Difference in signalling between various hormone therapies in endometrium, myometrium and upper part of the vagina.

Background: Combined hormone treatments in post-menopausal women have different clinical responses on uterus and vagina; therefore, we investigated differences in steroid signalling between various hormone therapies in these tissues.

Methods: A total of 30 post-menopausal women scheduled for hysterectomy were distributed into four subgroups: control-group (n = 9), Tibolone-group (n = 8); estradiol (E(2))-group (n = 7); E(2) + medroxyprogesterone acetate (MPA)-group (n = 6). Medication was administered orally every day for 21 days prior to removal of uterus and upper part of the vagina.

Levels of tibolone and estradiol and their nonsulfated and sulfated metabolites in serum, myometrium, and vagina of postmenopausal women following treatment for 21 days with tibolone, estradiol, or estradiol plus medroxyprogestrone acetate.

Tibolone has estrogenic effects on the vagina but not on the uterus. To explain this, levels of tibolone and estradiol and their metabolites were determined in serum, myometrium, and vagina. Thirty-four postmenopausal women with uterine prolapse received either no treatment, tibolone, E(2) or E(2) + medroxyprogesterone acetate (MPA) for 21 days, or a single dose of tibolone.

Estrogen and tibolone metabolite levels in blood and breast tissue of postmenopausal women recently diagnosed with early-stage breast cancer and treated with tibolone or placebo for 14 days.

Unlike estrogens plus progestagens, tibolone, a selective tissue estrogenic activity regulator, does not increase breast tenderness and mammographic density. To elucidate this, serum and breast levels of tibolone and estrogenic metabolites are measured. Postmenopausal women (n = 102) with early-stage, ER(+ve), primary breast cancer received tibolone or placebo for 14 days in an exploratory, double-blind, randomized trial (STEM carcinoma tissue).

7alpha-Methyl-ethinyl estradiol is not a metabolite of tibolone but a chemical stress artifact.

Objective: This study was conducted to establish whether 7alpha-methyl-ethinyl estradiol (7alpha-MEE) in plasma from postmenopausal women treated with tibolone is a metabolite or an artifact.

Design: Clinical samples with known levels of tibolone metabolites, plus plasma samples spiked with tibolone and metabolites, were analyzed for levels of 7alpha-MEE using liquid chromatography-mass spectometry (LC-MS/MS) with and without derivatization.

Results: Approximately 20 to 40 pg/mL 7alpha-MEE was detected using LC-MS/MS with derivatization in plasma samples from postmenopausal women treated with tibolone.

Pharmacokinetic evaluation of three different intramuscular doses of nandrolone decanoate: analysis of serum and urine samples in healthy men.

The pharmacokinetics of nandrolone in serum and urine were investigated in healthy young men after a single im injection of 50 mg (n = 20), 100 mg (n = 17), or 150 mg (n = 17) nandrolone decanoate. Blood samples were collected before treatment and for up to 32 d after dosing. In addition, in the 50- and 150-mg groups, 24-h urine samples were collected before treatment and on d 1, 7, and 33 after treatment; in the 150-mg group, additional samples were collected after 3 and 6 months.

Tibolone is not converted by human aromatase to 7alpha-methyl-17alpha-ethynylestradiol (7alpha-MEE): analyses with sensitive bioassays for estrogens and androgens and with LC-MSMS.

To exclude that aromatization plays a role in the estrogenic activity of tibolone, we studied the effect tibolone and metabolites on the aromatization of androstenedione and the aromatization of tibolone and its metabolites to 7alpha-methyl-17alpha-ethynylestradiol (7alpha-MEE) by human recombinant aromatase. Testosterone (T), 17alpha-methyltestosterone (MT), 19-nortestosterone (Nan), 7alpha-methyl-19-nortestosterone (MENT) and norethisterone (NET) were used as reference compounds. Sensitive in vitro bioassays with steroid receptors were used to monitor the generation of product and the reduction of substrate.

Receptor profiling and endocrine interactions of tibolone.

The receptor profiles and in vivo activity of tibolone, and its primary metabolites, Delta(4)-isomer, and 3alpha- and 3beta-hydroxytibolone, were studied and compared to those of structurally related compounds. The Delta(4)-isomer was the strongest binder and activator of the progesterone receptor (PR); tibolone was 10 times weaker in binding and half as potent in transactivation of PR; 3alpha- and 3beta-hydroxytibolone did not bind or activate PR. In rabbits oral tibolone produced a minor progestagenic effect in the endometrium, whereas co-administration of tibolone and the anti-estrogen ICI 164,384 unmasked tibolone's progestagenic effect.