title: Treatment of menopausal symptoms with three low-dose continuous sequential 17β-estradiol/progesterone parenteral monthly formulations using novel non-polymeric microsphere technology.
abstract: OBJECTIVE
  To analyze the short-term efficacy and safety over menopausal symptoms of three low-dose continuous sequential 17β-estradiol (E)/progesterone (P) parental monthly formulations using novel non-polymeric microspheres.
  
  
  METHODS
  This was a multicenter, randomized, single blinded study in which peri- and postmenopausal women were assigned to receive a monthly intramuscular injection of 0.5 mg E + 15 mg P (Group A, n = 34), 1 mg E + 20 mg P (Group B, n = 24) or 1 mg E + 30 mg P (Group C, n = 26) for 6 months. Primary efficacy endpoints included mean change in the frequency and severity of hot flushes and the effect over urogenital atrophy symptoms at 3 and 6 months. Safety variables included changes in the rate of amenorrhea, endometrial thickness and histopathology, and local and systemic adverse events.
  
  
  RESULTS
  Compared to baseline at month 6, the three treatment schemes significantly decreased the rate of urogenital atrophy symptoms and the frequency (mean number per day) and severity (mean number graded as moderate and severe per month) of hot flushes. No differences in studied efficacy parameters were observed between studied groups at baseline or at the end of the study. For all groups the most frequent adverse event was pain at the injection site; however they were all rated as mild. At the end of the study peri- and postmenopausal women displayed no significant changes in endometrial thickness or histopathology in all treated groups. The rate of amenorrhea at the end of the study decreased for all studied groups yet was less evident among postmenopausal women as compared to perimenopausal ones.
  
  
  CONCLUSIONS
  The three low-dose continuous sequential intramuscular monthly treatments of E/P using novel microsphere technology were effective at reducing menopausal symptoms at short-term with a low rate of adverse events. More long-term and comparative research is warranted to support our positive findings.
authors.affiliation: a Instituto Nacional de Perinatología "Isidro Espinosa de los Reyes" , Mexico City , Mexico .
authors.forename: Manuel
authors.initials: M
authors.lastname: Cortés-Bonilla
authors.forename: Roberto
authors.initials: R
authors.lastname: Bernardo-Escudero
authors.forename: Rosalba
authors.initials: R
authors.lastname: Alonso-Campero
authors.forename: María T
authors.initials: MT
authors.lastname: Francisco-Doce
authors.forename: Marcelino
authors.initials: M
authors.lastname: Hernández-Valencia
authors.forename: Cuauhtémoc
authors.initials: C
authors.lastname: Celis-González
authors.forename: Ricardo
authors.initials: R
authors.lastname: Márquez-Oñate
authors.forename: Peter
authors.initials: P
authors.lastname: Chedraui
authors.forename: Juan A
authors.initials: JA
authors.lastname: Uribe
mesh_terms: D000328:Adult; D001284:Atrophy / Q000188:drug therapy / Q000473:pathology; D004958:Estradiol / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D015914:Estrogen Replacement Therapy / Q000009:adverse effects / Q000379:methods; D005260:Female; D052776:Female Urogenital Diseases / Q000188:drug therapy* / Q000473:pathology; D020249:Hormone Replacement Therapy / Q000009:adverse effects / Q000379:methods*; D019584:Hot Flashes / Q000188:drug therapy*; D006801:Humans; D007273:Injections, Intramuscular; D008593:Menopause; D008863:Microspheres; D008875:Middle Aged; D011374:Progesterone / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D016037:Single-Blind Method; D016896:Treatment Outcome
chemical_list: D011374:Progesterone; D004958:Estradiol
keywords: Hormonal therapy; injectable estradiol; menopause; microspheres; progesterone; vasomotor symptoms