Bleeding patterns during continuous estradiol with different sequential progestogens therapy.
OBJECTIVE
: To evaluate the effects on monthly bleeding of four different progestogens administered in association with transdermal estradiol in a continuous sequential estrogen-progestin therapy (CS-EPT).


METHODS
: This prospective, open, randomized, clinical trial included 100 healthy postmenopausal women. Patients were randomized into four treatment groups, each consisting of 25 women. Treatment consisted of 50 mug/day transdermal 17beta-estradiol for all women combined to receive four different progestogens (group A: medroxyprogesterone acetate, 10 mg/day; group B: nomegestrol acetate, 5 mg/day; group C: dydrogesterone, 10 mg/day; group D: micronized progesterone, 200 mg/day) per os from the 14th to 25th day of each 28-day cycle. The duration of treatment was 12 cycles. Patients were asked to record in a daily diary the occurrence of any vaginal bleeding, the days of application of each patch, the days of assumption of the different progestogens, and the exact moment of bleeding onset.


RESULTS
: A total of 937 cycles could be evaluated. In 690 cycles (73.6%), regular progestogen-related bleeding was reported. Among the other cycles, we observed 73 episodes of amenorrhea (7.8%, each one lasting one cycle), 78 episodes of irregular bleeding (8.3%), and 96 episodes of spotting (10.2%). Patients receiving nomegestrol acetate had a significantly higher incidence of regular progestogen-associated bleeding in comparison with those receiving medroxyprogesterone acetate or natural progesterone, and patients receiving dydrogesterone had a significantly higher incidence of regular progestogen-associated bleeding in comparison with those receiving natural progesterone.


CONCLUSIONS
: Our data suggest that CS-EPT generally leads to regular withdrawal bleeding in women without uterine pathology. Micronized progesterone seems to induce more irregular bleeding episodes.
Di Carlo
Costantino
C
Department of Gynecology and Obstetrics, and Pathophysiology of Human Reproduction, University of Naples Federico II, Naples, Italy.
Sammartino
Annalidia
A
Di Spiezio Sardo
Attilio
A
Tommaselli
Giovanni A
GA
Guida
Maurizio
M
Mandato
Vincenzo D
VD
D'Elia
Antonio
A
Nappi
Carmine
C
D000279:Administration, Cutaneous; D000568:Amenorrhea / Q000453:epidemiology; D003271:Contraceptive Agents, Female / Q000627:therapeutic use; D004394:Dydrogesterone / Q000627:therapeutic use; D004717:Endometrium / Q000000981:diagnostic imaging; D004958:Estradiol / Q000627:therapeutic use; D015914:Estrogen Replacement Therapy / Q000379:methods*; D005260:Female; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000627:therapeutic use; D008535:Megestrol / Q000627:therapeutic use; D008875:Middle Aged; D009649:Norpregnadienes / Q000627:therapeutic use; D017698:Postmenopause; D011374:Progesterone / Q000627:therapeutic use; D011446:Prospective Studies; D014463:Ultrasonography; D014592:Uterine Hemorrhage / Q000139:chemically induced*
D003271:Contraceptive Agents, Female; D009649:Norpregnadienes; D011374:Progesterone; D004958:Estradiol; C038501:nomegestrol acetate; D004394:Dydrogesterone; D017258:Medroxyprogesterone Acetate; D008535:Megestrol