Editing Combined oral contraceptive pill (section)

==Background==
===Oral contraceptives===
[[File:Progesterone.svg|thumb|176x176px|chemical structure of Progesterone]]
[[File:Estradiol.svg|thumb|176x176px|chemical structure of Oestrogen]]
{{unreferenced section|date=December 2024}}
'''Hormonal oral contraceptives''' are preventive [[medication]]s taken [[Orally disintegrating tablet|orally]] by [[female]]s to avoid [[pregnancy]] by manipulating their [[sex hormone]]s. The first oral contraceptive was approved by the US [[Food and Drug Administration]] (FDA) and sold to the market in 1960. There are two types of hormonal oral contraceptives, namely Combined Oral Contraceptives and [[Progestin|Progesterone]] Only Pills. Oral contraceptives, be it combined or progesterone-only, can effectively prevent pregnancy by regulating hormonal changes in the [[menstrual cycle]], inhibiting [[ovulation]], and altering [[Cervix|cervical]] [[mucus]] to impede [[sperm]] mobility; combined pills have extra effects in menstrual cycle regulation and menstrual pain relief. Common [[off-label use]]s include [[menstrual suppression]] and [[acne]] relief, with Combined Oral Contraceptives having additional benefits in relieving menstrual [[migraine]].

=== Variants ===
'''Progesterone-only pills''' ('''POPs''') utilise [[Progestogen (medication)|progestin]], the synthetic form of [[progesterone]], as the only active pharmaceutical ingredient in the formulation.<ref name=":0a" /><ref>{{Citation |last1=Edwards |first1=Michael |title=Progestins |date=2024 |work=StatPearls |url=http://www.ncbi.nlm.nih.gov/books/NBK563211/ |access-date=2024-02-28 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=33085358 |last2=Can |first2=Ahmet S.}}</ref> In the US, [[drospirenone]] and [[Norethisterone|norethindrone]] are the most commonly used compounds in formulations.<ref name=":0" />

'''Combined oral contraceptives''' ('''COCs''') are commonly classified into generations, referring to their order of development in history.<ref name=":3a">{{Cite web |title=Combined hormonal contraceptives {{!}} European Medicines Agency |url=https://www.ema.europa.eu/en/human-regulatory-overview/post-authorisation/pharmacovigilance-post-authorisation/referral-procedures-human-medicines/combined-hormonal-contraceptives |access-date=2024-02-28 |website=www.ema.europa.eu|date=12 July 2013 }}</ref> This discussion may also help identify some key features in a variety of products. According to [[European Medicines Agency|EMA]], the first generation of combined oral contraceptives, which made use of a high concentration of oestrogen only, were those invented in the 1960s.<ref name=":3a" /> In the second generation of products, progestogens were introduced into the formulation while the concentration of oestrogen was reduced.<ref name=":3a" /> Starting from the 1990s, the progression in the development of combined oral contraceptives has been directed towards varying the type of progestogen incorporated.<ref name=":3a" /> These products are referred as the third and fourth generation.<ref name=":3a" />

Oestrogen ingredients: [[Estradiol (medication)|estradiol]], [[ethinylestradiol]], [[Estetrol (medication)|estetrol]].<ref name=":0a" />

1st generation progestin: [[Norethisterone acetate|norethindrone acetate]], [[Etynodiol diacetate|ethynodiol diacetate]], [[lynestrenol]], [[Noretynodrel|norethynodrel]].<ref name=":0a" />

2nd generation progestin: [[levonorgestrel]], [[Norgestrel|dl-norgestrel]].<ref name=":0a" />

3rd generation progestin: [[norgestimate]], [[gestodene]], [[desogestrel]].<ref name=":0a" />

=== The menstrual cycle ===
[[File:Menstrual cycle.svg|thumb|279x279px]]
Hormonal oral contraceptives (HOCs) interact with hormonal changes in the menstrual cycle in females to prevent [[ovulation]], and hence achieve contraception.<ref name=":0a">{{Citation |last1=Cooper |first1=Danielle B. |title=Oral Contraceptive Pills |date=2024 |work=StatPearls |url=http://www.ncbi.nlm.nih.gov/books/NBK430882/ |access-date=2024-02-28 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=28613632 |last2=Patel |first2=Preeti |last3=Mahdy |first3=Heba}}</ref> In a 28-day menstrual cycle, there are the proliferative phase, ovulation, and then the secretory phase.<ref name=":1a">{{Citation |last1=Thiyagarajan |first1=Dhanalakshmi K. |title=Physiology, Menstrual Cycle |date=2024 |work=StatPearls |url=http://www.ncbi.nlm.nih.gov/books/NBK500020/ |access-date=2024-02-28 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=29763196 |last2=Basit |first2=Hajira |last3=Jeanmonod |first3=Rebecca}}</ref>

Menstruation marks the beginning of proliferative phase in day 1-14.<ref name=":1a" /> In this period, the [[pituitary gland]] located near the [[brain]] secretes [[follicle-stimulating hormone]] (FSH) into the [[bloodstream]] to signal the development of [[Ovarian follicle|follicle]] in [[ovary]] in the [[female reproductive system]].<ref name=":1a" /> While follicle serves as the chamber of ovum development, it secretes [[Estrogen|Oestrogen]], a hormone that not only triggers the thickening of [[Endometrium|uterine lining]] in preparation for [[Implantation (embryology)|implantation]], but also inhibits the secretion of FSH in pituitary via a [[Negative feedback|negative feedback mechanism]].<ref name=":1a" />

Specifically in ovulation, transient positive feedback by Oestrogen on FSH and [[Luteinizing hormone|Luteinising Hormone]] (LH) secretion from pituitary is permitted so that the release of mature [[Egg cell|ovum]] from follicle is triggered.<ref name=":1a" />

In secretory phase on day 14-28, this follicle then transforms into [[corpus luteum]] and continues releasing Oestrogen with [[Progesterone]] into bloodstream.<ref name=":1a" /> While Oestrogen and Progesterone primarily aid the maintenance of thickness in uterine lining,<ref name=":1a" /> the negative feedback in pituitary allows them to inhibit FSH and LH secretion.<ref name=":1a" /> In the absence of LH, corpus luteum degenerates and ultimately causes blood Oestrogen and Progesterone levels to decline.<ref name=":1a" /> Without these thickness maintaining agents, uterine lining breaks down and hence the presentation of menstruation.<ref name=":1a" />