Since the introduction of the first oral contraceptive pill in 1959, a succession of new, improved oral contraceptives has been developed.

Oral contraceptives (OCs) are now the most widely used form of reversible contraception throughout the world. Beyond the obvious benefit of planned pregnancy, contraception is reversible (patients return to normal fertility 11-13 months after stopping the pill).

They allow for programmed menstruation and offer some protection against genital tract infections. They decrease menorrhagia, dysmenorrhoea and premenstrual syndrome, as well as benign breast disease and ovarian cysts.

They improve acne, hirsutism and protect against ovarian, endometrial and colorectal cancer, while assisting in the management of polycystic ovarian syndrome and endometriosis.

Gestodene

Gestodene is a third-generation progestogen with more selective progestogenic activity to improve cycle control. It has a neutral androgenic effect to minimise metabolic changes and adverse effects. This means neutral or positive changes on lipid and glucose profiles and is skin friendly. It is an active progestogen with 100% bioavailability, in contrast to desogestrel and norgestimate which are prodrugs. It has shown better cycle control than levonorgestrel, desogestrel and norgestimate-containing OCs. The adverse effects (AEs) profile is similar to that of levonorgestrel, desogestrel, and norgestimate-containing OCs. The most common AEs are headache and breast tenderness.

Drospirenone

Drospirenone is a novel progestogen with antimineralocorticoid, progestogenic and antiandrogenic activity. It is derived from 17α-spironolactone, an aldosterone antagonist (potent diuretic). It resembles natural progesterone in the way it works.

The antimineralocorticoid (diuretic) effect on renin-aldosterone system reduces bloating and water retention. It has good cycle control, similar to gestodene, desogestrel and levonorgestrel-containing combined OCs (COCs). Drospirenone, cyproterone acetate and dienogest are the only progestogens with antiandrogenic activity at therapeutic doses, which has a beneficial effect on acne, oily skin and hirsutism (included in its indications). It has a beneficial effect on mood and premenstrual syndrome (included in indications). It has AEs similar to those of other COCs – headaches and breast pain being the most common. Unlike other progestogens, drospirenone has potent antimineralocorticoid activity and has the potential to offset fluid retention when used in a combined oral contraceptive. In addition, drospirenone has antiandrogenic properties, which may result in improved skin condition. In terms of weight gain, 30mg ethinylestradiol (EE)/3mg drospirenone was associated with a significantly lower body weight than the EE/desogestrel combination. In addition, women reported an improvement in pre-existing acne and seborrhoea with 30mg EE/3mg drospirenone.

Risks

Venous thromboembolic (VTE) disease:

• Risk of venous/arterial thromboembolism very small but greater than progestogen-only or non-hormonal contraception
• VTE risk is lower than during pregnancy and postpartum period
• Third-generation progestogens have higher VTE risk than second generation
• COC-containing higher EE doses (50µg) are associated with greater risk of VTE than lower EE doses (20 and 30µg)
• COCs contraindicated in women with a history of venous thromboembolic disease.

Arterial thromboembolic disease:

• COCs are associated with a very small increased risk of MI and ischaemic stroke that appears to be greater with higher doses of oestrogen
• Risk of MI and stroke not influenced by type of progestogen
• Risk of MI and ischaemic stroke still extremely uncommon
• COCs should be avoided or strongly cautioned in women with risk factors for arterial disease, such as untreated hypertension, women over 35 who smoke, gross obesity, dyslipidaemia, diabetes, migraine with aura or new-onset migraine
• COCs are contraindicated in women with history of arterial thromboembolic disease.

Cancer:

• COCs are associated with a small increased risk of breast and cervical cancer, which reduces with time after stopping COCs
• COCs are contraindicated in women with breast or endometrial cancer.

Myths about COCs

There is no clear evidence that COCs cause weight gain, long-term reduction in fertility, depression (however you can try a different progestogen) or have an effect on libido.

Drug interactions with COCs

There are interactions with:

• Broad-spectrum antibiotics
• Antiepileptic drugs except sodium valproate, lamotrigine, gabapentin and levetiracetam
• Rifampicin
• Nevirapine and HIV protease inhibitors
• St John’s Wort.

Cycle control and breakthrough bleeding

Breakthrough bleeding is common and improves over the first 3-4 months of use. For bleeding in the first half of the cycle, increase oestrogen. Total breakthrough bleeding would need more oestrogen and progestogen. Bleeding in the second half of cycle indicates that more progestogen is needed.

Conclusion

Choosing a COC is not a one-size-fits-all approach. You need to consider a woman’s age, her health, or any contraindications to COCs. Ask about her contraception history, what has she used before, has she had breakthrough bleeding, or adverse effects? Does she want additional non-contraceptive benefits such as improved skin, reduced bloating, improved PMS, and reduced dysmenorrhoea? Is a COC suitable? Or is she forgetful? Previous contraceptive failure? Affordability is a factor to bear in mind too.

The guiding principles when considering which COC to prescribe for a patient are to choose a formulation that:

• Has the lowest dose of oestrogen and progestogen to provide good cycle control and effective contraception
• Is well tolerated
• Has the best safety profile
• Is affordable
• Offers additional non-contraceptive benefits if desired.

*References available on request.