The bleeding profile was also assessed in the Archer study involving 1,724 women using 0.625 mg CEE and 2.5/5mg PMA and 5/10mg PMA, respectively, in a continuous or sequential regimen. The incidence and mean duration of withdrawal bleeding and spotting were comparable in both groups using sequential therapy. Among women using continuous HRT, the proportion of women without bleeding increased from 52.1% and 56.5% in cycle 2 to 75.1% and 86.6% in cycle 11, while among women using sequential therapy, the proportion increased from 9.6% and 9.9% in cycle 2 to 17.0% and 19.2% in cycle 11 for the lower and higher PMA dose, respectively. Irregular bleeding was more common during the initial cycles of continuous therapy (34.2% and 23.1%) and its incidence decreased during the study to 13% and 5.8% in cycle 11. The incidence of amenorrhea increased with progestogen dose and number of years since menopause.

Treatment

As continuous therapy is associated with less bleeding, this type of treatment is better accepted by patients than sequential therapy. In a study involving 151 women who were allowed to choose any type of therapy after 2 years of continuous or sequential therapy, after several years 46% were still on continuous therapy and only 32% on sequential therapy.

In another study with transdermal use of 50 ug of 17-beta oestradiol and 250 ug of NETA, bleeding started about 2 days after the end of the progestogen phase (13 +/- 2.9 days) and lasted an average of 4 days (4 +/- 2.8 days). In a similar study, bleeding started on an average of 25.74 days of the cycle and lasted 7.33 days. This bleeding was low intensity or only spotting was observed on 77% of all bleeding days. Irregular bleeding was found in 42% of patients , it was of low intensity or only spotting was observed on 87% of all bleeding days. Only 1 case of simple proliferation was found (1.3%). In the Lindgren study, when using sequentially 50 ug of 17-beta oestradiol and 250 ug of NETA, irregular cycles were observed in 11% , regular cycles in 80% , and no bleeding was observed in 9% of all cycles.