Drospirenone increases central and peripheral beta-endorphin in ovariectomized female rats.
OBJECTIVE
Drospirenone is the unique progestin derived from 17-spironolactone used for contraception and hormone therapy. Few data are available concerning the effects of drospirenone on the central nervous system and neuroendocrine milieu. The opioid beta-endorphin and the neurosteroid allopregnanolone are considered markers of neuroendocrine functions, and their synthesis and activity are regulated by gonadal steroids. The aim of the present study was to evaluate the effect of a 2-week oral treatment with drospirenone, estradiol valerate, and combined therapy of drospirenone + estradiol valerate on central and peripheral beta-endorphin and allopregnanolone levels in ovariectomized female rats.


METHODS
Seven groups of Wistar ovariectomized rats received oral drospirenone (0.1, 0.5, and 1.0 mg/kg per day), estradiol valerate (0.05 mg/kg per day), or drospirenone (0.1, 0.5, and 1.0 mg/kg per day) + estradiol valerate (0.05 mg/kg per day). One group of fertile and one group of ovariectomized rats were used as controls. beta-endorphin levels were measured in frontal and parietal lobes, hippocampus, hypothalamus, anterior and neurointermediate pituitary, and plasma, and allopregnanolone content was assessed in frontal and parietal lobes, hippocampus, hypothalamus, anterior pituitary, adrenal glands, and serum.


RESULTS
Ovariectomy induced a significant decrease in beta-endorphin and allopregnanolone content in all brain areas analyzed and in circulating levels, whereas it increased allopregnanolone content in the adrenal gland. Estradiol valerate replacement increased beta-endorphin and allopregnanolone levels in all brain areas analyzed and in plasma/serum. Drospirenone treatment significantly increased beta-endorphin levels in all brain areas analyzed (with the only exception being the parietal lobe), whereas it produced no effect on allopregnanolone levels. The addition of drospirenone to estradiol valerate did not modify the effects of estradiol valerate on beta-endorphin or allopregnanolone levels. Drospirenone showed an additive and synergistic effect with estradiol in the neurointermediate lobe on beta-endorphin synthesis.


CONCLUSIONS
Drospirenone significantly increases central and circulating beta-endorphin levels and does not seem to interfere with allopregnanolone production.
Genazzani
Andrea Riccardo
AR
Department of Reproductive Medicine and Child Development, Division of Gynecology and Obstetrics, University of Pisa, Pisa, Italy. a.genazzani@obgyn.med.unipi.it
Pluchino
Nicola
N
Begliuomini
Silvia
S
Pieri
Matteo
M
Centofanti
Manolo
M
Freschi
Letizia
L
Casarosa
Elena
E
Luisi
Michele
M
D000284:Administration, Oral; D000736:Androstenes / Q000494:pharmacology*; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D010052:Ovariectomy; D011280:Pregnanolone / Q000097:blood / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D001615:beta-Endorphin / Q000097:blood / Q000378:metabolism*
D000736:Androstenes; D004338:Drug Combinations; D000451:Mineralocorticoid Receptor Antagonists; D004958:Estradiol; D001615:beta-Endorphin; D011280:Pregnanolone; C035144:drospirenone