Differential effects of unopposed versus opposed hormone therapy, tibolone, and raloxifene on substance p levels

Fertil Steril. 2003 Jul;80(1):96-8. doi: 10.1016/s0015-0282(03)00557-0.


Objective: To evaluate the effects of unopposed therapy (conjugated equine estrogens [CEE]) vs. opposed therapy (CEE and medroxyprogesterone acetate), tibolone, and raloxifene on serum substance p levels.

Design: Clinical study.

Setting: University hospital.

Patient(s): One hundred eight postmenopausal women were assigned to four treatment groups: unopposed hormone therapy (HT) (n = 30), opposed HT (n = 48), tibolone (n = 18), and raloxifene (n = 12).

Intervention(s): Conjugated equine estrogens, CEE and medroxyprogesterone acetate, tibolone, and raloxifene were administered orally; blood samples were collected before therapy and 3 months after.

Main outcome measure(s): Serum substance p levels were measured before and at the end of the third month of the treatment.The serum substance p levels were increased in the unopposed HT group after treatment. On the contrary, substance p levels were decreased in the opposed HT group, in the tibolone group, and in the raloxifene group.

Conclusion(s): Addition of progesterone (P) to estrogen (E) treatment significantly decreases serum substance p levels. Tibolone and raloxifene exert the same effect.

Publication types

  • Clinical Trial
  • Comparative Study
  • Controlled Clinical Trial

MeSH terms

  • Estrogens, Conjugated (USP) / pharmacology*
  • Female
  • Hormone Replacement Therapy / methods*
  • Humans
  • Medroxyprogesterone Acetate / pharmacology*
  • Middle Aged
  • Norpregnenes / pharmacology*
  • Progesterone Congeners / pharmacology
  • Raloxifene Hydrochloride / pharmacology*
  • Selective Estrogen Receptor Modulators / pharmacology
  • Substance P / blood*


  • Estrogens, Conjugated (USP)
  • Norpregnenes
  • Progesterone Congeners
  • Selective Estrogen Receptor Modulators
  • Substance P
  • Raloxifene Hydrochloride
  • Medroxyprogesterone Acetate
  • tibolone