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British Journal of & Medical Research 15(11): 1-8, 2016, Article no.BJMMR.25257 ISSN: 2231-0614, NLM ID: 101570965

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M. Najimudeen 1* and K. Sachchithanantham 1

1Melaka Manipal Medical College, .

Authors’ contributions

This work was carried out in collaboration between both authors. Author MN designed the study and wrote the manuscript. Author KS revised and edited the manuscript. Both authors read and approved the final manuscript.

Article Information

DOI: 10.9734/BJMMR/2016/25257 Editor(s): (1) Honggang Li, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. (2) E. Umit BAGRIACIK, Department of Immunology, Gazi University, . (3) Salomone Di Saverio, Emergency Surgery Unit, Department of General and Transplant Surgery, S. Orsola Malpighi University Hospital, Bologna, . Reviewers: (1) Anonymous, University of Ilorin, Nigeria. (2) Joyce Kinaro, University of Nairobi, . (3) Milena Bastos Brito, Campus Universitário - Monte Alegre, . (4) Anonymous, Babcock University Ilishan Remo, Nigeria. Complete Peer review History: http://sciencedomain.org/review-history/14697

Received 25 th February 2016 th Mini-review Article Accepted 12 May 2016 Published 18 th May 2016

ABSTRACT

Millions of women are in the reproductive age group. Their age vary from 15 to 50 years. They differ in life style, culture and body mass index. They may have morbidities like high blood pressure, disease and other co-morbidities. They are prone to venous , malignancies of the breast and endometrium. Therefore the prescription of contraception should be on individual basis. Over the past 40 years there had been many improvements in the contraceptive methods. The 50 microgram ethinyl oestradiol of the combined pill was reduced drastically. Many rods of the norplant had become a tiny single rod implanon. The inert Lippi’s loop has transformed into -releasing intra uterine system (LNG-IUS). When there are varieties of contraceptive methods available, it is obvious that no method is perfect and full proof to prevent conception. It is important for the caring practitioner to select the most appropriate method to suit each individual client.

Keywords: Contraception; oestrogen; . ______

*Corresponding author: E-mail: [email protected];

Najimudeen and Sachchithanantham; BJMMR, 15(11): 1-8, 2016; Article no.BJMMR.25257

1. INTRODUCTION implants. They should not take -only injectables (POIs) (DMPA or NET-EN) before 42 Combined hormonal contraceptive oral pills days of delivery. From 6 weeks to 6 months of (CHC) are the combination of oestrogen and delivery can use POPs, POIs, and LNG and ETG progesterone. The oestrogen is essentially implants without restriction. After 6 months of ethinyl oestradiol (EE). The first formulation in delivery can use POPs, POIs, and LNG and ETG 1960 has 150 µg de [1]. The EE implants without restriction [4]. strength in the year 1960 was 50 microgram but now it is 35 to 20 microgram. The progesterone within 4 weeks of delivery can use had varied from time to time. The first generation the progesterone-releasing without was , , 2 nd restrictions. generation was Levonorgestrel, 3 rd generation , , and the LNG-IUD use among breastfeeding women: 4th generation is , , Breastfeeding women within 4 weeks of delivery acetate. should not have an LNG-IUD inserted After 4 weeks they can be inserted. In this article the low-dose (35 or less than 35 microgram ethinyl oestradiol) combined oral CHC can increase the risk of arterial thrombosis contraceptive pills, combined injectable in complicated valvular heart disease.Among contraceptive contraceptives (CICs), combined women with valvular heart disease (VHD), CHC vaginal ring (CVR), progesterone only pills use may further increase the risk of arterial (POP), Depot medroxy progesterone acetate thrombosis. In uncomplicated VHD the hormonal (DMPA), (NETEN), contraceptives outweighs the risk but in women levonorgestrel (LNG) and (ETG) with complicated valvular heart disease like implants, emergency contraceptive pills (ECPs), pulmonary hypertension, atrial fibrillation and Levonorgestrel-releasing IUDs (LNG-IUDs) and sub acute bacterial endocarditis the risk is Progesterone releasing vaginal ring (PVR) are serious and should be avoided. discussed. Women who has diabetes mellitus for less than

20 years and no vascular disease can choose 2. DISCUSSION any of the hormonal methods- combined (pill, patch, ring), POP, progesterone injections, 2.1 Combined Hormonal Contraceptive implants and LNG-IUS. Women who suffer from Preparations diabetes for more than 20 years or with vascular lesions should avoid oestrogen containing 2.1.1 Combined hormonal contraceptive oral preparations and choose only progesterone pills (CHC) preparations like POP, implants and LNG-IUS [5]. Age alone is not a risk factor for the use of hormonal contraceptives. After 40 years the risk Since the people with SLE are at increased risk of cardiovascular disease increases and may of ischaemic heart disease, stroke and also increase with CHC use. In the absence of venous thromboembolism., the CHC is not other adverse clinical conditions, CHCs can be recommended. Current evidence suggests that used until menopause [2]. COCs containing levonorgestrel, norethisterone and norgestimate are associated with the lowest The breast feeding mothers should not use risk of venous thrombo embolism [6]. CHCs within 6 weeks of delivery. It is better to avoid from 6 weeks to 6 months. After the Antiretroviral therapy (ART) can alter the 6months of delivery the CHCs are safe .If they bioavailability of hormone in the are not breastfeeding they should avoid for only combined hormonal contraceptives. If at all 21 days of postpartum period. The mothers with preparations with ethinyl oestradiol 30 microgram deep venous thrombosis risk should avoid for 42 should be used along with barrier methods. This days. After 42 days of delivery all mothers can is to ensure additional safety of contraception use CHCs [3]. and sexual transmission of infection. Women taking Nucleoside / nucleotide reverse Breastfeeding mothers within 42 days of delivery transcriptase inhibitor (NRTI) can use the can use progestogen-only pills (POPs) and following hormonal contraceptive methods levonorgestrel (LNG) and etonogestrel (ETG) without restriction: COCs, CICs, combined

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Najimudeen and Sachchithanantham; BJMMR, 15(11): 1-8, 2016; Article no.BJMMR.25257

contraceptive patches and rings, POPs, POIs It is recommended to await 42 days after delivery (DMPA and NET-EN),and LNG and ETG to start combined contraception in patient with implants Women taking any NRTI can generally other risk factors for VTE [2]. use the LNG-IUD provided that their HIV clinical disease is asymptomatic or mild Women living 2.1.2 Combined injectable contraceptives with severe or advanced HIV clinical disease and (CICs) taking any NRTI generally should not initiate use of the LNG-IUD until their illness has improved to Two CIC formulations mostly prescribed are: asymptomatic or mild HIV clinical disease. (a) Cyclofem = acetate Women taking any NRTI who already have had 25 mg plus cypionate 5 mg. an LNG-IUD inserted and who develop severe or (b) Mesigyna = norethisterone enanthate 50 advanced HIV clinical disease need not have mg plus 5 mg. their IUD. As CICs are administered by injection, the first- Anticonvulsant can reduce the pass metabolism by the liver is avoided, thereby potency of CHC. They should use barrier minimizing estradiol’s effect on the liver. The methods in addition to CHC. gastro intestinal side effects are eliminated. It is COCs are metabolised by the liver, and their use useful to the women who cannot remember to may adversely affect women whose liver function take oral pill daily. is compromised. It may enhance the existing gall-bladder disease. It is not recommended in Their potency and side effects are almost similar women with past history of cholestasis. COCs, to COC. Their contraindications are similar to CICs, P or CVR may cause a small increased that of COC. They cannot be prescribed in the risk of gall bladder disease. There is also presence of phospholipid antibodies, migraine concern that COCs, CICs, P or CVR may worsen with aura, current history of breast cancer, existing gall bladder disease. Unlike COCs, CICs endometrial and ovarian cancer, decompensated have been shown to have minimal effect on liver liver cirrhosis, hepato cellular adenoma and function in healthy women, and have no first- malignant hepatoma. pass effect on the liver. History of - related cholestasis may predict an increased risk 2.1.3 Contraceptive vaginal ring (CVR) of developing COC-related cholestasis. CVR is a flexible, transparent, plastic ring. It is Some of the can alter the potency of placed in the vagina where it releases two oral contraceptives. Rifampicin and Rifabutin are hormones – oestrogen and progestogen. CVR enzyme inducing substances and enhances the releases etonogestrel 120 microgram and ethinyl clearance of oral contraceptives. Therefore the estradiol 15 microgram daily. hormonal level in the blood is reduced and contraceptive efficacy is also reduced. Rifampicin Unlike the diaphragm, the mechanism of action is is given to treat tuberculosis and Rifabutin entirely dependent on the absorption of sex is administered to treat infection with and not any barrier mechanism. Thus, Mycobacterium avium complex-MAC. If these the CVR has to be in contact with the vaginal antibiotics are given for more than 2 months epithelium but not fitted in the vagina or over the another back up contraception is required. cervix. Breast cancer is a hormonally sensitive tumour, and the prognosis of women with current or The diameter is 54 mm. The vaginal ring should recent breast cancer may worsen with CHC be left in the vagina for three weeks (21 days At use.COC use reduces the risk of developing the end of 21 days the ring will be removed and endometrial cancer and ovarian cancer [7]. another ring is inserted after the 7 days of ring free interval. COCs may not be a suitable method for women with impaired circulation or immobile extremities, Unlike the CHC, the rings are inserted once a even in the absence of known thrombogenic month only. The gastro intestinal symptoms are mutations because of concerns about an avoided. Other than these the potency and increased risk of DVT. considerations are similar to that of CHC.

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Najimudeen and Sachchithanantham; BJMMR, 15(11): 1-8, 2016; Article no.BJMMR.25257

2.1.4 The (g) Current breast cancer. (h) Diabetic Nephropathy / retinopathy/ The contraceptive patch is a sticky patch neuropathy and other vascular disease or measuring 5x5 cm and .contact surface area of diabetes of more than 20 years’ duration. 20 cm. Each patch lasts for one week. A woman (i) Severe decompensated liver cirrhosis and applies her first patch onto her upper outer arm, Malignant (hepatoma) of the liver. buttocks, abdomen or thigh on either the first day of her menstrual cycle (day 1) or on the first 2.2 Progesterone Only Preparations Sunday following that day The patch is changed every week for three weeks after a patch free 2.2.1 Progestogen-only pills (POPs) interval of one week again the patch is commenced. (Patch for 3 week and no patch for POPs contain only a progestogen and no one week). .

It contains 6.00 mg (NGMN) and The action of POP is mainly by thickening the 0.75 mg ethinyl estradiol (EE). The transdermal cervical mucous and makes the ascent of patch was designed to deliver EE and NGMN spermatozoa difficult. Therefore their efficacy is over a seven-day period while oral relatively less compared to CHC. contraceptives (containing NGM 250 mcg / EE 35 mcg) are administered on a daily basis. Desogestrel 75 microgram (Cerazette) to be taken daily within 12 hours of interval , where as The most common adverse reactions reported diacetate 500 microgram (Femulen), during clinical trials were breast symptoms, Norethisterone 350 microgram ( Micronor) , application site disorder, nausea, Norethisterone 350 microgram (Nriday) and dysmenorrhea and abdominal pain. The most Levonorgestrel 30 microgram( Norgeston) should common events leading to discontinuation were be taken within 4 hours of interval [8]. application site reaction, breast symptoms (including breast discomfort, engorgement and The desogestrel 75 microgram preparation is as pain), nausea and vomiting, headache and effective as combined pills [9]. emotional lability. Age, obesity and smoking are not factors Since it contains oestrogen and progesterone the influencing the prescription. Therefore POP are usage and limitations are almost similar to that of ideally suitable for elderly obese women who are COC. Contraindications for combined injectable heavy smokers. contraceptives are the same as oral [2]. The POP can be started 21 days after the Oestrogen containing preparations (Combined delivery. In the case of it can be oral contraceptive pills, patches, vaginal ring and commenced after 5 days of occurrence. combined injectable preparations are not advisable in the following patients: Women should be advised that changes in bleeding patterns with progestogen-only pill use (a) Women over 35 years who smoke more are common: 2 in 10 women have no bleeding, 4 than 15 cigarettes daily. in 10 women have regular bleeding and 4 in 10 (b) Multple risk factors for arterial cardio- women have irregular bleeding. vascular disease (obesity, smoking, diabetes, old age and hypertension) BP There is no evidence of association between more than 160/100 and vascular disease. progestogen-only pill use and weight change. (c) Known thrombogenic mutations (e.g Factor V Leiden, prothrombin mutation, protein S, 2.2.2 Progestin-only injectable contraceptives Protein C and antithrombin deficiencies) (d) Current history of ischaemic heart disease Progesterone only injectable include depot and history of cerebrovascular accident. medroxyprogesterone acetate (DMPA) and (e) Complicated valvular heart disease norethisterone enanthate (NET-EN).There are (pulmonary hypertension, risk of atrial three formulations considered here: fibrillation, history of subacute bacterial endocarditis). (a) DMPA-IM = 150 mg of DMPA given (f) Migraine with aura at any age. intramuscularly.

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Najimudeen and Sachchithanantham; BJMMR, 15(11): 1-8, 2016; Article no.BJMMR.25257

(b) DMPA-SC = 104 mg of DMPA given arm at the inner side of the non-dominant upper subcutaneously. arm about 8-10 cm (3-4 inches) above the medial (c) NET-EN = 200 mg of NET-EN given epicondyle of the humerus. The Implanon is a intramuscularly. long-acting (up to 3 years) and to be replaced with a new one at the end of 3 years. It is single, DMPA-SC and, therefore, DMPA-SC should off-white, soft, flexible, ethylene vinylacetate have the same categories as DMPA-IM; (EVA) implant, 4 cm in length and 2 mm in diameter containing 68 mg etonogestre. It Depo Medroxy progesterone acetate (DMPA 150 releases 60 to 70 mcg/day in first 5 to 6 weeks mg) has better compliance since 3 monthly and decreases to approximately 35 to 45 intramuscular injection. Suitable for mcg/day at the end of the first year, to breastfeeding mothers. The disadvantages are approximately 30 to 40 mcg/day at the end of the weight gain, menstrual irregularities such as second year, and then to approximately 25 to 30 irregular bleeding and amenorrhoea, abdominal mcg/day at the end of the third year. cramps, discomfort. Fertility can be delayed as long as 10-12 months after last It may be used during breastfeeding 4 weeks injection...Valvular and complicated congenital after delivery. heart diseases are not contraindicated for the use of DMPA. It is not suitable for women with current or past history of thrombosis or thromboembolic For women under 18 years of age, there are disorders, liver tumors, benign or malignant, or theoretical concerns regarding the hypo- active , undiagnosed abnormal estrogenic effects of DMPA use, including genital bleeding known or suspected breast whether these women will achieve their cancer and personal history of breast cancer, or appropriate peak bone mass. DMPA can be other progestin-sensitive cancer, now or in the continued to age 50 years and then stopped and past [10]. a suitable alternative contraceptive. Smokers can use implanon [2]. 2.2.3 Progestogen-only implants 2.2.4 Progesterone releasing IUCDs Progestogen-only implants are a type of long- acting, reversible contraception. The various The LNG-IUS has vertical stem containing types of implants that are considered here are 52 mg levonorgestrel (LNG) mixed with the following: polydimethylsiloxane. It releases 20 micrograms LNG per day. It is effective, reversible method of 2.2.3.1 Levonorgestrel (LNG) contraception with a failure rate of less than 1 per 100 woman-years. Ideally, the LNG-IUS should The LNG-containing implants are Norplant, be inserted in the first 7 days after the onset of Jadelle and Sino-implant (II).a. Norplant is a 6- menstruation. rod implant, each rod containing 36 mg of LNG (no longer in production). IUCD could be inserted the first 48 h or after 6 weeks due to expulsion rates. Perforation are not (i) Jadelle is a 2-rod implant, each rod increased during postpartum insertion [2]. containing 75 mg of LNG. (ii) Sino-implant (II) is a 2-rod implant, each This is suitable option for women who need rod containing 75 mg of LNG. contraception and treatment for menorrhagia (iii) Etonogestrel (ETG): The ETG-containing omen should be informed that the LNG-IUS is implants are Implanon and Nexplanon. licensed for 5 years’ use LNG-IUS can reduce Both consist of a single-rod implant menstrual blood loss by over 90%. Return of containing 68 mg of ETG. fertility following LNG-IUS removal.

Norplant is a subcutaneous contraceptive with The most likely cause of LNG-IUS failure is levonorgestrel and implanon is etonogestrel expulsion. The risk of is around 1 in 20 [11]. releasing implant. The IUCDs are not very popular methods since Implanon is a progesterone only single rod there are so many non-planning pregnancy in the implant and inserted subdermally in the upper world [12].

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Current purulent cervicitis, chlamydia and The levonorgestrel-releasing intrauterine system gonorrhoea infections and pelvic tuberculosis, is currently under evaluation for use as EC. The distortion of uterine cavity due to anomalies or Copper IUCD could be used as emergency fibroids, endometrial cancer and ovarian cancer contraception. contraindicated for the insertion of IUCD. In the event of puerperal sepsis and post septic Return of fertility occurs within few months with , the infection must be completely treated the exception of DMPA (10 months delay) and before the insertion of the IUCD. NET-EN (6 months) from the date of the last injection regardless of the duration of their use. The chances of subsequent ectopic are more in women who had ectopic pregnancy. 3. FUTURE HORMONE PREPARATION The IUCDs prevent intrauterine pregnancy more than extrauterine pregnancy. Therefore the MicroCHIPS, an IT start-up company with links to relative likelihood of ectopic pregnancy is greatly Massachusetts Institute of Technology, is increased. developing a radical new contraceptive - a tiny (a) Women with SLE are at increased risk of microchip implanted under the skin that can be ischaemic heart disease, stroke and operated wirelessly by remote control. Micro venous thromboembolism. CHIPS is a device measuring just 20 x 20 x 7 (b) Positive (or unknown) antiphospholipid mm designed to be implanted under the skin of antibodies – LNG IUS to be avoided. the buttocks, abdomen or upper arm. (c) Gestational Trophoblastic Disorders – Both types of IUCD should be avoided. When a woman wishes to conceive, she simply (d) IUCD should be avoided in active pelvic turns off the device with a remote. The chip infection, vaginal bleeding of undiagnosed would not need to be removed from the woman aetiology, carcinoma of endometrium and until 16 years of use have elapsed. By contrast, cervix. current hormonal birth control implants last a maximum of 5 years. 2.3 (EC) The levonorgestrel is contained on the chip using Half of all pregnancies in the are a hermetic titanium and platinum seal developed unintended [13]. by MicroCHIPS. The hormone is released by passing an electric current from an internal Three types of emergency contraceptions (EC) battery through the seal, which melts it are available. temporarily, allowing a small dose of levonorgestrel to be released each day. This can These should be taken within 72 hours of sexual be used up to 16 years. exposure.

(a) Levonorgestrel can be given as 0.75 mg MicroCHIPS, with the backing of Bill Gates, plan one tablet and another 0.75 mg tablet after to submit the implant for preclinical testing in the 12 hours. Studies had shown that single US next year, and believe that the device could dose of 1.5 mg is equally effective and this go on sale by 2018. dose is convenient [14]. (b) 30 mg single dose is The effectiveness of any contraceptive method equally effective and well tolerated. This depends on consistent and correct use. The appears to be popular in many countries efficacy vary between the typical and perfect use. when is imminent, UPA is more With regard to the male condom, the percentage effective than levonorgestrel [15]. of women experiencing an unintended pregnancy (c) In Yuzpe method an OCP containing within the first year of use in typical is 15 but in ethinyl oestradiol and levonorgestrel are perfect is only 2. taken. In OCP containing EE 120 microgram and LNG 0.60 mg, altogether 4 4. CONCLUSION tablets to be taken .Two tablets are taken first and 2 tablets to be taken after 12 Birth spacing is the birth right of a woman. Too hours of first dose. When the ECP such as frequent pregnancies are associated with UPA and LNG are not available the Yuzpe adverse maternal and child health outcomes, method is useful [16]. include delayed prenatal care, premature birth,

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Peer-review history: The peer review history for this paper can be accessed here: http://sciencedomain.org/review-history/14697

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