Oral Contraception: Beyond What Meets the Eye. Sorry, the Ovaries!

Keywords
Contraception; Oral contraceptives; Cardiovascular risk

The concept of oral contraception, historically, was supposed to enable control of unwanted pregnancies and facilitate family planning for women of reproductive age in an elegant fashion for everyone needing it. However, the influence of different prescriptions on women’s health during active use, as well as later on in life – beyond the quintessential fear of thromboses lay women worldwide have – has not been studied extensively or meticulously, despite the widespread use. Also, with some countries recently starting to embrace the over-the-counter concept for oral contraceptives in addition to the mechanical ones, a mandatory visit to a physician to get a personalized prescription will become a growing phenomenon and its public health consequences are unforeseeable, evidently.

In the current issue of IJCS, we had the pleasure of reading a paper by Gomes et al,¹ who presented their original article with results of a cross-over study of the influence of high-intensity interval training (HIIT) on the lipid and inflammatory profile of women using combined oral contraceptives (COC) that showed a beneficial effect to the latter, but not the former.

For the purpose of this Editorial, the Authors conducted an extensive systematic review of the currently available evidence hoping to identify gaps in the current knowledge globally.

Besides, dedicated societies – such as the American College of Obstetricians and Gynecologist²-⁵ and the European Board and College of Obstetrics and Gynecology⁶ – an occasional comment on importance of contraception can be found in cardiovascular societies’ guidelines or position papers offering advice on long-term management of women with heart disease, but with no particular detailed, yet comprehensive, “Dos” and “Don’ts” being currently available. Therefore, aiming to facilitate further choices for all facing one , we have tried to summarize contraindications and cautious use in Figure 1. As pictured, the two prescription options – combined estrogen-progestin oral contraceptives in monophasic and biphasic version and progestin-only oral contraceptives – are globally available; however, how a woman and her physician(s) choose the best one considering the indication (contraception or other) remains in the domain of personalized medicine.

Figure 1
Oral contraceptives’ formulations.

The pro-inflammatory, endothelial-dysfunction promoting and pro-thrombotic effects cause a myriad of pro-atherothrombotic states that facilitate cerebrovascular and cardiovascular events accompanied by diabetes and dyslipidemia, especially in the presence of pre-existing smoking.

Pasvol et al⁷ have observed an increase in the risk of inflammatory bowel disease in women using combined, instead of progestogen-only, pills in a UK cohort of patients, consistent with Quinn et al⁸ that reported that women using oral contraceptives to have higher oxidative stress and CRP.

Jimoh et al,⁹ in the African population, have shown lipid profile alterations for COC, it is quite the opposite for progestin-only oral contraceptives in a Spanish cohort¹⁰ that left glucose, insulin, and hemostasis intact. Short-term cardiovascular risk gets aggravated with COC;⁹ however, the WISE cohort¹¹ unadjusted prior oral contraceptives’ use was associated with lower longer-term all-cause and cardiovascular disease mortality, except for women with very elevated menopausal systolic blood pressure. Still, none of these cohorts reported the percentage of women with family hypercholesterolemia, whose issue of oral contraceptive choice remains a debate.¹²

Lamenting on the regrettable outcomes will surely not improve healthcare for women worldwide who need it despite their respective countries’ economies and social determinants of health,¹³,¹⁴ yet region- and country-specific solutions¹⁵ must be implemented if we aim to improve cardiovascular and reproductive care of women on a global scale.

However, when the Venn diagram of “the pill” as an over-the-counter medication⁴ overlaps with a rising hostility to abortion rights for women worldwide – although it risks opening the dangerous doors of clandestine abortions we had hoped to have closed forever in the previous century – we find ourselves in the area of the only viable and sustainable solution for both our patients and ourselves and that is a more comprehensive, global, and ethnically diverse research agenda that mimics the population we see in our hospital corridors and clinics’ waiting rooms to mitigate the side effects of existing therapies and progress to new ones.

• Editorial referring to the article: Effects of Physical Exercise on Lipid and Inflammatory Profile of Women Using Combined Oral Contraceptive: A Cross-Over Study

References

• ¹
  Gomes VA, Sacramento MS, Cecilia LMS, Jesus DS, Barbosa JS, Almeida FOB, et al. Effects of Physical Exercise on Lipid and Inflammatory Profile of Women Using Combined Oral Contraceptive: A Cross-Over Study. Int. J. Cardiovasc. Sci. 2022;35(4),500-510. doi: 10.36660/ijcs.20200399.
  » https://doi.org/10.36660/ijcs.20200399
• ²
  ACOG Practice Bulletin No. 206: Use of Hormonal Contraception in Women With Coexisting Medical Conditions. Obstet Gynecol. 2019;133(2):128-50. doi: 10.1097/AOG.0000000000003072.
  » https://doi.org/10.1097/AOG.0000000000003072
• ³
  American College of Obstetricians and Gynecologists’ Committee on Adolescent Health Care. Gynecologic Considerations for Adolescents and Young Women With Cardiac Conditions: ACOG Committee Opinion, Number 813. Obstet Gynecol. 2020;136(5):90-9. doi: 10.1097/AOG.0000000000004133.
  » https://doi.org/10.1097/AOG.0000000000004133
• ⁴
  Over-the-Counter Access to Hormonal Contraception: ACOG Committee Opinion Summary, Number 788. Obstet Gynecol. 2019;134(4):886-7. doi: 10.1097/AOG.0000000000003474.
  » https://doi.org/10.1097/AOG.0000000000003474
• ⁵
  Steenland MW, Rodriguez MI, Cohen JL. Changes in the Supply Duration of Combined Oral Contraception During the Coronavirus Disease 2019 (COVID-19) Pandemic. Obstet Gynecol. 2022;139(3):455-7. doi: 10.1097/AOG.0000000000004685.
  » https://doi.org/10.1097/AOG.0000000000004685
• ⁶
  Mahmood T, Bitzer J, Nizard J, Short M. The Sexual Reproductive Health of Women: Unfinished Business in the Eastern Europe and Central Asia Region. Eur J Obstet Gynecol Reprod Biol. 2020;247:246-53. doi: 10.1016/j.ejogrb.2019.12.038.
  » https://doi.org/10.1016/j.ejogrb.2019.12.038
• ⁷
  Pasvol TJ, Bloom S, Segal AW, Rait G, Horsfall L. Use of Contraceptives and Risk of Inflammatory Bowel Disease: A Nested Case-control Study. Aliment Pharmacol Ther. 2022;55(3):318-26. doi: 10.1111/apt.16647.
  » https://doi.org/10.1111/apt.16647
• ⁸
  Quinn KM, Cox AJ, Roberts L, Pennell EN, McKeating DR, Fisher JJ, et al. Temporal Changes in Blood Oxidative Stress Biomarkers Across the Menstrual Cycle and with Oral Contraceptive Use in Active Women. Eur J Appl Physiol. 2021;121(9):2607-20. doi: 10.1007/s00421-021-04734-0.
  » https://doi.org/10.1007/s00421-021-04734-0
• ⁹
  Jimoh OS, Abdul IF, Balogun OR, Biliaminu SA, Adeniran AS, Jimoh-Abdulghaffaar HO, et al. Atherogenic and Cardiovascular Risks of Women on Combined Oral Contraceptives: A Comparative Study. Niger J Clin Pract. 2021;24(12):1759-65. doi: 10.4103/njcp.njcp_431_20.
  » https://doi.org/10.4103/njcp.njcp_431_20
• ¹⁰
  Palacios S, Colli E, Regidor PA. Metabolic and Laboratory Effects of a Progestin-only Pill Containing Drospirenone 4 mg in Comparison to Desogestrel 75 µg: a Double-blind, Double-dummy, Prospective, Randomised Study. Eur J Contracept Reprod Health Care. 2021;26(6):454-61. doi: 10.1080/13625187.2021.1957094.
  » https://doi.org/10.1080/13625187.2021.1957094
• ¹¹
  Barsky L, Shufelt C, Lauzon M, Johnson BD, Berga SL, Braunstein G, et al. Prior Oral Contraceptive Use and Longer Term Mortality Outcomes in Women with Suspected Ischemic Heart Disease. J Womens Health (Larchmt). 2021;30(3):377-84. doi: 10.1089/jwh.2020.8743.
  » https://doi.org/10.1089/jwh.2020.8743
• ¹²
  Balla S, Ekpo EP, Wilemon KA, Knowles JW, Rodriguez F. Women Living with Familial Hypercholesterolemia: Challenges and Considerations Surrounding Their Care. Curr Atheroscler Rep. 2020;22(10):60. doi: 10.1007/s11883-020-00881-5.
  » https://doi.org/10.1007/s11883-020-00881-5
• ¹³
  Behboudi-Gandevani S, Ramezani Tehrani F, Cheraghi L, Noroozzadeh M, Farahmand M, Azizi F. Trends of Contraception Use Among Married Reproductive Age Women: Tehran Lipid and Glucose Cohort Study 2002-2011. Sex Reprod Healthc. 2017;12:116-22. doi: 10.1016/j.srhc.2017.04.003.
  » https://doi.org/10.1016/j.srhc.2017.04.003
• ¹⁴
  Bond RM, Gaither K, Nasser SA, Albert MA, Ferdinand KC, Njoroge JN, et al. Working Agenda for Black Mothers: A Position Paper From the Association of Black Cardiologists on Solutions to Improving Black Maternal Health. Circ Cardiovasc Qual Outcomes. 2021;14(2):e007643. doi: 10.1161/CIRCOUTCOMES.120.007643.
  » https://doi.org/10.1161/CIRCOUTCOMES.120.007643
• ¹⁵
  Parapid B, Kanjuh V, Kostić V, Polovina S, Dinić M, Lončar Z, et al. Women’s Health in Serbia - Past, Present, and Future. Srpski Arhiv za Celokupno Lekarstvo. 2021;149(11):745-54. doi: 10.2298/SARH211208105P.
  » https://doi.org/10.2298/SARH211208105P

Publication Dates

• Publication in this collection
  13 July 2022
• Date of issue
  2022