Comparative Pharmacology of Newer Progestogens

@article{Kuhl2012ComparativePO,
  title={Comparative Pharmacology of Newer Progestogens},
  author={Herbert Kuhl},
  journal={Drugs},
  year={2012},
  volume={51},
  pages={188-215}
}
  • H. Kuhl
  • Published 1 February 1996
  • Medicine
  • Drugs
SummaryThe newer progestogens desogestrel, norgestimate, gestodene, dienogest and nomegestrol share the common property of having weak or no androgenic effects, but there is great variation between agents in their pharmacokinetic properties and hormonal activities. Both desogestrel (acting as 3-keto-desogestrel) and norgestimate (acting mainly through levonorgestrel) are prodrugs. While nomegestrol is derived from 19-norprogesterone, the other compounds are 19-nortestosterone derivatives… 
The use of newer progestins for contraception.
TLDR
Several new progestins have been designed to minimize side-effects related to androgenic, estrogenic or glucocorticoid receptor (GR) interactions, and Dienogest (DNG) and drospirenone (DRSP) exhibit a partial antiandrogenic action, and DRSP has predominant anti-mineraloc Corticoid properties.
Molecular action of norgestimate: new developments
TLDR
It is demonstrated that NG and dNG have full progestogen and weak estrogenic (through ERα) properties, which could explain in part the efficacy of NG in association with EE for the treatment of moderate acne in women.
Progestogens with Antiandrogenic Properties
TLDR
COCs containing antiandrogenic progestogens are likely to be particularly valuable in women with pre-existing androgen-related disorders who require contraception, and increase the choice of products available for women with normal skin and hair who are concerned about the possibility of developing seborrhoea or acne with other COCs.
Nomegestrol Acetate
This review summarizes the pharmacology, safety and clinical efficacy of nomegestrol acetate, based on the available published literature, and assesses the pharmacological characteristics that
Ethynilestradiol 20mcg plus Levonorgestrel 100mcg: Clinical Pharmacology
TLDR
Overall, EE20/LNG100 combination is safe and well tolerated, and in several studies the incidence of adverse events in the treated group was comparable to that of the placebo group.
The paradigm of norgestimate: a third-generation testosterone-derivative progestin with a peripheral anti-androgenic activity and the lowest risk of venous thromboembolism
TLDR
A narrative review of the available data on the pharmacotherapy of NGM in combined hormonal contraceptives (CHCs) in terms of contraceptive efficacy, venous thromboembolism risk, safety, tolerability and bleeding patterns is reviewed.
The challenge presented by progestins in ecotoxicological research: a critical review.
TLDR
The ability to impair female reproduction at very low concentrations makes the progestins arguably the most important pharmaceutical group of concern after ethinylestradiol.
Ethynilestradiol 20 mcg plus Levonorgestrel 100 mcg: Clinical Pharmacology
TLDR
Overall, EE20/LNG100 combination is safe and well tolerated, and in several studies the incidence of adverse events in the treated group was comparable to that of the placebo group.
Molecular mechanisms of steroid receptor-mediated actions by synthetic progestins used in HRT and contraception
TLDR
The molecular mechanisms of intracellular actions of old (MPA, norethisterone, levonorgestrel, gestodene) vs. new (drospirenone, dienogest, trimegestone) generation progestins, via steroid receptors are reviewed.
Evaluation of different antiandrogenic progestins on clinical and biochemical variables in polycystic ovary syndrome
TLDR
DNG exerted an important stimulatory effect on sex hormone-binding globulin (SHBG) and biochemical markers of hyperandrogenism as well as dehydroepiandrosterone sulphate and total testosterone in women with polycystic ovary syndrome.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 135 REFERENCES
Serum distribution of two contraceptive progestins: 3-ketodesogestrel and gestodene.
TLDR
It is concluded that ethinylestradiol-induced increases in serum SHBG levels during treatment with Marvelon or Femovan influenced the distribution and total amount of 3-ketodesogestrel and gestodene in serum, respectively, and that this, combined with the higher affinity of SHBG for Gestodene, results in a greater amount of bioavailable gestodenes compared to 3- ketodesogESTrel, despite the smaller dose of gestodne administered.
The pharmacological profile of norgestimate, a new orally active progestin.
TLDR
Norgestimate has marked antiestrogenic activity and is a potent inhibitor of estrogen-induced vaginal cornification and is being studied clinically in combination with ethinyl estradiol as a new low-dose oral contraceptive.
Receptor binding of norgestimate--a new orally active synthetic progestational compound.
TLDR
The competition experiments suggest that norgestimate is a prodrug and that the metabolites, levonorgestrel and levonborgestrel-17-acetate, which actively bind to the progesterone receptor, must first be formed from the parent drug via metabolic processes in vivo.
Gestodene: a novel synthetic progestin--characterization of binding to receptor and serum proteins.
TLDR
Competitive studies indicated that gestodene like other synthetic progestagens also displays some affinity for androgen and glucocorticoid receptors but no measurable affinity for the estrogen receptor, and remarkable is the high binding affinity of gestodenes to the binding sites of the mineraloc Corticoid receptor of rat kidney with a RBA value of 350% compared to aldosterone.
Comparative progestational activity of norgestimate, levonorgestrel-oxime and levonorgestrel in the rat and binding of these compounds to the progesterone receptor.
TLDR
The combined experimental evidence of the present study does not support the view of NORG being a progestogen on its own as has been suggested by others.
The Selectivity of a New Progestin
  • A. Phillips
  • Medicine
    Acta obstetricia et gynecologica Scandinavica. Supplement
  • 1990
TLDR
Norgestimate is a new progestin developed for use with ethinyl estradiol as a combination oral contraceptive and in the oral form stimulates a progestational endometrial effect in rabbits.
The cellular mechanism of the antiandrogenic action of nomegestrol acetate, a new 19-nor progestagen, on the rat prostate.
TLDR
Since the RBA of nomegestrol acetate declined with time, these results indicate that this substance may act like an antiandrogen rather than an androgen, while the contrary prevails concerning MPA.
Progestational and androgenic receptor binding affinities and in vivo activities of norgestimate and other progestins.
TLDR
Evidence of the selectivity of norgestimate based on minimal androgenicity is provided, indicating an improvement over other progestins used in oral contraceptives.
Desogestrel, a new progestational compound, and the liver.
TLDR
This study shows that with oral contraceptive combinations containing desogestrel and EE (30 or 50 micrograms) liver function is not affected and values normalized in the majority of women during the course of treatment.
Metabolism of the contraceptive steroid desogestrel by human liver in vitro.
TLDR
Interestingly, trilostane was without inhibitory effect on either enzyme, which contrasts with other data involving 3 beta-HSDH in steroidogenic tissue, which may reflect tissue differences in the enzyme and/or differences in endogenous vs exogenous steroids.
...
1
2
3
4
5
...