Endocrine effects of medroxyprogesterone acetate: relation between plasma levels and suppression of adrenal steroids in patients with breast cancer.
The elimination of adrenal steroids by adrenalectomy or medical treatment has been one of the mainstays in the palliative treatment of patients with disseminated breast cancer. Recently, the effects of progestins on adrenal function has become the subject of renewed interest. To find a relation between plasma levels of medroxyprogesterone acetate (MPA) and adrenal suppression in breast cancer patients, we compared a group of 41 postmenopausal patients with disseminated or inoperable breast cancer, treated with oral MPA, with a control group of 28 postmenopausal breast cancer patients without treatment. To obtain MPA plasma levels in the lower range, 13 patients initially received 300 mg of MPA daily (Group 1), six of whom were subsequently treated with 600 mg (Group 2). Group 3 comprised 37 patients treated with 900 mg of MPA. All of the parameters studied varied widely. Only in Group 3 patients were the MPA levels higher and the levels of cortisol, androstenedione, DHAS, and estrone lower than those in Group 1 patients. All steroid levels in Group 3 were significantly below control values. Considering all data, a negative but weak correlation was found between MPA levels and cortisol (R = -0.55), androstenedione (R = -0.58), and dehydro-epi-androsterone sulfate (R = -0.40), but not for MPA and estrone, indicating better adrenal suppression by higher MPA dosage and plasma levels. However, suppressed cortisol concentrations did not predict sufficient MPA dosage in all patients because low cortisol was not always associated with high MPA levels. A positive relation existed between the levels of androstenedione and estrone, which shows that suppression of these adrenal androgens may result in suppression of plasma estrone. This may be of additional therapeutic benefit in breast cancer patients.
van Veelen
H
H
Willemse
P H
PH
Sleijfer
D T
DT
Sluiter
W J
WJ
Doorenbos
H
H
D000311:Adrenal Glands / Q000187:drug effects* / Q000378:metabolism; D000368:Aged; D000735:Androstenedione / Q000097:blood; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D002986:Clinical Trials as Topic; D003687:Dehydroepiandrosterone / Q000097:blood; D004970:Estrone / Q000097:blood; D005260:Female; D006728:Hormones / Q000097:blood*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008525:Medroxyprogesterone / Q000097:blood / Q000627:therapeutic use*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009426:Netherlands; D011897:Random Allocation
D006728:Hormones; D004970:Estrone; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D008525:Medroxyprogesterone; D006854:Hydrocortisone