In the last several years there has been an influx onto the market of several types of new third generation combined oral contraceptives (COCs). These novel COCs have a slightly different side-effect profile compared to the older COCs (which date back to the 1970s or even earlier). They also can cost up to almost four-fold more. However, are the catchy, modern and typically female names and the fact that these pills are different enough justification for the average woman to pay the extra money? We GPs are clearly responsible if we do not offer our female patients the cheaper alternative, unless there are medical indications to the contrary. Surely it is the patient’s right to be informed and to choose?
One type of newer third generation COC (Yaz®)1 has a reduced pill-free period of four days only, which is a particular advantage for women who may be unreliable remembering to take the pill (as contraception is more secure by the shorter pill-free interval), and for those who have endometriosis. However, these advantages may also be reproduced in many other pill types by running active tablets together and missing the pill-free interval completely in order to reduce the number of periods. There is a higher risk of break-through bleeding in the first few months initially with many pill types, and especially if the woman is taking a low dose COC2 (but this risk is significantly less with the third generation COCs Zoley® and Qlaira®)2. It should be noted that Yaz® and other third generation COCs are much more expensive than the older second generation COCs.
The third generation progestogens nomegestrol acetate, desogestrel, dienogest and the second generation norethisterone have a stronger anti-proliferative effect on the uterine lining than other progestogen types.2, 4 This may result in lighter and eventually, often absent periods, over many months to years, especially if there is a reduced or absent active pill-free interval.2 This may be an advantage for women who have heavy periods and especially for women who have endometriosis or polycystic ovarian syndrome who may be at increased risk of hyper-proliferation of the uterine lining. For other women, though, there may be a significantly increased risk of break-through bleeding over time due to atrophy of the uterine lining, especially for the COCs containing nomegestrol acetate (Zoley®) and desogestrel (Qlaira®).2 This is because the oestrogen in both Zoley® and Qlaira® is oestradiol, and this is less uterine-proliferative than ethinyl-oestradiol6 (the other component of the older COCs containing norethisterone acetate, e.g. Brevinor®). The complete absence of periods may also concern some women, as they may worry about being pregnant.
In the last two decades ethinyl oestradiol 20mg combined with levonorgestrel 75mg or 100mg has become very commonly used, largely replacing the older, previously lowest dose COCs (Triphasil®, Triquilar®). Break-through bleeding is quite common with the newer low-dose oral contraceptives. The risk is increased for any COC if the first cycle is not commenced with an active on the first day of bleeding. Many women will find break-through bleeding settles over a couple of cycles, but it may be enough, however, to put many women off the lowest dose COCs. The advantage, especially for women with a Health Care Card, of this newer low-dose COC is that one type, Femme-tab® ED (20/100), is listed on the PBS, however, it is still generally quite cheap on a private script, especially compared to the latest COCs. The other advantage is that it has much less risk of thrombosis compared to the highest oestrogen dose older COCs and some third generation COCs.2,3
Several brands of the middle strength of COC (oestradiol 30mg, levonorgestrel 150mg) are also significantly cheaper than the new third generation COCs. Compared to the low dose COC, these pills allow more time before a pill is defined as “missed” (twelve hours as opposed to six), have less incidence of break-through bleeding initially and if active pills are used continuously7 and are a good, cost-effective alternative to low dose COCs.
Norethisterone and cyproterone acetate are both often combined with a higher ethinyl oestradiol dosage (35mg) in the older pills and this higher oestrogen dose may be a safety disadvantage for women who in their thirties onwards, especially regarding thromboembolism and cardiovascular disease.2,3 These women should be prescribed the lowest oestrogen dose pill tolerated or alternative contraception as a first-line method, to reduce the risk of clotting disorders and cardiovascular events. The higher dose COCs are useful in women who are taking medications that increase the metabolism of the COC and that could increase the risk of pregnancy, most commonly carbamazepine, phenytoin, rifampicin and certain HIV medications.8 It should be noted that finding the right COC pill for an individual may be a matter of trialling several different types.
In summary, the older COCs are very cost-effective, have a good safety profile and are available in low dose. They are not inferior in efficacy to the newer third generation COCs and should be offered as part of the discussion about which oral contraceptive pill is best for each individual woman to take.
1. Bayer Resources product information http://www.bayerresources.com.au/resources/uploads/PI/file10613.pdf
2. Dr Mary Stewart, Dr Betty Chaar & Dr Deborah Bateson, ‘Combined Oral Contraceptives’, Family Planning NSW
3. RANZCOG, ‘Venous Thromboembolism and Hormonal Contraception’
4. Kristen Page Wright & Julia V Johnson, ‘Evaluation of extended and continuous use of oral contraceptives’, Therapeutics and Clinical Risk Management, 2008
5. Anne Burke, ‘Nomesgestrol acetate-17b-estradiol for oral contraception’, Patient Preference and Adherence, 2013
6. Helgason, S., Damber, MG., von Schoultz, B. & Stigbrand, T. ‘Estrogenic potency of oral replacement therapy estimated by the induction of pregnancy zone protein’, 1982
7. Mary Stewart & Kirsten Black ‘ Choosing a combined oral contraceptive pill’, Australian Prescriber, 2015
8. Back, DJ & Orme, ML ‘Pharmacokinetic drug interactions with oral contraceptives’, 1990