Disease relevance of dydrogesterone

• A double-blind, cross-over, placebo-controlled study of dydrogesterone (10 mg b.d.) in the treatment of premenstrual syndrome is described [1].
• Dydrogesterone in threatened abortion: pregnancy outcome [2].
• The role of dydrogesterone in recurrent (habitual) abortion [3].
• The results are reported of the administration of dydrogesterone, 5 mg twice daily, to 49 patients with endometriosis [4].
• Dydrogesterone in the reduction of recurrent spontaneous abortion [5].

Psychiatry related information on dydrogesterone

• An increased tail flick latency following dydrogesterone injection supported the concept that decreased expression of the NK-1R on lymphocytes is associated with an increased pain threshold [6].
• A significant effect of dydrogesterone was found on decreased libido, and statistical significance was nearly achieved for the symptoms irritability and headache [7].

High impact information on dydrogesterone

• Depletion of CD8+ cells abolishes the pregnancy protective effect of progesterone substitution with dydrogesterone in mice by altering the Th1/Th2 cytokine profile [8].
• DBA/2J-mated CBA/J female mice were randomized in three groups: 1) control females, 2) mice exposed to stress on gestation day 5.5, and 3) mice exposed to stress and substituted with dydrogesterone, a progestogen with a binding profile highly selective for the progesterone receptor on gestation day 5 [8].
• In conclusion, unopposed oral estradiol and estradiol combined with dydrogesterone or trimegestone reduced plasma levels of the NOS inhibitor ADMA [9].
• Estrogen replacement therapy continuously combined with four different dosages of dydrogesterone: effect on calcium and lipid metabolism [10].
• In 2 LPD women treated with dydrogesterone, normal endometrial maturation and a decline in endometrial cytosolic PgR concentrations in the late luteal phase were found [11].

Chemical compound and disease context of dydrogesterone

• CONCLUSIONS: Transdermal estrogen substitution alone and combined with cyclical dydrogesterone may ameliorate hyperinsulinemia in a selected population of postmenopausal women [12].
• The influence of diethylether anesthesia, strychnine (0.5 mg/kg) or picrotoxin (0.25 mg/kg) on the latency for the appearance of the lordosis response after IV injection of isopregnenone was studied in estradiol benzoate treated ovariectomized females [13].
• Uteroplacental circulation in early pregnancy complicated by threatened abortion supplemented with vaginal micronized progesterone or oral dydrogesterone [14].

Biological context of dydrogesterone

• OBJECTIVE: To determine whether therapy with dydrogesterone in threatened abortion during the first trimester of pregnancy will improve pregnancy outcome [2].
• The effects of the two dydrogesterone doses on endometrial histology, vaginal bleeding, and the symptomatic and psychological status were compared [15].
• Dydrogesterone given after ovulation did not produce any alteration in endocrine profiles but menses was postponed in both subjects [16].
• Dydrogesterone increases serum lactalbumin concentration in the puerperium [17].
• Estrogen alone and combined with dydrogesterone evoked a significant increase in C-peptide AUC in hyperinsulinemic (79.2%) and normoinsulinemic (113%) patients [12].

Anatomical context of dydrogesterone

• Dydrogesterone induced a decrease in the percentage of NK-1R(+) lymphocytes in vitro and in vivo [6].
• Taken together, these results clearly reveal a pathway by which dydrogesterone or progesterone respectively modulates the cross talk of the nervous, endocrine and immune systems in inflammation and pain [6].
• During dydrogesterone treatment, there is an increase in osteoclast number, without an apparent increase in osteoclast function [18].
• Effects of dydrogesterone on the oestrogenized postmenopausal endometrium [19].
• Middle cerebral artery velocity was significantly increased following dydrogesterone treatment compared with placebo [% (SE) change from baseline D +6.8 (3.4) N +3.9 (4.2) P -4.6% (3.4) P=0.03 for D versus P] [20].

Associations of dydrogesterone with other chemical compounds

• Hormone replacement therapy with dydrogesterone and 17 beta-oestradiol: effects on serum lipoproteins and glucose tolerance during 24 month follow up [21].
• With sequential 17 beta-estradiol/dydrogesterone the expected progestogen-induced secretory pattern was observed, whereas endometrial histology under tibolone closely mimicked the natural atrophic postmenopausal state [22].
• The minimum doses of progestin inducing a comparable response to premenopausal secretory phase endometria were found to be 1-2.5 mg norethindrone, 150 micrograms norgestrel and 20 mg dydrogesterone [23].
• No changes were observed in the tdE2 + DYDR treated women; in this group the shift to NETA addition caused a significant decrease of SHBG values (P < 0.001 vs. before treatment and vs. tdE2 + DYDR phase) and a slight increase of IGF-I values [24].
• Clinical study comparing the effects of sequential hormone replacement therapy with oestradiol/dydrogesterone and conjugated equine oestrogen/norgestrel on lipids and symptoms [25].

Gene context of dydrogesterone

• Additionally, an increase in Th2-type and a decrease in Th1-type cytokines could be detected in vitro after incubation with dydrogesterone [6].
• Replacement with dydrogesterone, a synthetic analog of P4 at a dose of 4 mg/day s.c. restored the magnitude of nocturnal PRL surges [26].
• Human osteoblast-like (HOB) cells were incubated with 17 beta-estradiol (E2), progesterone (P), dydrogesterone (DD), 20 alpha-dihydroxydydrogesterone (DHD), with and without the growth factors, insulin-like growth factors-I/-II (IGF-I/-II) or transforming growth factor-beta type 1 (TGF-beta 1) for 24 h under serum-free conditions [27].
• After dydrogesterone supplementation, mean TNF-alpha/IL-10 ratio changed from 1.08 to 1.75 while IL-12/IL-10 ratio remained almost the same (0.56-0.61) in the threatened aborters group and did not differ from those in healthy women [28].
• Further, dydrogesterone increased levels of plasma PIBF in stressed mice, but did not affect progesterone levels [29].

Analytical, diagnostic and therapeutic context of dydrogesterone

• Analysis of the contribution of dydrogesterone to bone turnover changes in postmenopausal women commencing hormone replacement therapy [30].
• Postmenopausal volunteers (n = 24) received according to a balanced cross-over design, two 28-d treatments separated by a 2-month wash-out period: 300 microg E2, either alone or combined with oral dydrogesterone (20 mg/d) during the last 14 d of one of the treatments [31].
• METHODS: In a prospective, double-blind study, 194 postmenopausal women were allocated randomly to receive one of four doses of dydrogesterone (2.5 mg, 5 mg, 10 mg, 15 mg) continuously combined with 2 mg of micronized 17beta-estradiol [32].
• Abortions were significantly (p < or = 0.05) less common in the dydrogesterone group (13.4%) than in the control group (29%); there were no statistically significant differences between the hCG group and the control group [5].
• Fifty-four patients received dydrogesterone three times daily (TID) beginning on the day of embryo transfer (ET) [33].

References