Combined oral contraception: nomegestrol/estradiol (Zoely)

Summary

Nomegestrol/estradiol (Zoely) has similar contraceptive efficacy to drospirenone/ethinylestradiol (Yasmin) with similar numbers of days of unscheduled bleeding, fewer days of withdrawal bleeding and significantly more absence of withdrawal bleeding. Acne and weight gain were reported more frequently in women taking nomegestrol/estradiol than in women taking drospirenone/ethinylestradiol (statistical significance not reported).

Key points

Nomegestrol/estradiol (Zoely) is a combined oral contraceptive that received a marketing authorisation for oral contraception in July 2011. It was not marketed in the UK until May 2013. Nomegestrol/estradiol is taken as a 24/4 regimen (24 active tablets containing 2.5 mg nomegestrol and 1.5 mg 17β‑estradiol, followed by 4 inactive tablets) unlike most other combined oral contraceptives, which are taken as 21/7 regimens. It is 1 of 2 combined oral contraceptives that contain synthetic estradiol that is chemically identical to human estradiol; the other is dienogest/estradiol (Qlaira), which is taken as a 26/2 regimen.

This evidence summary is based on 2 randomised, open-label multicentre trials of similar size and design, which were conducted in parallel in different countries (Mansour et al. 2011 [n=2152]; Westhoff et al. 2012 [n=2281]).

Both studies found that, over 13 cycles, there was no statistically significant difference in contraceptive efficacy between nomegestrol/estradiol and drospirenone/ethinylestradiol (Yasmin) in women aged 18–35 years (the primary outcome). In Mansour et al. (2011) the Pearl Index (in‑treatment pregnancies per 100 woman-years of exposure; 1 woman-year equals 13 cycles of 28 days) was estimated to be 0.38 in the nomegestrol/estradiol group and 0.81 in the drospirenone/ethinylestradiol group (p value not reported). In Westhoff et al. (2012) the Pearl Index was 1.27 in the nomegestrol/estradiol group and 1.89 in the drospirenone/ethinylestradiol group (p value not reported). In previous trials assessing the efficacy of new oral contraceptives the Pearl Index has ranged between 0.0 and 2.0.

Unscheduled bleeding or spotting decreased over time in the nomegestrol/estradiol groups. However, it was statistically significantly more common in the nomegestrol/estradiol group than in the drospirenone/ethinylestradiol group in cycles 2–4 and 11 (p<0.05) in Mansour et al. (2011), and in cycles 2–6 (p<0.05) in Westhoff et al. (2012). In both studies, in women who experienced unscheduled bleeding or spotting, the median number of days was similar between the groups, fluctuating between about 2 and 3 days (p values not reported).

Absence of withdrawal bleeding was statistically significantly more common in the nomegestrol/estradiol groups than in the drospirenone/ethinylestradiol groups (p<0.05 in Mansour et al. 2011 and p<0.001 in Westhoff et al. 2012 in all cycles). A progressive increase in the incidence of absence of withdrawal bleeding was seen in the nomegestrol/estradiol group in both studies, ranging from 22 to 31% in cycles 4−12 in Mansour et al. (2011), and from about 18 to 34% in all cycles in Westhoff et al. (2012).

In both studies, in women who experienced withdrawal bleeding or spotting, the median number of days was lower in women taking nomegestrol/estradiol than in women taking drospirenone/ethinylestradiol (3–4 days compared with 5 days). The difference between the groups was statistically significant in Westhoff et al. (2012) (p<0.001 in all cycles); the p value was not reported in Mansour et al. (2011).

In the 2 studies, about 50% of women taking nomegestrol/estradiol experienced adverse events related to the contraceptive, compared with about 37% of women taking drospirenone/ethinylestradiol. The most frequently reported adverse events related to the contraceptive in both studies were acne, irregular withdrawal bleeding and weight gain. These adverse events were more common in the nomegestrol/estradiol groups, although the significance of the differences between the groups was not reported. In both studies adverse events led to about 18% of women stopping nomegestrol/estradiol and 10% of women stopping drospirenone/ethinylestradiol.

A Faculty of Sexual & Reproductive Healthcare statement on the use of nomegestrol/estradiol notes that combined oral contraceptives that have extended regimens (for example, 24/4 or 26/2) or that contain hormones similar to endogenous hormones may appeal to some women. It states that current evidence suggests that nomegestrol/estradiol is acceptable and safe. However, until more data are available the indications and contraindications for nomegestrol/estradiol must be assumed to be the same as for other combined hormonal contraceptives.

The summary of product characteristics for Zoely advises that, because no epidemiological data are currently available for combined oral contraceptives containing estradiol, the warnings of serious adverse events seen with other combined oral contraceptives (such as venous thromboembolism, other circulatory disorders, breast cancer and cervical cancer) are considered applicable to nomegestrol/estradiol.

Localities making formulary decisions about nomegestrol/estradiol will need to take this evidence into account, bearing in mind that user preference is an important factor in contraceptive choice. A reduction in or absence of withdrawal bleeding may be attractive to some women, but seen as a disadvantage to others. Acquisition cost may be another important factor: a 3‑month pack of nomegestrol/estradiol (Zoely) is £16.50, which is in the middle of the range of combined oral contraceptives (£1.80 to £29.25 for a 3‑month supply).

The manufacturer of nomegestrol/estradiol (Zoely, Merck Sharp & Dohme) and the specialists involved in the production of this evidence summary have suggested that nomegestrol/estradiol is likely to be used as a second- or third‑line option in only a small subgroup of women who have found alternative combined hormonal contraceptives unsuitable.

About this evidence summary

'Evidence summaries: new medicines' provide summaries of key evidence for selected new medicines, or for existing medicines with new indications or formulations, that are considered to be of significance to the NHS. The strengths and weaknesses of the relevant evidence are critically reviewed within this summary to provide useful information for those working on the managed entry of new medicines for the NHS, but this summary is not NICE guidance.