Spacing-out of progestin - efficacy, tolerability and compliance of two regimens for hormonal replacement in the late postmenopause

Abstract

Estrogen replacement therapy with sequential progestin at greater than monthly intervals has been frequently used in practice to reduce progestational side-effects and bleeding episodes, but clinical trials are still lacking. Two new regimens were tested. The main objective was to evaluate efficacy, predominantly in urogenital complaints, tolerability, and patient acceptance. Transdermal estradiol (0.05 mg/day) and norethisterone acetate orally (2.5 mg/day) were administered for 12 days every 2 or 3 months (group A, n = 83, group B, n = 89) to patients whose menopause had begun at least 4 years earlier. Study duration was three long cycles in each group within 7-10 months. Efficacy was good [group A/B = 94/92%], as was systemic tolerability [95/97%]; major skin reactions occurred in 7 and 4%, respectively. Patients' acceptance for continuation of spaced-out treatment was 88 and 87%, respectively. Progestin-associated withdrawal bleedings occurred in 66 (61%) of patients; mean duration 4.3 +/- 1.9/4.8 +/- 1.6 days, with no significant changes during therapy; intensity decreased during therapy. Breakthrough bleeding which required sonographic or histological work-up occurred in 8 and 13%, respectively. Despite the low dosage, transdermal estradiol proved to be efficacious in urogenital complaints. The high acceptance and the reduction of the overall progestin dose to avoid side-effects are of particular prognostic importance with regard to the prevention of cardiovascular diseases. Transdermal estradiol combined with 2- or 3-monthly progestin may be a valid regimen in the late post-menopause, but further studies using spacing-out regimens are urgently needed.

Hormone therapy after endometrial cancer.

“…With long-cycle (spacing out) therapy, an increased risk cannot be excluded (Bjarnason et al 1999), although we and others did not observe this (Rabe et al 1997, Erkkola et al 2002 (evidence level II-1). However, increased risk has also been demonstrated with addition of monthly sequential progestogen (SCEPT), in contrast to CCEPT (Weiderpass et al 1999, Hill et al 2000 (evidence level II-2).…”

Hormone Therapy after Endometrial Cancer

“…It is well recognised that the primary risk for an ECa can be reduced through a combination with progestogen every cycle for a minimum of 10, or even better, 12 to 14 days [12]. With long-cycle (spacing out) therapy an increased risk cannot be excluded [13] although we and other authors did not observe this [14,15]. However, an increased risk has also been demonstrated with monthly sequential progestogen addition (SCEPT) in contrast to CCEPT (Table 1) [16,17].…”

Vaginal Hormone Therapy for Urogenital and Menopausal Symptoms

“…Preliminary data with quarterly norethindrone acetate, 2.5 mg for 12 days, showed that 61% experienced a withdrawal bleeding that lasted a mean of 4.8 AE 1.6 days in women using 50-mg estradiol patches. 141 Withdrawal bleeding averaged one half day less when the progestin was given every other month. Hirvonen et al 142 gave more than 200 women an average of 1 mg of estradiol transdermal gel daily opposed by 10 mg of oral medroxyprogesterone acetate (MPA) for 12 days every 28-or 84-day cycle.…”