title: Menopausal symptoms and treatment-related effects of estrogen and progestin in the Women's Health Initiative.
abstract: OBJECTIVE
  To estimate the effects of estrogen plus progestin (E+P) therapy on menopausal symptoms, vaginal bleeding, gynecologic surgery rates, and treatment-related adverse effects in postmenopausal women.
  
  
  METHODS
  Randomized, double-blind, placebo-controlled trial of 16,608 postmenopausal women, ages 50-79 (mean +/- standard deviation 63.3 +/- 7.1) years, with intact uterus, randomized to one tablet per day containing 0.625 mg conjugated equine estrogens plus 2.5 mg medroxyprogesterone acetate (n = 8,506) or placebo (n = 8,102), and followed for a mean of 5.6 years. Change in symptoms and treatment-related effects were analyzed at year 1 in all participants. Bleeding and gynecologic surgery rates were analyzed through study close-out.
  
  
  RESULTS
  Baseline symptoms did not differ between the treatment groups. More women assigned to E+P than placebo reported relief of hot flushes (85.7% versus 57.7%, respectively; odds ratio 4.40; 95% confidence interval 3.40-5.71), night sweats (77.6% versus 57.4%; 2.58; 2.04-3.26), vaginal or genital dryness (74.1% versus 54.6%; 2.40; 1.90-3.02), joint pain or stiffness (47.1% versus 38.4%; 1.43; 1.24-1.64), and general aches or pains (49.3% versus 43.7%; 1.25; 1.08-1.44). Women asymptomatic at baseline who were assigned to E+P more often developed breast tenderness (9.3% versus 2.4%, respectively; 4.26; 3.59-5.04), vaginal or genital discharge (4.1% versus 1.0%; 4.47; 3.44-5.81), vaginal or genital irritation (4.2% versus 2.8%; 1.52; 1.27-1.81), and headaches (5.8% versus 4.7%; 1.26; 1.08-1.46) than women on placebo. Estrogen plus progestin treatment prevented the onset of new musculoskeletal symptoms. Vaginal bleeding was reported by 51% of women on E+P and 5% of women on placebo at 6 months; most bleeding was reported as spotting. Gynecologic surgeries (hysterectomy and dilation and curettage) were performed more frequently in women assigned to E+P (3.1% versus 2.5% for hysterectomy, hazard ratio = 1.23, P = .026; 5.4% versus 2.4% for dilation and curettage, hazard ratio = 2.23, P < .001).
  
  
  CONCLUSIONS
  Estrogen plus progestin relieved some menopausal symptoms, such as vasomotor symptoms and vaginal or genital dryness, but contributed to treatment-related effects, such as bleeding, breast tenderness, and an increased likelihood of gynecologic surgery.
authors.affiliation: Department of Obstetrics and Gynecology, Medical College of Wisconsin, 9200 West Wisconsin Avenue, Milwaukee, WI 53226, USA. barnabei@mcw.edu
authors.forename: Vanessa M
authors.initials: VM
authors.lastname: Barnabei
authors.forename: Barbara B
authors.initials: BB
authors.lastname: Cochrane
authors.forename: Aaron K
authors.initials: AK
authors.lastname: Aragaki
authors.forename: Ingrid
authors.initials: I
authors.lastname: Nygaard
authors.forename: R Stan
authors.initials: RS
authors.lastname: Williams
authors.forename: Peter G
authors.initials: PG
authors.lastname: McGovern
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Young
authors.forename: Ellen C
authors.initials: EC
authors.lastname: Wells
authors.forename: Mary Jo
authors.initials: MJ
authors.lastname: O'Sullivan
authors.forename: Bertha
authors.initials: B
authors.lastname: Chen
authors.forename: Robert
authors.initials: R
authors.lastname: Schenken
authors.forename: Susan R
authors.initials: SR
authors.lastname: Johnson
mesh_terms: D000284:Administration, Oral; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004966:Estrogens, Conjugated (USP) / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D020249:Hormone Replacement Therapy / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D017698:Postmenopause / Q000187:drug effects* / Q000502:physiology; D011336:Probability; D011788:Quality of Life; D012016:Reference Values; D018570:Risk Assessment; D016896:Treatment Outcome
chemical_list: D004338:Drug Combinations; D004966:Estrogens, Conjugated (USP); D017258:Medroxyprogesterone Acetate