Since the introduction of the first combined hormonal contraceptive in 1960, there have been many developments toward the goal of minimizing side effects and improving compliance without compromising efficacy. The first of these advancements was a decrease in hormone concentrations to the currently used low-dose formulations. Oral contraceptives (OCs) combining a progestin with ≤ 35 mcg ethinyl-estradiol (EE) are now standard, with the exception of select circumstances such as in women using antiepileptic drugs. Formulations with EE 20 mcg have further been shown to decrease estrogenic effects such as bloating and breast tenderness without compromising efficacy.
Subsequent development of newer-generation progestins resulted in stronger progestogenic activity and decreased androgenic effects such as acne, hirsutism and lipid changes, as well as other unwanted estrogenic effects such as nausea and fluid retention. The latest development in combined OCs (COCs) has been in incorporating more physiological forms of estrogen with a progestin. Non oral delivery methods represent another recent advancement in combined hormonal contraception, including the contraceptive vaginal ring, the transdermal contraceptive patch and monthly injections of estrogen plus progestogens. Despite these advances, issues remain associated with the use of combined hormonal contraceptives. There was a very interesting attempt to examine available combined hormonal contraceptive options and compare them, where data are available, for efficacy, safety, cycle control, adverse events profiles and associated risks, and user preference and satisfaction. Particular areas of interest, including bone mineral density, venous thrombosis and use of antiepileptic drugs were also examined.
Contraceptive efficacy is often calculated in clinical trials using the Pearl Index (PI), which is used as an estimation of the number of unintended pregnancies in 100 woman-years. Head-to-head trials, where methodology is constant for all treatments, have shown that most combined contraceptive products are similarly efficacious. For example, among 983 women randomized to either the contraceptive vaginal ring (etonogestrel120 mcg/ EE 15 mcg) or a COC containing drospirenone (DRSP) 3 mg and EE 30 mcg, one in-treatment pregnancy occurred in the ring group, and four occurred in the COC group. A similar study comparing the vaginal ring containing etonogestrel 120 mcg/ EE 15 mcg with a COC containing LNG 150 mcg/ EE30 mcg reported five in-treatment pregnancies in each intent to-treat population.
The relative frequency and duration of unexpected bleeding associated with various methods are important to understand, as several studies have shown that irregular and unexpected bleeding episodes are often reasons for discontinuation of contraceptive use. Androgenic effects of combined hormonal contraceptives associated with progestins include acne, hirsutism and lipid changes. The total androgenic effect is dependent on the type of progestin and level of estrogen. There are several types of progestins that can be subdivided according to their molecular structure. Estranes and gonanes are derived from nortestosterone and consist of norethindrone, ethynodioldiacetate, lynestrenol, norethynodrel, LNG, DSG, GES, NMG and dienogest. Some of the newer testosterone derived progestins, which include DSG, gestodine and NMG, are reported to have lesser androgenic effects than their predecessors. Etonogestrel, the progestin used in the vaginal ring, is the active metabolite of DSG. Norelgestromin, the progestin used in the transdermal patch, is the active metabolite of NMG.
Hormonal contraceptives have also been reported to affect sexual function. A prospective study of 80 women aged 19–31 years reported that oral DRSP 3 mg/ EE 30 mcg increased sexual enjoyment and satisfaction, orgasm frequency, arousal and frequency of sexual activity. In a controlled study comparing a COC containing DSG 150 mcg/ EE 20 mcg with the vaginal ring, both groups reported improvements in assessed sexuality parameters compared with the control group; however, only the vaginal ring was associated with an increase in sexual fantasy.
The effect of combined hormonal contraception on bone mineral density (BMD) in all patients (adults and adolescents) is not as clear. While there is some evidence that combined hormonal contraception may exert negative effects on bone, most studies have shown that combined hormonal contraceptives are associated with improved or neutral changes in BMD. A recent systematic review of 13 randomized controlled trials found that combination contraceptives do not appear to affect bone health. In another systematic review of 13 studies, nine studies showed a positive association between low-dose COCs and BMD, and four studies did not; however, no studies showed a negative association.
One of the more recent developments in contraceptives has been the successful introduction of E2 into COCs. Previous attempts to include E2 as the estrogenic component of COCs were unsuccessful because of irregular bleeding and unacceptable cycle control.
Development of newer contraceptives has progressed with the goal of reducing unwanted side effects while maintaining efficacy. The introduction of physiologic estrogen into COCs is the most recent development in this area. Alternative delivery methods, including the transdermal patch and vaginal ring, have provided additional options for combined hormonal contraception. No hormonal contraceptive, however, is without risks. Choosing the most appropriate hormonal contraceptive should be individualized according to a woman’s risk profile, age, concomitant medications and preference. Health care providers are encouraged to counsel patients regarding available contraceptive options and their associated benefits and risks.