Hormonal contraception in the years 2000- 2005: an update.
Hormonal contraception in the years 2000- 2005: an update. |
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Dr C K Chandy
Department of G U Medicine, Coventry & Warwickshire Hospital, Coventry Teaching Primary Care Trust Coventry, England.
ntroduction:
In recent years, there have been some advances in the field of hormonal contraception. These will enable the couple or individual to control the family according to their lifestyles and also enable the healthcare providers to give the appropriate contraceptives at the right times of their clients' lives. The available choices are modifications of the methods used in the past 3 decades and more research is underway to find the ideal contraceptive method.
The recent developments in hormonal contraception may be discussed as:
a. New Products (Yasmin, Cerazette & Levonelle-2)
b. New routes of administration (Evra Patch, Nuva Ring and Implanon)
New products
(a) Yasmin
Yasmin was marketed in April 2002 and it contains ethinyloestradiol 30mg and drospirenone 3 mg. Drospirenone is a new progestogen derived from _ spiranolactone and has anti-mineralocorticoid and antiandrogenic activity. It is the only progestogen that simulates natural progesterone and it competes with aldosterone receptors thereby blocking the renin-angeotensin –aldosterone system (RAAS) which may be triggered by the oestradiol present in the combined oral contraceptive (COC)1.
Yasmin is an oestrogen dominant pill and its efficacy and side effects are similar to other COCs. There are some reports and studies which raised concerns about increased risk (up to 4 fold) of deep veins thrombosis (DVT). Critical analysis showed that these studies were unreliable and therefore yet to be proven with well conducted studies4. It costs about £5.00 per month (seven times costlier than second generation COC) and hence not readily available in most Community Family Planning Clinics.
Indications
i. COC induced weight problem and hypertension - Yasmin may help to prevent weight gain and development of hypertension by inducing diuresis and thereby decreasing fluid retention.
ii. Polycystic ovarian diseases (PCOD) - An observational study of Yasmin in the management of women with PCOD showed that it is good for cycle control and acne without any beneficial effect on hirsutism after 6 months of therapy2.
iii. Acne - Yasmin has been shown to be as effective as Dianette for women with mild to moderate acne1. It can therefore be used as a substitute for Dianette or for the maintenance therapy after the initial treatment with Dianette.
Contraindications
It should not be used in patients at risk of hyperkalemia (renal and adrenal insufficiency), and hepatic dysfunction 3.
(b) Cerazette
This new progestogen only pill (POP) containing 75 micrograms desogestrel was licensed in the UK at the end of 2002. It inhibits ovulation in about 91-97% of cycles when compared to the lower dose older POPs which inhibits only 50-67% of cycles. It also has an effect on cervical mucus and the endometrium. It is highly efficient, oestrogen free and its androgenic effect is less than those of older POPs. It has no major adverse effect on lipid metabolism or venous thromboembolism. Cerazette is exempted from the 3-hour rule in cases of missed POP pill and has the 12-hour rule similar to COC.
Indications
• Women weighing more than 70 kg.
• It is good for those who need reliable contraception and where oestrogen is contraindicated e.g. young people, woman with previous history of ectopic pregnancy, chronic intercurrent diseases, menstrual symptoms like dysmenorrhoea, menorrhagia, pre-menstrual tension, functional ovarian cysts, mid-cycle ovulation pain or poor tolerance to COC pills.
• Trial of Cerazette for 3 months prior to Implanon insertion although this is not evidence based.
The main disadvantages of Cerazette are cycle changes similar to other POPs and amenorrhoea is more common with prolonged use. Cerazette is reasonably priced (3 – 5 times expensive than other POPs, twice the cost of Microgynon and 50% more expensive than Femodene).
c) Levonelle-2
This is the first progestogen only emergency contraception (POEC) licensed in the UK in 1999. It consists of 2 pills each containing 750_gm levomorgestrel. Recently there is an increase in the use of POEC due to various reasons. In 2001 its status changed from prescriptions only medicine (Leveronell-2) to over-the-counter medicine (Levonelle). As a consequence of its safety, plans are in progress to market it as an over counter product. This will increase the availability of POEC and hopefully decrease the rate of unplanned pregnancies.
A recent large randomised control trial showed that the risk of vomiting with POEC is low at 1% and delay of next menses more than 1 week occurs only in 5% of cases5. A single dose of 1.5mg is equally effective compared to the divided dose of 12-16 hours apart and this should increase compliance. In the UK licence for single dose was obtained in October 2003, and there is evidence that the efficiency of POEC is less likely to be adversely affected adversely with the extended use up to 120 hours. The effect of enzyme inducers on POEC is uncertain and the current advice is to take 1.5mg stat. followed by 750_gm after 12 hours6. Recently there are concerns, but not yet proven about the association of POEC and ectopic pregnancy. Although the risk is very small, it is prudent to discuss this issue and advise the client to seek medical advice in cases of abdominal pain with abnormal periods after POEC7.
New routes of administration
Evra Patch and Nuva Ring are the new non-orally administrated combined oestrogen and progestrogen contraceptive with efficiency similar to COC as they inhibit ovulation.
Implanon is a progestogen only contraception administered subdermally into the lower surface of the upper non-dominant arm between biceps and triceps.
Evra Patch
Evra, the first contraceptive skin patch (4.5cm x 4.5cm) became available in the UK in 2003. It is 99% effective when used correctly and offers the convenience of once-a-week dosing. It contains 600_mg of ethynyl oestradiol and 6mg of norelgestromine and releases 20mg and 150mg respectively into the systemic circulation each day. Norelgestromine is the active metabolite of norgestimate, the progestogen resent in the combined pill Cilest. After application the peak serum concentration of hormones reaches by around 48 hours and maintain sufficient level to suppress ovulation for another 7 days8. Evra is a smooth thin, beige coloured patch worn discreetly underneath a woman’s clothes on the abdomen, back, upper arms and buttocks but avoiding the breasts. Swimming, bathing and exercising are not contraindicated. It is a weekly patch replaced on the same day of the week for 3 weeks followed by one patch-free week.
a) Advantages of Evra Patch and Nuva Ring over COC
• Avoids daily and hence better compliance. (Currently a weekly reminder call by the company is available to those who are registered with them)
• Avoid the first pass effect in the liver and therefore required only smaller doses to achieve contraceptive efficiency and good cycle control. This might also reduce effects on clotting factors, but the risk of venous thrombo-embolism is currently unknown.
• Avoids using extra precaution, as efficiency is not reduced by vomiting and severe diarrhoea or by using any broad-spectrum antibiotic.
• Avoids high peak concentration as hormones are released steadily and continuously.
• Avoids GI upset induced by COC.
Advantages over injectable, IUD/IUS and Implanon
• Good cycle control
• Avoid involvement of health professional for injection, insertion or a minor surgical procedure.
Disadvantages and side effects
a) Cycle control
• Withdrawal bleeding last 5-6 days (a day later and longer than COC8).
• Breakthrough spotting, (not bleeding) was more common in the patch users in the first 2 cycles and only about 10% of users had breakthrough bleeding or spotting in the 3rd cycle8. Breakthrough bleeding may occur in about 30% of COC users especially in the first few cycles.
• Only 0.1% patch users and 0.2% of COC users experienced amenorrhoea8.
b) Breast tenderness: about 20% experience breast tenderness especially in the first 2 cycles but only 2% withdrew from the studies because of this reason.
c) Application site reactions: another 20% experienced application site reaction but again 2% discontinued the method due to this reason. In order to minimise this reaction it is advisable to change the position of the patch each time.
d) Detachment: about 5% of the patch had to be replaced, 2% due to complete detachment and 3% due to partial detachment. Hormone delivery may be affected by partial or complete detachment.
The management of patch detachment8:
- if <24 hours of reapply or replace
detachment immediately without
any extra precaution
- if a) >24 hours of start a new patch
detachment cycle with extra precautions for 7 days
- if unsure of patch and emergency
detachment contraception if
indicated.
- if replacement
delayed >48
hours during
week 2 or 3
e) Patch disposal:
Majority of hormones (80%) remains in the patch after 7 days of use8. It is therefore not advised to flush the used patch through the toilet to prevent water pollution, instead discard it according to the local requirement or return it to the pharmacy.
f) It may be visible.
Special Circumstances
i) Obesity – Simultaneous use of barrier method is advised as efficiency may be reduced in women who weigh more than 90kgs.
ii) Drug interactions – Extra precaution is required during and for 28 days after stopping the enzyme inducing drugs. HIV positive women should be advised to change to a long acting injectable progestogen or another form of contraceptive if antiretroviral therapy commences6. This precaution is not necessary with broad-spectrum antibiotic use, as transdermal use bypasses the enterohepatic circulation.
Cost: When compared to COC containing 20mg ethimylestradiol, these are, Evra: £100, Mercilon £35 and Loestrin 20 is £20 per annum.
Nuva Ring
The Nuva Ring delivers combined contraceptive hormones (ethinylestradiol 15mg and etonogestrel 120 mg per day) transvaginally over a period of three weeks followed by one week ring free interval. It is now licensed in the USA and most of Europe, but will be available in the UK in 2005. It is made of ethylene vinyl acetate (EVA) co-polymer with 54mm and 4mm outer and cross sectional diameter respectively9. It is a transparent and flexible ring packed in a sealed re-closable aluminium sachet with a zipper1. This will protect the ring from light and moisture and allow it to be replaced in the sachet for disposal after use.
Advantages
• All the advantages of non-oral route mentioned above.
• A reliable, well-tolerated and acceptable method of contraception.
• Easy to insert and remove by women themselves and the instructions are also easy to follow.
• Good cycle control – withdrawal bleeding that occurs during the ring free period is superior to those associated with the oral contraceptive which may be due to the steady blood levels of hormones. Breakthrough bleeding mostly spotting occurs in less than 6% of cycles even in the initial months of use.
• Efficiency and safety of the ring is unlikely to be affected by vaginally administered antimycotics and spermicides1.
• Fertility is rapidly returned within the first month of removal and no significant changes observed in blood pressure, weight or metabolic parameters.
• Tricycling or avoiding withdrawal bleeding during holidays can be achieved by replacing a new ring every 3 weeks.
• The ring can be removed for intercourse if desired for up to 3 hours1. If it remains outside for more than 3 hours, re-insert as soon as possible and additional precautions should be used until the ring has been used continuously for 7 days. Emergency contraception is required if indicated during this period.
Disadvantages
• Non-specific vaginitis is the most common side effects occurring in 6% of women but only 1% withdrew from the studies for this reason1.
• Interference with intercourse – about 15% of women and 1/3 of partners occasionally felt the ring during sexual intercourse, but less than 10% objected to its use1. As mentioned above, the ring can be removed for intercourse if desired but must be re-fitted within 3 hours.
Implanon
Implanon consists of a single flexible rod containing 68mg of etonogestrel (biologically active metabolite of desogestrel) releasing steadily on an average between 30-40_gm per day over a period of 3 years. It is highly effective (pearl index almost zero), long acting (3 years) and reversible (ovulation within 6 weeks) method of contraception with all the benefits of non oral route. It was launched in 1999 and has gained popularity world-wide (2 million users) and in the UK more than 40,000 women each year4. Implanon inhibits ovulation mainly by inhibiting L H surge and FSH and oestradiol levels are either minimally reduced or unaffected10. Therefore there are no concerns about bone minimal densities in cases of prolonged amenorrhoea unlike Depo-provera users.
of 3 years. It is highly effective (pearl index almost zero), long acting (3 years) and reversible (ovulation within 6 weeks) method of contraception with all the benefits of non oral route. It was launched in 1999 and has gained popularity world-wide (2 million users) and in the UK more than 40,000 women each year4. Implanon inhibits ovulation mainly by inhibiting L H surge and FSH and oestradiol levels are either minimally reduced or unaffected10. Therefore there are no concerns about bone minimal densities in cases of prolonged amenorrhoea unlike Depo-provera users.
As with other progestogen only contraceptives its common side effects include cycle changes especially in the first 3 – 4 months, mood swings and weight gain and other minor nuisance side effects encountered with any other hormonal contraceptions. Cyclical Mercilon or Marvelon for 2 months may be tried to control the menstrual problems.
Implanon is indicated in all people in whom oestrogen is contraindicated. Implanon can be used without additional contraception for those who are obese. If the obese user remains amenorrhoeic, replacement of Implanon will be as usual, at the end of 3 years, and if not, replacement after 2 years or use of additional contraception is a wiser option. This is because blood levels of etonogestrel are lower in women with BMI greater than 35kg/m2.
Women on enzyme inducers may experience breakthrough bleeding and the contraception efficiency is reduced, and this has resulted in few Implanon failures. Hence it is advisable to discuss the options of changing the contraceptive method to injection Depo-Provera or Mirena if there are no contraindications.
Implanon insertions and removals require training. As a consequence of its cost (£90), it may be a good clinical practice to give a trial of Cerazette for 3 months prior to the insertion of Implanon.
References:
1. Wilkinson C and Szarewski A. Contraceptive Dilemmas; 1st edition 2003
2. Manisha Palep-Singh et al. An observational study of Yasmin in the management of women with PCOD; Journal of FFP & RHC 2004; 30(3) 163-165.
3. Guillebaud J. A brief - Margaret Pyke Centre (MPC); Update on Contraception 2002
4. Mansour D. An update on contraception (excluding Transdermal Therapies). Journal of the National Association of Nurses for Contraception and Sexual Health. Summer 2004; (44): 16-18.
5. Ali Kubba. Contraception update. Journal of the National Association of Nurses for Contraception and Sexual Health; Summer 2004; No. 44; 16-18
6. Mitchell HS, Stephens ES. Contraception choice for HIV positive women. Sex Transmitted Infection 2004; (80): 167-173.
7. Black K, Ali Kubba. Is there a link between ectopic pregnancy and Progestogen-Only Emergency Contraception? Trends in Urology Gynaecology and Sexual Health. Editorial, May/June 2003.
8. Evra – a patch on oral contraception. Drug and Therapeutic Bulletin 2003; (41): 89-91.
9. Black K, Ali Kubba. What’s new in contraception? Trends in Urology Gynaecology and Sexual Health; Jan/Feb 2004; 22-24
10. Wylie A.H.M, Gebbie AE.; Impact of contraception on subsequent fertility. The Obstetrician & Gynaecologist 2002 Vol. 4 (3):151-155
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