a menstrual cycle model which correctly predicts the pituitary and ovarian levels throughout a normal cycle and shows the decrease in maximum hormone levels caused by oral estrogen and/or progesterone.
“To our knowledge there has been no study applying optimal control theory on the menstrual cycle model. Optimal control could provide drug administration scheme which greatly enhances contraception outcome by significantly minimizing risks associated with high doses such as venous thromboembolism and myocardial infarction [3, 30–32].”
The authors summarize their findings:
Our study presents an improved mathematical model for hormonal control of the menstrual cycle and applies optimal control theory to minimize total exogenous estrogen and/or progesterone dose, and determine timing of administration that lead to contraception. We observe a reduction in dosage of about 92% in estrogen monotherapy and 43% in progesterone monotherapy. Our simulations show that it is most effective to deliver the estrogen contraceptive in the mid follicular phase. In addition, we illustrate that combination therapy significantly lower doses further. Our findings may give clinicians insights into optimal dosing scheme for contraception.
See also an interview of the research team that produced this study in Technology Networks.
