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*Corresponding author: E-mail: najim5543@yahoo.com;
www.sciencedomain.org
Prescribing Hormonal Contraception
M. Najimudeen
1*and K. Sachchithanantham
11
Melaka Manipal Medical College, Malaysia.
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, Turkey. (3)Salomone Di Saverio, Emergency Surgery Unit, Department of General and Transplant Surgery, S. Orsola Malpighi University Hospital, Bologna, Italy.
Reviewers:
(1) Anonymous, University of Ilorin, Nigeria. (2)Joyce Kinaro, University of Nairobi, Kenya. (3)Milena Bastos Brito, Campus Universitário - Monte Alegre, Brazil. (4)Anonymous, Babcock University Ilishan Remo, Nigeria. Complete Peer review History:http://sciencedomain.org/review-history/14697
Received 25th February 2016 Accepted 12th May 2016 Published 18th 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, liver disease and other co-morbidities. They are prone to venous thrombosis, 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 Levonorgestrel-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; progesterone.
1. INTRODUCTION
Combined hormonal contraceptive oral pills (CHC) are the combination of oestrogen and progesterone. The oestrogen is essentially ethinyl oestradiol (EE). The first formulation in 1960 has 150 µg de mestranol [1]. The EE strength in the year 1960 was 50 microgram but now it is 35 to 20 microgram. The progesterone had varied from time to time. The first generation was Norethisterone, norethisterone acetate, 2nd generation was Levonorgestrel, 3rd generation Desogestrel, gestodene, norgestimate and the 4th generation is Drospirenone, dienogest, nomegestrol acetate.
In this article the low-dose (35 or less than 35 microgram ethinyl oestradiol) combined oral contraceptive pills, combined injectable contraceptive contraceptives (CICs), combined vaginal ring (CVR), progesterone only pills (POP), Depot medroxy progesterone acetate (DMPA), Norethisterone enanthate (NETEN), levonorgestrel (LNG) and etonogestrel (ETG) implants, emergency contraceptive pills (ECPs), Levonorgestrel-releasing IUDs (LNG-IUDs) and Progesterone releasing vaginal ring (PVR) are discussed.
2. DISCUSSION
2.1 Combined Hormonal Contraceptive Preparations
2.1.1 Combined hormonal contraceptive oral pills (CHC)
Age alone is not a risk factor for the use of hormonal contraceptives. After 40 years the risk of cardiovascular disease increases and may also increase with CHC use. In the absence of other adverse clinical conditions, CHCs can be used until menopause [2].
The breast feeding mothers should not use CHCs within 6 weeks of delivery. It is better to avoid from 6 weeks to 6 months. After the 6months of delivery the CHCs are safe .If they are not breastfeeding they should avoid for only 21 days of postpartum period. The mothers with deep venous thrombosis risk should avoid for 42 days. After 42 days of delivery all mothers can use CHCs [3].
Breastfeeding mothers within 42 days of delivery can use progestogen-only pills (POPs) and levonorgestrel (LNG) and etonogestrel (ETG)
implants. They should not take progestogen-only injectables (POIs) (DMPA or NET-EN) before 42 days of delivery. From 6 weeks to 6 months of delivery can use POPs, POIs, and LNG and ETG implants without restriction. After 6 months of delivery can use POPs, POIs, and LNG and ETG implants without restriction [4].
Breastfeeding within 4 weeks of delivery can use the progesterone-releasing vaginal ring without restrictions.
LNG-IUD use among breastfeeding women: Breastfeeding women within 4 weeks of delivery should not have an LNG-IUD inserted After 4 weeks they can be inserted.
CHC can increase the risk of arterial thrombosis in complicated valvular heart disease.Among women with valvular heart disease (VHD), CHC use may further increase the risk of arterial thrombosis. In uncomplicated VHD the hormonal contraceptives outweighs the risk but in women with complicated valvular heart disease like pulmonary hypertension, atrial fibrillation and sub acute bacterial endocarditis the risk is serious and should be avoided.
Women who has diabetes mellitus for less than 20 years and no vascular disease can choose any of the hormonal methods- combined (pill, patch, ring), POP, progesterone injections, implants and LNG-IUS. Women who suffer from diabetes for more than 20 years or with vascular lesions should avoid oestrogen containing preparations and choose only progesterone preparations like POP, implants and LNG-IUS [5].
Since the people with SLE are at increased risk of ischaemic heart disease, stroke and venous thromboembolism., the CHC is not recommended. Current evidence suggests that COCs containing levonorgestrel, norethisterone and norgestimate are associated with the lowest risk of venous thrombo embolism [6].
contraceptive patches and rings, POPs, POIs (DMPA and NET-EN),and LNG and ETG implants Women taking any NRTI can generally use the LNG-IUD provided that their HIV clinical disease is asymptomatic or mild Women living with severe or advanced HIV clinical disease and taking any NRTI generally should not initiate use of the LNG-IUD until their illness has improved to asymptomatic or mild HIV clinical disease.
Women taking any NRTI who already have had an LNG-IUD inserted and who develop severe or advanced HIV clinical disease need not have their IUD.
Anticonvulsant medication can reduce the potency of CHC. They should use barrier methods in addition to CHC.
COCs are metabolised by the liver, and their use may adversely affect women whose liver function is compromised. It may enhance the existing gall-bladder disease. It is not recommended in women with past history of cholestasis. COCs, CICs, P or CVR may cause a small increased risk of gall bladder disease. There is also concern that COCs, CICs, P or CVR may worsen existing gall bladder disease. Unlike COCs, CICs have been shown to have minimal effect on liver function in healthy women, and have no first-pass effect on the liver. History of pregnancy-related cholestasis may predict an increased risk of developing COC-related cholestasis.
Some of the medications can alter the potency of oral contraceptives. Rifampicin and Rifabutin are enzyme inducing substances and enhances the clearance of oral contraceptives. Therefore the hormonal level in the blood is reduced and contraceptive efficacy is also reduced. Rifampicin is given to treat tuberculosis and Rifabutin is administered to treat infection with Mycobacterium avium complex-MAC. If these antibiotics are given for more than 2 months another back up contraception is required.
Breast cancer is a hormonally sensitive tumour, and the prognosis of women with current or recent breast cancer may worsen with CHC use.COC use reduces the risk of developing endometrial cancer and ovarian cancer [7].
COCs may not be a suitable method for women with impaired circulation or immobile extremities, even in the absence of known thrombogenic mutations because of concerns about an increased risk of DVT.
It is recommended to await 42 days after delivery to start combined contraception in patient with other risk factors for VTE [2].
2.1.2 Combined injectable contraceptives (CICs)
Two CIC formulations mostly prescribed are:
(a) Cyclofem = medroxyprogesterone acetate 25 mg plus estradiol cypionate 5 mg. (b) Mesigyna = norethisterone enanthate 50
mg plus estradiol valerate 5 mg.
As CICs are administered by injection, the first-pass metabolism by the liver is avoided, thereby minimizing estradiol’s effect on the liver. The gastro intestinal side effects are eliminated. It is useful to the women who cannot remember to take oral pill daily.
Their potency and side effects are almost similar to COC. Their contraindications are similar to that of COC. They cannot be prescribed in the presence of phospholipid antibodies, migraine with aura, current history of breast cancer, endometrial and ovarian cancer, decompensated liver cirrhosis, hepato cellular adenoma and malignant hepatoma.
2.1.3 Contraceptive vaginal ring (CVR)
CVR is a flexible, transparent, plastic ring. It is placed in the vagina where it releases two hormones – oestrogen and progestogen. CVR releases etonogestrel 120 microgram and ethinyl estradiol 15 microgram daily.
Unlike the diaphragm, the mechanism of action is entirely dependent on the absorption of sex steroids and not any barrier mechanism. Thus, the CVR has to be in contact with the vaginal epithelium but not fitted in the vagina or over the cervix.
The diameter is 54 mm. The vaginal ring should be left in the vagina for three weeks (21 days At the end of 21 days the ring will be removed and another ring is inserted after the 7 days of ring free interval.
2.1.4 The contraceptive patch
The contraceptive patch is a sticky patch measuring 5x5 cm and .contact surface area of 20 cm. Each patch lasts for one week. A woman applies her first patch onto her upper outer arm, buttocks, abdomen or thigh on either the first day of her menstrual cycle (day 1) or on the first Sunday following that day The patch is changed every week for three weeks after a patch free interval of one week again the patch is commenced. (Patch for 3 week and no patch for one week).
It contains 6.00 mg norelgestromin (NGMN) and 0.75 mg ethinyl estradiol (EE). The transdermal patch was designed to deliver EE and NGMN over a seven-day period while oral contraceptives (containing NGM 250 mcg / EE 35 mcg) are administered on a daily basis.
The most common adverse reactions reported during clinical trials were breast symptoms, headache, application site disorder, nausea, dysmenorrhea and abdominal pain. The most common events leading to discontinuation were application site reaction, breast symptoms (including breast discomfort, engorgement and pain), nausea and vomiting, headache and emotional lability.
Since it contains oestrogen and progesterone the usage and limitations are almost similar to that of COC. Contraindications for combined injectable contraceptives are the same as oral [2].
Oestrogen containing preparations (Combined oral contraceptive pills, patches, vaginal ring and combined injectable preparations are not advisable in the following patients:
(a) Women over 35 years who smoke more than 15 cigarettes daily.
(b) Multple risk factors for arterial cardio-vascular disease (obesity, smoking, diabetes, old age and hypertension) BP more than 160/100 and vascular disease. (c) Known thrombogenic mutations (e.g Factor
V Leiden, prothrombin mutation, protein S, Protein C and antithrombin deficiencies) (d) Current history of ischaemic heart disease
and history of cerebrovascular accident. (e) Complicated valvular heart disease
(pulmonary hypertension, risk of atrial fibrillation, history of subacute bacterial endocarditis).
(f) Migraine with aura at any age.
(g) Current breast cancer.
(h) Diabetic Nephropathy / retinopathy/ neuropathy and other vascular disease or diabetes of more than 20 years’ duration. (i) Severe decompensated liver cirrhosis and
Malignant (hepatoma) of the liver.
2.2 Progesterone Only Preparations
2.2.1 Progestogen-only pills (POPs)
POPs contain only a progestogen and no estrogen.
The action of POP is mainly by thickening the cervical mucous and makes the ascent of spermatozoa difficult. Therefore their efficacy is relatively less compared to CHC.
Desogestrel 75 microgram (Cerazette) to be taken daily within 12 hours of interval , where as Etynodiol diacetate 500 microgram (Femulen),
Norethisterone 350 microgram (Micronor) Norethisterone 350 microgram (Nriday) and
Levonorgestrel 30 microgram( Norgeston) should be taken within 4 hours of interval [8].
The desogestrel 75 microgram preparation is as effective as combined pills [9].
Age, obesity and smoking are not factors influencing the prescription. Therefore POP are ideally suitable for elderly obese women who are heavy smokers.
The POP can be started 21 days after the delivery. In the case of miscarriage it can be commenced after 5 days of occurrence.
Women should be advised that changes in bleeding patterns with progestogen-only pill use are common: 2 in 10 women have no bleeding, 4 in 10 women have regular bleeding and 4 in 10 women have irregular bleeding.
There is no evidence of association between progestogen-only pill use and weight change.
2.2.2 Progestin-only injectable contraceptives
Progesterone only injectable include depot medroxyprogesterone acetate (DMPA) and norethisterone enanthate (NET-EN).There are three formulations considered here:
(b) DMPA-SC = 104 mg of DMPA given
subcutaneously. (c) NET-EN = 200 mg of NET-EN given
intramuscularly.
DMPA-SC and, therefore, DMPA-SC should have the same categories as DMPA-IM;
Depo Medroxy progesterone acetate (DMPA 150 mg) has better compliance since 3 monthly intramuscular injection. Suitable for breastfeeding mothers. The disadvantages are weight gain, menstrual irregularities such as irregular bleeding and amenorrhoea, abdominal cramps, discomfort. Fertility can be delayed as long as 10-12 months after last injection...Valvular and complicated congenital heart diseases are not contraindicated for the use of DMPA.
For women under 18 years of age, there are theoretical concerns regarding the hypo-estrogenic effects of DMPA use, including whether these women will achieve their appropriate peak bone mass. DMPA can be continued to age 50 years and then stopped and a suitable alternative contraceptive.
2.2.3 Progestogen-only implants
Progestogen-only implants are a type of long-acting, reversible contraception. The various types of implants that are considered here are the following:
2.2.3.1 Levonorgestrel (LNG)
The LNG-containing implants are Norplant, Jadelle and Sino-implant (II).a. Norplant is a 6-rod implant, each 6-rod containing 36 mg of LNG (no longer in production).
(i) Jadelle is a 2-rod implant, each rod containing 75 mg of LNG.
(ii) Sino-implant (II) is a 2-rod implant, each rod containing 75 mg of LNG. (iii) Etonogestrel (ETG): The ETG-containing
implants are Implanon and Nexplanon. Both consist of a single-rod implant containing 68 mg of ETG.
Norplant is a subcutaneous contraceptive with levonorgestrel and implanon is etonogestrel releasing implant.
Implanon is a progesterone only single rod implant and inserted subdermally in the upper
arm at the inner side of the non-dominant upper arm about 8-10 cm (3-4 inches) above the medial epicondyle of the humerus. The Implanon is a long-acting (up to 3 years) and to be replaced with a new one at the end of 3 years. It is single, off-white, soft, flexible, ethylene vinylacetate (EVA) implant, 4 cm in length and 2 mm in diameter containing 68 mg etonogestre. It releases 60 to 70 mcg/day in first 5 to 6 weeks and decreases to approximately 35 to 45 mcg/day at the end of the first year, to approximately 30 to 40 mcg/day at the end of the second year, and then to approximately 25 to 30 mcg/day at the end of the third year.
It may be used during breastfeeding 4 weeks after delivery.
It is not suitable for women with current or past history of thrombosis or thromboembolic disorders, liver tumors, benign or malignant, or active liver disease, undiagnosed abnormal genital bleeding known or suspected breast cancer and personal history of breast cancer, or other progestin-sensitive cancer, now or in the past [10].
Smokers can use implanon [2].
2.2.4 Progesterone releasing IUCDs
The LNG-IUS has vertical stem containing 52 mg levonorgestrel (LNG) mixed with
polydimethylsiloxane. It releases 20 micrograms LNG per day. It is effective, reversible method of contraception with a failure rate of less than 1 per 100 woman-years. Ideally, the LNG-IUS should be inserted in the first 7 days after the onset of menstruation.
IUCD could be inserted the first 48 h or after 6 weeks due to expulsion rates. Perforation are not increased during postpartum insertion [2].
This is suitable option for women who need contraception and treatment for menorrhagia omen should be informed that the LNG-IUS is licensed for 5 years’ use LNG-IUS can reduce menstrual blood loss by over 90%. Return of fertility following LNG-IUS removal.
The most likely cause of LNG-IUS failure is expulsion. The risk of is around 1 in 20 [11].
Current purulent cervicitis, chlamydia and gonorrhoea infections and pelvic tuberculosis, distortion of uterine cavity due to anomalies or fibroids, endometrial cancer and ovarian cancer contraindicated for the insertion of IUCD. In the event of puerperal sepsis and post septic abortion, the infection must be completely treated before the insertion of the IUCD.
The chances of subsequent ectopic pregnancies are more in women who had ectopic pregnancy. The IUCDs prevent intrauterine pregnancy more than extrauterine pregnancy. Therefore the relative likelihood of ectopic pregnancy is greatly increased.
(a) Women with SLE are at increased risk of ischaemic heart disease, stroke and venous thromboembolism.
(b) Positive (or unknown) antiphospholipid antibodies – LNG IUS to be avoided. (c) Gestational Trophoblastic Disorders – Both
types of IUCD should be avoided.
(d) IUCD should be avoided in active pelvic infection, vaginal bleeding of undiagnosed aetiology, carcinoma of endometrium and cervix.
2.3 Emergency Contraception (EC)
Half of all pregnancies in the United States are unintended [13].
Three types of emergency contraceptions (EC) are available.
These should be taken within 72 hours of sexual exposure.
(a) Levonorgestrel can be given as 0.75 mg one tablet and another 0.75 mg tablet after 12 hours. Studies had shown that single dose of 1.5 mg is equally effective and this dose is convenient [14].
(b) Ulipristal acetate 30 mg single dose is equally effective and well tolerated. This appears to be popular in many countries when ovulation is imminent, UPA is more effective than levonorgestrel [15].
(c) In Yuzpe method an OCP containing ethinyl oestradiol and levonorgestrel are taken. In OCP containing EE 120 microgram and LNG 0.60 mg, altogether 4 tablets to be taken .Two tablets are taken first and 2 tablets to be taken after 12 hours of first dose. When the ECP such as UPA and LNG are not available the Yuzpe method is useful [16].
The levonorgestrel-releasing intrauterine system is currently under evaluation for use as EC. The Copper IUCD could be used as emergency contraception.
Return of fertility occurs within few months with the exception of DMPA (10 months delay) and NET-EN (6 months) from the date of the last injection regardless of the duration of their use.
3. FUTURE HORMONE PREPARATION
MicroCHIPS, an IT start-up company with links to Massachusetts Institute of Technology, is developing a radical new contraceptive - a tiny microchip implanted under the skin that can be operated wirelessly by remote control. Micro CHIPS is a device measuring just 20 x 20 x 7 mm designed to be implanted under the skin of the buttocks, abdomen or upper arm.
When a woman wishes to conceive, she simply turns off the device with a remote. The chip would not need to be removed from the woman until 16 years of use have elapsed. By contrast, current hormonal birth control implants last a maximum of 5 years.
The levonorgestrel is contained on the chip using a hermetic titanium and platinum seal developed by MicroCHIPS. The hormone is released by passing an electric current from an internal battery through the seal, which melts it temporarily, allowing a small dose of levonorgestrel to be released each day. This can be used up to 16 years.
MicroCHIPS, with the backing of Bill Gates, plan to submit the implant for preclinical testing in the US next year, and believe that the device could go on sale by 2018.
The effectiveness of any contraceptive method depends on consistent and correct use. The efficacy vary between the typical and perfect use. With regard to the male condom, the percentage of women experiencing an unintended pregnancy within the first year of use in typical is 15 but in perfect is only 2.
4. CONCLUSION
negative physical and mental health effects for children [16].
More than 200,000 maternal deaths each year are attributable to the failure or lack of contraceptive services. 40% of unintended pregnancies end up in induced abortions Consistent use of contraceptives can avoid unfortunate maternal deaths and unintended pregnancies [17].
Effective contraception benefits both mothers and children by decreasing morbidity and mortality, improving the social and economic status of women, and the relationship of the mother with all her children [18]. Unfortunately the access to birth control remains uneven and unequal.
The availability of a greater number of contraceptive choices will increase the use of more effective methods and thus has the potential to reduce unintended pregnancies and abortions. The caring health worker should decide the suitable contraceptive method considering educational standard, cultural pattern, life style, living condition, financial status.
CONSENT
It is not applicable.
ETHICAL APPROVAL
It is not applicable.
COMPETING INTERESTS
Authors have declared that no competing interests exist.
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© 2016 Najimudeen and Sachchithanantham; This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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