Neuroendocrine effects of different estradiol-progestin regimens in postmenopausal women.
OBJECTIVE
New regimens and routes of administration of hormonal replacement therapy (HRT) in climateric women are becoming available. Since there is no information on the neuroendocrine effects of sequential combined treatment with 17 beta-estradiol and a progestin, the present study evaluated the neuroendocrine, clinical vasomotor and psychological changes before and after different sequential combined HRT regimens (17 beta-estradiol plus nomegestrol acetate, or cyproterone acetate, or vaginal progesterone). Vasomotor and behavioral effects were evaluated by using the Kupperman score, while changes in plasma endorphin (beta-END) levels were used as marker of neuroendocrine effects.


METHODS
Postmenopausal women (n = 30) were randomly divided into three groups (ten women for each group); all women received continuous 17 beta-estradiol (50 mg, transdermal) and each group was sequentially treated with different progestins for 12 days/month: group A, cyproterone acetate (5 mg p.o.); group B, nomegestrol acetate (5 mg p.o.); and group C, progesterone (100 mg, vaginal cream). A group of healthy fertile women (n = 8) served as control. Before and after 6 months of HRT, postmenopausal women underwent an evaluation of subjective Kupperman score and two neuroendocrine tests: (a) naloxone (4 mg i.v.) and (b) clonidine (1.25 mg i.v.). Plasma beta-END levels were measured before and at 15, 30, 45, 60 and 90 min after drug injection. Control women were studied by administering the two neuroendocrine tests only once.


RESULTS
Postmenopausal women before HRT showed a pathological Kupperman and no changes of plasma beta-END levels in response to the clonidine and naloxone tests score. On the contrary the increase was significant in healthy women. In each of the three groups of treated women both naloxone and clonidine tests induced a significant increase in plasma beta-END levels (P < 0.01). After 6 months of HRT, an improvement of vasomotor and psychological symptoms was shown by a decrease of Kupperman score.


CONCLUSIONS
The present study indicates that sequential treatment with transdermal 17 beta-estradiol and progestin, no matter which progestin was used, restores the beta-END release, improves vasomotor and psychological symptoms.
Stomati
M
M
Department of Obstetrics and Gynecology, University of Pisa, Italy.
Bersi
C
C
Rubino
S
S
Palumbo
M
M
Comitini
G
G
Genazzani
A D
AD
Santuz
M
M
Petraglia
F
F
Genazzani
A R
AR
Santre
M
M
D000279:Administration, Cutaneous; D000284:Administration, Oral; D000726:Androgen Antagonists / Q000008:administration & dosage / Q000627:therapeutic use; D003000:Clonidine / Q000494:pharmacology; D015331:Cohort Studies; D003534:Cyproterone / Q000008:administration & dosage / Q000627:therapeutic use; D004958:Estradiol / Q000008:administration & dosage / Q000627:therapeutic use; D015914:Estrogen Replacement Therapy / Q000009:adverse effects / Q000379:methods*; D005260:Female; D006801:Humans; D008535:Megestrol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D008875:Middle Aged; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009490:Neurosecretory Systems / Q000187:drug effects* / Q000502:physiology; D017698:Postmenopause / Q000097:blood / Q000187:drug effects*; D011374:Progesterone / Q000008:administration & dosage / Q000627:therapeutic use; D045167:Progesterone Congeners / Q000008:administration & dosage / Q000627:therapeutic use; D013565:Sympatholytics / Q000494:pharmacology; D014622:Vaginal Creams, Foams, and Jellies; D014666:Vasomotor System / Q000187:drug effects / Q000502:physiology; D001615:beta-Endorphin / Q000097:blood / Q000187:drug effects* / Q000378:metabolism
D000726:Androgen Antagonists; D009292:Narcotic Antagonists; D045167:Progesterone Congeners; D013565:Sympatholytics; D014622:Vaginal Creams, Foams, and Jellies; C047637:nomegestrol; D009270:Naloxone; D011374:Progesterone; D004958:Estradiol; D001615:beta-Endorphin; D003534:Cyproterone; D008535:Megestrol; D003000:Clonidine