The Mechanisms of the Oral Contraceptive Pill

The monophasic oral contraceptive pill (OCP) is one of the most effective contraceptive methods and is termed a combination pill as it contains both progestin and oestrogen (Sullivan, 2017). The monophasic OCP’s aim to prevent unplanned pregnancy as well as provide other therapeutic actions. Interactions involve antibiotics, certain nutrients and the herb St. John’s Wort.
 
The hormones within the monophasic combined oral contraceptive (COC’s), progestin and oestrogen, work to subdue ovulation, thicken cervical mucus, and thin the lining of the uterus creating an environment that halts sperm from travelling up the female reproductive system and implanting (Cooper et al, 2019). The reduction of the secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) occurs via the progesterone negative feedback loop within the hypothalamus to reduce the pulse frequency of gonadotropin-releasing hormone (GnRH) (Cooper et al, 2015). This halts the mid-cycle LH surge as well as the development of the follicle, preventing ovulation. Oestrogen also plays a role in inhibiting follicular development as it acts to slow FSH via its negative feedback on the anterior pituitary. However, its role is not as prominent as progesterone in stopping ovulation.

Therapeutic uses of taking monophasic OCP’s apart from contraception include regulation of the cycle for those with polycystic ovarian syndrome and premenstrual syndrome (ESHRE, 2005). When taken in uninterrupted regiments, COC’s have proven to reduce the overall volume and duration of painful bleeds. Those who suffer from extreme bleeding have experienced noteworthy declines of 50% less menstrual blood loss and shorter time frames of bleeding (Dragoman, 2014). Women who experience anovulatory bleeds (e.g. those with obesity or polycystic ovary syndrome), improve with the use of COC’s. Additionally, continuous dosing of COC’s lowers a woman’s lifetime risk of developing endometrial (50% reduction), ovarian and colorectal cancer. Other conditions improved by COC’s include acne, PMS and hirsutism (unwanted hair growth) due to reducing surplus male hormone androgen exposure and increasing levels of sex hormone globulin (Dragoman, 2014).
 
Combined OCP’s are formulated with equal amounts of oestrogen and progesterone taken orally at the same time every day for optimal efficacy and to prevent ‘breakthrough’ bleeds (Endeavour College of Natural Health, 2019). Combined OCP’s are administered in 28-day prescriptions, that contain 7 placebo pills and 21 active hormone pills. An inactive placebo pill is taken during cycle days 21-28, the lack of the active hormonal pills trigger a withdrawal bleed. Extended monophasic regimes are used by many women to delay withdrawal bleeding where the inactive pill-taking is skipped and hormonal pills are continued (Stewart et al, 2015). Women can begin taking the pill at any point in their menstrual cycle, ensuring adherence to a regime of 24-hour dosages to reduce adverse effects and full efficacy. Within the first 7 days, monophasic OCP’s are not entirely effective in avoiding pregnancy, thus other forms of contraception should be used to ensure protection (e.g. condoms). If one day is missed, then the missed pill should be taken immediately and the regular 24-hour interval should be resumed (Cooper et al, 2019).
 
A multitude of adverse effects may come with taking COC’s making them unsuitable for some women. Adverse reactions include nausea, breast tenderness, bloating and fluid retention, decreased libido and some breakthrough bleeding (Dragoman, 2015). Breakthrough bleeds that may occur are usually short term and aren’t harmful. Woman with a strong history of migraines may have an initial rise in the incidence of attacks. However, individuals with hormonally fluctuating migraines may notice progress in the incidence due to uniformed levels throughout their cycle (Stoppler, 2019). The risk of developing arterial venous thromboembolism is very rare but increases threefold for women on OCP’s, resulting in obstruction of blood vessels by clots (de Bastos, 2014). The jeopardy increases in women who smoke, have BMI’s at either end of the scale and is contraindicated in women who have had a personal or familial history with the disease (Dragoman, 2015). The risk appears to be the highest within the first year of exposure to COC’s and reduces after a prolonged duration.
 
Women should always consult with their physician when choosing contraceptive methods to ensure that the correct type of OCP is chosen as well as understanding the potential effects and alternatives. During pregnancy and lactation monophasic OCP’s are not recommended for the foetal health and cause a decline of volume of breast milk. Further contraindications involve women who have uncontrolled hypertension and those with diabetes as they may undergo some hyperglycaemic reactions. However, these issues can be addressed by changing the type of pill and managing the condition with the support of a clinician. Women who are over the age of 35 years and smoke are contraindicated in the use of COC’s as it may affect their cardiovascular health and create symptoms of deep vein thromboembolism. Further conditions include those with reproductive cancers and heart disease due to the high-risk nature of these health issues (Cooper et al, 2019).
 
Normal physiology of the menstrual cycle involves the release of hormones from the hypothalamus with GnRH encouraging the discharge of LH and FSH from the anterior pituitary, then signalling the sloughing off endometrial cells from the uterine wall followed by bleeding. Oestrogen and progesterone are released from the ovaries and a mature oocyte is released followed by ovulation (Tortora et al, 2018). Diagram two highlights the fluctuation of reproductive hormones during a regular menstrual cycle. The action of COC’s, as seen in diagram 3, stop regular menstrual cycles by suppressing the ability of hormones including FSH and LH to be released thus halting ovulation and oocyte fertilisation. Without the influences of FSH and LH hormones the growth of ovarian follicles fragments resulting in minimal oestrogen levels. Subsequently, ovarian hormones needed to support insemination are subdued and unplanned pregnancy is avoided (Knudtson, 2019).
 
Drug interactions with OCP’s can lead to the failure of the efficacy and result in an unplanned pregnancy. The concomitant use of drugs that have microsomal enzyme-inducing activity reduces the ability of COC’s to work, such as antibiotics (e.g. tetracycline and rifampin) (D’Arcy, 1986). Rifampin has been proven to reduce serum oestrogen concentrations by increasing the breaking down of OCP’s and excretion via the bile into faecal matter, thus reducing the ability of OCP’s to prevent ovulation (Zhanel et al, 1999). Further, the interactions with the herbal medicine St. John’s Wort has been proven to reduce the ability of OCP’s due to the hypericin content. The herbal medicine is an inducer of CYP384 as well as P-glycoprotein which changes the pharmacodynamics of COC’s, meaning that the effectiveness of the drug is diminished. The mechanism of the adverse reaction means that the incidence of breakthrough bleeding can rise by 50% as well as boost ovulation levels within 16 women over 2 months when co-administering therefore, rising the possibility of unintended pregnancy (Horn et al, 2018). To prevent this adverse reaction these drugs shouldn’t be co-administered.
 
OCP’s can affect the body’s processing of nutrients and minerals which may result in depletion of vital minerals necessary optimal functioning. Nutrients include B vitamins (B9, B2, B6, B12), vitamin C and E, as well as minerals including magnesium, zinc and selenium (Palmery, 2013). Zinc is an essential mineral that plays a role in metabolism and gene expression. The use of OCP’s reduces plasma levels of zinc due to lower absorption (Palmery et al, 2013). Selenium is a micronutrient that aids in the reduction of carcinogens and has responsibility within thyroid function. Studies reveal that OCP's inhibit selenium absorption (Palmery et al, 2013). Magnesium is essential for biological performance, within ATP function and DNA/RNA-synthesis. Over three hundred enzymes require magnesium for their catalytic purpose. OCP’s have been shown to reduce serum magnesium levels and thus increase the risk of developing thrombosis (Palmery et al, 2013). Therefore, serum levels of these important dietary nutrients and minerals need to be made aware to patients, supplementation or alternative contraception may need to be considered to maintain optimal nutritional status.
 
Adverse reactions that occur when taking COC’s usually diminish with continued use. To prevent adverse reactions, patients with any unusual symptoms are advised to switch the subscription to provide benefits. By switching to an alternative COC’s it is recommended that a new pill packet is begun without a time gap to ensure contraceptive protection is continued, other defence mechanisms should be used during this time (International Agency for Research on Cancer, 2012). Adverse effects involving hormones can be avoided by switching pills in relation to their oestrogenic or progestogenic dominance. Studies show that lower levels of oestrogen and higher levels of progesterone are associated with fewer side effects including fluid retention and nausea (Barr et al, 2010). To avoid the risk of unplanned pregnancy, women who have taken antibiotics are advised to use other contraceptives for at least seven days’ post-treatment. Reducing the risk of nutritional deficiencies is also important when using COC’s. This involves testing for appropriate levels as well as supplementation of the B vitamins, vitamin C and E, zinc, magnesium and selenium to function optimally, prevent health issues and to reduce adverse reactions of COC’s. 
 
Monophasic oral contraceptive pills are relatively safe and are a highly effective contraception choice that results in protection from an unplanned pregnancy as well as other therapeutic benefits such as lower volumes of blood during menses. There are potential individual risk factors involved in this form of contraception and some women should approach COC’s with caution due to their individual health issues, however with proper guidance and adhering to the cyclical manner of this pill they can be avoided.