- Multicenter, phase III trials on the contraceptive efficacy, tolerability and safety of a new drospirenone only pill. [Journal Article]
- AOActa Obstet Gynecol Scand 2019 Jul 18
- CONCLUSIONS: This is the first report of a new drospirenone only oral contraceptive providing clinical efficacy like combined oral contraceptives, with a good safety profile, and favourable cycle control. This article is protected by copyright. All rights reserved.
- Prostaglandin affects in vitro ovulation and 17α, 20β-Dihydroxy- 4-pregnen-3-one production in longchin goby, Chasmichthys dolichognathus oocytes. [Journal Article]
- DRDev Reprod 2019; 23(2):111-117
- This study focused on the association of prostaglandins and a progestin, 17α, 20β-dihydroxy-4-pregnen-3-one (17α20βP) during the ovulation process in longchin goby, Chasmichthys dolichognathus. We pe…
This study focused on the association of prostaglandins and a progestin, 17α, 20β-dihydroxy-4-pregnen-3-one (17α20βP) during the ovulation process in longchin goby, Chasmichthys dolichognathus. We performed several in vitro experiments using 850-920 μm diameter oocytes which were at the migratory nucleus stage. With the 890-920 μm diameter oocytes, no significant difference in ovulation was observed in any of the prostaglandins (PGE1, PGE2, and PGF2α) treated groups although PGE2 and PGF2α at concentrations of 50 ng/mL increased ovulation slightly compared with controls; however, 17α20βP production was stimulated with PGE1 alone at low concentrations (5 ng/mL). In 850 μm diameter oocytes, PGF2α at concentrations of 50 and 500 ng/ml resulted in a significant increase in ovulation. 17α20βP (50 ng/ml) alone had no observable effect on ovulation, but in the combined of PGF2α 50 or 500 ng/ml it caused the greatest effect on ovulation. The sensitivity of oocytes to the induction of ovulation varies between 850 and 890-920 μm, it appeared to vary depending on the migration status of nucleus. These results suggest that PGF2α (or combined of 17α20βP) was more potent in inducing ovulation of the longchin goby.
- Male-biased zebrafish sex differentiation and metabolomics profile changes caused by dydrogesterone. [Journal Article]
- ATAquat Toxicol 2019 Jul 11; 214:105242
- Some progestins, including the widely used dydrogesterone (DDG), have been shown to cause male-biased sex ratio in teleost. However, there is a gap to fully understand the mechanisms of the sex diffe…
Some progestins, including the widely used dydrogesterone (DDG), have been shown to cause male-biased sex ratio in teleost. However, there is a gap to fully understand the mechanisms of the sex differentiation disturbance by progestins, particularly from the metabolic aspect. We thus aimed to examine the sex changes by exposing zebrafish embryos to 4.4 (L), 44 (M) and 440 (H) ng/L DDG for up to 140 days, and investigated metabolomic profile changes during the critical period of sex differentiation at fry stage (35 dpf). DDG increased the percentage of male zebrafish in a dose-dependent manner, with 98% male fish in the high concentration group. In zebrafish fry, DDG increased the levels of some free fatty acids, monoglycerides, acylcarnitines, organic acids, free amino acids, while decreased lysophospholipids, uric acid and bile acids. DDG exposure also decreased the nucleoside monophosphates and UDP-sugars while increased nucleosides and their bases. These metabolite changes, namely increase in n-3 PUFAs (polyunsaturated fatty acids), myo-inositol, taurine, palmitoleic acid, oleic acid, lactic acid, fumaric acid, and uracil, and decrease in uric acid and bile acids, might account for the male-biased sex ratio in zebrafish. It appears that many of these metabolites could inhibit several pathways that regulate zebrafish gonad differentiation, including NF-κB/COX-2 and Wnt/β-catenin pathways, and activate p53 pathway. Thus we proposed a hypothesis that DDG might induce oocytes apoptosis through the above pathways and finally lead to female-to-male sex reversal. The results from this study suggest that DDG at environmentally relevant concentrations could affect zebrafish metabolomic profiles and finally disturb fish sex differentiation.
- Clinical utility of chlormadinone acetate (Lutoral™) in frozen-thawed embryo transfer with hormone replacement. [Journal Article]
- RMReprod Med Biol 2019; 18(3):290-295
- CONCLUSIONS: These results indicate that the pregnancy rate following frozen-thawed embryo transfer using chlormadinone acetate for luteal phase support was comparable with that using vaginal progesterone, with no increased risk of birth defects, including hypospadias, which has been a concern following the use of progestins.
- Pubertal development after unintended intrauterine exposure to oral contraceptives: a nationwide cohort study. [Journal Article]
- FSFertil Steril 2019 Jul 13
- CONCLUSIONS: This study shows some evidence that intrauterine exposure to oral contraceptives might slightly affect pubertal timing.
- Is dienogest the best medical treatment for ovarian endometriomas? Results of a multicentric case control study. [Journal Article]
- GEGynecol Endocrinol 2019 Jul 16; :1-3
- Ovarian endometriomas are common manifestations of endometriosis. Surgical excision has been shown to potentially decrease ovarian reserves. In this prospective study, we included 81 patients with ov…
Ovarian endometriomas are common manifestations of endometriosis. Surgical excision has been shown to potentially decrease ovarian reserves. In this prospective study, we included 81 patients with ovarian endometriosis. 40 were treated with 2 mg of dienogest daily (DNG) and 41 were treated with cyclic oral estro-progestins (ethinyl estradiol 30 mcg [EE] plus dienogest 2 mg) (DNG + EE). Aim of the study was the effect of the treatment on the size of the endometriotic cysts. Further, in the symptomatic patients, follow-up included an evaluation of chronic pain before and during treatment. Both treatments were able to significantly decrease the pain in symptomatic patients with no statistical differences. The mean visual analog scale score at enrollment was 65 ± 14 and 70 ± 18, and there was significant improvement (19 ± 15, p < .001, DNG; 18 ± 12, p < .001, DNG + EE). The size of the endometrioma cysts were significantly reduced in the DNG group. The mean cyst diameter was 52 ± 22 mm at baseline and 32 ± 12 mm after six months of treatment (p < .001), yielding a 75% volume reduction in DNG group. The decrease in the size of endometrioma cysts observed in the women treated with only progestin could be noteworthy, as it may reduce the negative impacts on the affected ovary and avoid surgery.
- Variations in sleep associated with different types of hormonal contraceptives. [Journal Article]
- GEGynecol Endocrinol 2019 Jul 17; :1-5
- Progesterone and some of its metabolites are neuroactive steroids that affect sleep by increasing melatonin secretion and stimulating GABA-A receptors. The effect of progestogens in hormonal contrace…
Progesterone and some of its metabolites are neuroactive steroids that affect sleep by increasing melatonin secretion and stimulating GABA-A receptors. The effect of progestogens in hormonal contraceptives on sleep has not been thoroughly investigated. This observational study assessed possible associations in sleep changes induced by estrogen-progestogens in contraceptives in 108 women between the ages of 20 and 50 years. We assessed mean nightly sleep time with a 31-day sleep diary, and subjective sleep quality with the five subjective subscores of the Pittsburgh Sleep Quality Index (PSQI). Included women were of childbearing age, healthy, sexually active and had been using a hormonal contraceptive method (pill, intrauterine system (IUS), subcutaneous implant, vaginal ring) for at least six months. Results were compared to a matched control group that did not use hormonal contraceptives. The longest mean nightly sleep time, compared to control (450 min), occurred in women who used progestogen-only oral contraception (510 min), followed by IUS delivery of levonorgestrel 13.5 mg (480 min) and oral ethinylestradiol 0.02/0.03 mg plus gestodene 0.075 mg (475 min). Global subjective sleep quality was influenced most by the administration of etonorgestrel 0.120 mg/ethinylestradiol 0.015 mg via the vaginal route. Our results show that low-doses of progestins affect various aspects of sleep, and that this is influenced by the route of administration.
- A pharmacokinetic and pharmacogenetic evaluation of contraceptive implants and antiretroviral therapy among women in Kenya and Uganda. [Journal Article]
- AIDSAIDS 2019 Jul 10
- CONCLUSIONS: Concomitant use of efavirenz significantly reduces levonorgestrel or etonogestrel concentrations by 61% and 49%, respectively, compared to no ART use. We also report allelic variants in hepatic enzymes that influenced the extent of the observed drug-interaction between progestins and efavirenz.
- Depot-medroxyprogesterone acetate reduces genital cell-cell adhesion molecule expression and increases genital herpes simplex virus type 2 infection susceptibility in a dose-dependent fashion. [Journal Article]
- CContraception 2019 Jul 11
- CONCLUSIONS: Mice with pharmacologically relevant serum MPA concentrations display significant changes in genital CCAM expression, genital mucosal barrier function, and HSV-2 susceptibility.
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- Subfertility and reduced progestin synthesis in Pgrmc2 knockout zebrafish. [Journal Article]
- GCGen Comp Endocrinol 2019 Jul 10; :113218
- Progestin receptor membrane component (Pgrmc1 & 2) is a heme-binding protein. Studies on Pgrmc1 have suggested possible roles in heme binding, activation of steroid-synthesizing P450s, along with bin…
Progestin receptor membrane component (Pgrmc1 & 2) is a heme-binding protein. Studies on Pgrmc1 have suggested possible roles in heme binding, activation of steroid-synthesizing P450s, along with binding and transferring of membrane proteins. However, the studies of Pgrmc1's paralog, Pgrmc2 are still lacking. In order to determine the physiologic function(s) of Pgrmc2, we generated a zebrafish mutant line (pgrmc2-/-). We found a reduction in both spawning frequency and the number of embryos produced in female pgrmc2-/-. This subfertility is caused by reduced oocyte maturation (germinal vesicle breakdown, GVBD) in pgrmc2-/- in vivo. Nonetheless, oocytes from pgrmc2-/- had similar sensitivity to 17α,20β-dihydroxy-4-pregnen-3-one (DHP, a maturation induced progestin in zebrafish) compared with wildtype (wt) in vitro. Therefore, we hypothesized that oocyte maturation tardiness found in vivo, could be due to lack of progestin in pgrmc2-/-. Interestingly, we found significant reduced expression of hormones, receptors, and steroid synthesizing enzymes including lhcgr, egfra, ar, and esr2, cyp11a1 and hsd3b1. In addition, DHP levels in pgrmc2-/- ovaries showed a significant decrease compared to those in wt. In summary, we have provided a plausible molecular mechanism for the physiological functions of Pgrmc2 in the regulation of female fertility, likely via regulation of receptors and steroids in the ovary, which in turn regulates oocyte maturation in zebrafish.