title: Endometrial effect of progesterone delivered by vaginal rings in estrogen-treated postmenopausal women.
abstract: OBJECTIVE
  The type of estrogen and progestin as well as their doses, route and regimens of administration may each affect the benefit-risk profile of postmenopausal hormone therapy. The aim of this study was to evaluate the endometrial effect of progesterone released continuously from a vaginal ring, combined with transdermal estradiol in postmenopausal women.
  
  
  METHODS
  Forty-four postmenopausal women participated in a randomized, double-blind, dose-finding study evaluating two hormonal treatments, combining 50 microg/day of estradiol delivered by transdermal patches and either 0.5-g or 1-g progesterone vaginal rings (PVR) given for 12 weeks. The effect on the endometrium was assessed by histology and the detection of the proliferative marker Ki-67. We also measured the serum concentration of estradiol and progesterone, the tissue concentration of progesterone and the immunolocalization of estradiol and progesterone receptors in the endometrium.
  
  
  RESULTS
  Endometrial thickness was increased after both treatments, although endometrial histology appeared atrophic in most biopsies. A circulating dose-response of serum progesterone levels was observed from the first to the 12th week of PVR use. In the high-progesterone-dose group, the scarce presence of Ki-67 and hormone receptors reflected the predominant action of progesterone in endometrial glands and stroma, in parallel with a lower tissue concentration of progesterone in this group.
  
  
  CONCLUSIONS
  The PVR appears to be a promising method of administering natural progesterone to postmenopausal women treated with estrogen. Estradiol levels corrected the menopausal symptoms, as expected, and the presence of atrophic endometrium in the majority of women indicated that both doses of progesterone oppose the stimulatory estradiol effects, although the percentage of proliferative tissue was not negligible in both groups.
authors.affiliation: Instituto Chileno de Medicina Reproductiva, Santiago, Chile.
authors.forename: G
authors.initials: G
authors.lastname: Noé
authors.forename: R
authors.initials: R
authors.lastname: Sitruk-Ware
authors.forename: F
authors.initials: F
authors.lastname: Zegers-Hochschild
authors.forename: B
authors.initials: B
authors.lastname: Variano
authors.forename: J C
authors.initials: JC
authors.lastname: Montero
authors.forename: P
authors.initials: P
authors.lastname: Arriagada
authors.forename: A
authors.initials: A
authors.lastname: Li
authors.forename: F Z
authors.initials: FZ
authors.lastname: Stanczyk
authors.forename: J C
authors.initials: JC
authors.lastname: Felix
authors.forename: D R
authors.initials: DR
authors.lastname: Mishell
authors.forename: H B
authors.initials: HB
authors.lastname: Croxatto
mesh_terms: D000279:Administration, Cutaneous; D003274:Contraceptive Devices, Female; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D016503:Drug Delivery Systems; D004717:Endometrium / Q000187:drug effects*; D004958:Estradiol / Q000008:administration & dosage*; D015914:Estrogen Replacement Therapy / Q000379:methods*; D005260:Female; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause; D011374:Progesterone / Q000008:administration & dosage*; D011372:Progestins / Q000008:administration & dosage*; D016896:Treatment Outcome; D014621:Vagina / Q000187:drug effects; D016387:Women's Health
chemical_list: D011372:Progestins; D011374:Progesterone; D004958:Estradiol