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Oral Contraceptives - Journey So Far: a Review Kanaka Bhushanam GVVS1 and Sakuntala Devi Gampa2,*

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Oral Contraceptives - Journey So Far: a Review Kanaka Bhushanam GVVS1 and Sakuntala Devi Gampa2,* REVIEW Oral contraceptives - journey so far: A review Kanaka Bhushanam GVVS1 and Sakuntala Devi Gampa2,* 1 2 Gitam Medical Collage, Gandhi Nagar, Rushikonda, Visakhapatnam, Andhra Pradesh, India Krishna Institute of Medical Sciences, Minister Road, Secunderabad-500003, Telangana, India Abstract since 1970s. As per WHO (1998), over 100 million women are using oral contraceptive pills (OCPs) worldwide, mostlyOral contraceptive in developed is acountries. widely accepted In India and only most 2% effectiveof married method women of offertility reproductive control. ageIts wereuse has using been OCPs growing for fertility control during the period from 1990 to 2001. The history, evolution and development of oral pills till Keywords:date is discussed oral contraception; along with the fertility benefits, control; risks and contraceptive side effects pills of oral contraceptive pills. *Corresponding author: Dr. Sakuntala Devi Gampa, Gitam Introduction Medical Collage, Gandhi Nagar, Rushikonda, Visakhapatnam, [email protected] Once upon a time contraception was a taboo in many countries and practicing or even promoting ReceivedAndhra Pradesh, 28 October India. 2015; Email: Revised 11 December 2015; Accepted 19 December 2015; Published 29 December 2015 contraception was punishable. From that situation oral pills have now reached a stage where they are Citation: most widely accepted method of birth control and Kanakabhushanam GVVS, Gampa SD. Oral1 contraceptives- also became a useful therapeutic modality for many journey so far: A review. J Med Sci Res. 2016; 4(1):35-40. DOI: gynaecological conditions avoiding unnecessary Chttp://dx.doi.org/10.17727/JMSR.2016/4-01opyright: © 2016 Kanakabhushanam GVVS, et al. Published by hysterectomies. Many breakthroughs in the article distributed under the terms of the Creative Commons evolution of birth pills are responsible for today’s AttributionKIMS Foundation License, and which Research permits Center. unrestricted This is use, an distribution,open-access high acceptance of oral pills in fertility control and and reproduction in any medium, provided the original author and source are credited. Htheiristory other and clinical evolution uses and benefits. Since ages human beings have attempted to invent and use contraception. In the past oral contraception was practiced with herbs, roots, minerals and oils. contraception. Oral pill is a major breakthrough in the field of money of Katherine McCormi, the pharmacological geniusEven though of Gregorythe passion Pincus of Margaret and the Sanger, clinical the Vol. 4 | Issue 1 | January - March 2016 35 of oral contraceptive pill, Gregory Pincus (Figure1) containing 10mg of norethinodrel and 150mg of nameresponsibility is associated of John withRock oralresulted pill. in First the inventionpill was meThusstranol in 1957was developedfirst contraceptive by Searle Company.pill “enovid” First developed in 1961. Since then several stepwise it was approved by FDA only for the treatment of changes in dosage and composition of pill have taken menstrual disorders and later it got approved as contraceptive in 1961. However Searle did not market enovid 10mg as contraceptive pill as they developed place in order to get a safe and effective pill. low dose enovid with 5/2.5mg of norethinodrel and got approval in 1961 for oral contraception. In earlyand 75mg 60s Scheringof mestranol, developed which isoralpill equally containing effective 4mg of norethisterone and 50mg of ethynylestradiol (anovlar). Organon developed “lyndiol” (2.5 mg of lynestrenol Hohlweg& 75mg inof 1938 mestranol). and later itEthinyl replaced estradiol mestranol was in synthesized by Hans Herloff Inhoffen and Walter sequential pill in which oestrogen will be given forall OC2 pills.weeks Joseph followed Goldzieher by oestrogen was first along to develop with progesterone, for one week. Pills with natural oestrogens have been developed very recently. Knowledge of the fact that high doses of sex steroids Figure 1: (standing behind him). Katherine McCormi. particularly ethnylestradiol are responsible for the Gregory Pincus (at the microscope) and John Rock of newer pills with low dose oestrogen, newer Milestones serious side effects of pills, led to the development In 1921, Ludwig Haberlandt, grandfather of administrative routes and schemes . This resulted pill found that rabbits and guinea pigs became inprogestins the development with more specificof combined action andpills alternative & phasic temporarily sterile after transplantation of ovaries pills. Due to dose reduction, extension of pill intake suppression of follicular development. Only in the from pregnant animals. This finding led to the study recentto 24 dayspast, becamethe extended necessary regimens to ensure are promoted. sufficient of the effect of progesterone on ovulation. In 1937, Besides, ‘progesterone only’ pills have also been A. W. Makepeace and co- workers demonstrated Marker, organic chemistry professor found that developed for use in women in whom oestrogen progesteronethe anti-ovulatory can be effect synthesized of progesterone. from a substance Russell Dioscorea mexicana. Gregory Pincus along with nausea,use is breastcontraindicated. tenderness, Even vomiting, though and the bloating, dose Min“diosgenin” Chueh Changextracted found from that therepeated root injectionsof plant reduction resulted in reduction of side effects like of progesterone stopped ovulation in animals. Carl of progestin on endometrium even in low dose is dominant.the pro thrombotic effect is not nullified. The effect orally active progestin ‘norethindrone’. Djerassi (syntex company) synthesized the first The newer progestins are 2nd generation Frank Colton (Searle) developed close isomer of (levonorgestrel); 3rd generation (gestodene norethindrone namely norethinodrel. First oral and desogestrel); 4th generation (drospirinone, contraceptive trials were started with norethinodrel. Subsequently it was found that addition of a attempts to replace ethynylestradiol with natural synthetic esrogen mestranol stops the breakthrough oestrogendienogest (estradiol)& normogestrol); resulted inNatural the development estradiol of- bleeding. a four phasic pill, a combination of estradiolvalerate 36 Journal of Medical and Scientific Research which is cleaved into estriol and dienogest in an and extended cycle of 26/28 days. once in a month. pills that can be used less frequently - may be A second OC containing 17 alpha estradiol and Classification of steroidal contraceptives normogestrol acetate 24/4 regimen is about to be launched. In 1980 low dose pills containing 0.015 has been tried through various routes in order to Estrogen and/or progesterone administration are frequently used now. Research is currently going provide a reliable contraceptive cover. Various types -0.025 mg of ethinyl estradiol are developed, which of available steroidal contraceptives are shown in used only in post ovulatory phase or following coitus on to develop non-steroidal pills, pills that can be Steroidal Contraceptivesfigure 2. Oral Injectable Implants IUD (Progestasert) (Norplant), Mirena Combined Injectable Combined contr. (DMPA,Contraceptive) NET-EN, patch/ring Combined Single preparations (Containing only Progestogen) Monophasic Triphasic Mini pill contraceptive pill Post-coital Standard dose Very low dose (Mala D/Mala N) Low dose (EE 0.3 mg) (EE 0.5 mg) (EE 0.2 mg) Figure 2: Steroidal contraceptives. Classification Depending upon the amount of oestrogen and type of ethinyl estradiol and progestin drosperenone/ dienorgest/desogestrel/ normegestrol. gestodine 4th generation with 20-30µg 1stof progesterone, generation pillswith are 50µg classified of ethinyl below: estradiol Oral pills and progestin noretynodrel, 2nd generation combined pill, and 2) progesterone only pill or mini levonorgestrel/norgestimate 3rd generation pillOral pills are broadly divided in to two groups: 1) with 20-35µg of ethinyl estradiol and progestin multiphasic. Combined pills are of two types - monophasic or Vol.with 4 20-30µg | Issue 1 of | ethinyl January -estradiol March 2016 and progestin 37 Monophasic pills Newer oral contraceptives Monophasic pills contain oestrogen and progestin in Nupil (noperalate): Chewable pill. Ovacon 35; the same amount in each pill. They are again divided contains progesterone (norethindrone) and into a) low dose pills containing ethinyl estradiol less oestrogen ethinyl estradiol. It is available as 28 day than 0.05mg and b) very low dose pills with ethinyl regimen. After chewing the pill they have to take estradiol less than 0.015-0.025 mg in each pill along 8-oz of water. with progestins. Alternative routes and administration Multiphasic pills These include hormone releasing intrauterine With a view to reduce total monthly dose of steroids, contraceptive device (IUCD), injectable phasic pills have been introduced. They contain contraceptives, implants, vaginal rings and dermal low doses and variable amount of oestrogen and patches. Vaginal rings and dermal patches came progestogen in 2 (biphasic) or 3 (triphasic) periods in to market in 2001. Parenteral route has got with in a menstrual cycle. The dose of progestin is low at the beginning and high at the end, while There is no evidence that these new modalities of the advantage of bypassing the 1st pass effect. oestrogen dose is constant or slightly rises in mid administration are superior to OC pills. cycle. Biphasic pill contains 0.035mg of ethinyl estradiol and low dose progestogen for 10 days Mechanism of action
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