PMID- 32739288
OWN - NLM
STAT- MEDLINE
DCOM- 20201124
LR  - 20201124
IS  - 1532-1932 (Electronic)
IS  - 1521-6934 (Linking)
VI  - 69
DP  - 2020 Nov
TI  - The pharmacodynamics and safety of progesterone.
PG  - 13-29
LID - S1521-6934(20)30092-4 [pii]
LID - 10.1016/j.bpobgyn.2020.06.002 [doi]
AB  - Natural progesterone (P4) has a unique pharmacodynamic activity and safety 
      profile compared to the synthetic progestins. As a result, a class effect does 
      not exist for both P4 and synthetic progestins, in terms of both their efficacy 
      and safety. Progestogens act at the genomic level by binding to the nuclear 
      receptors and modulating the expression of some target-genes. P4 and the 
      synthetic progestins have a hugely variable affinity for binding not only to the 
      P4 receptors but also to other members of the steroid receptor family including 
      glucocorticoid receptor, androgen receptor and mineralocorticoid receptor. This 
      leads to different and specific pharmacokinetic profiles, clinical 
      pharmacodynamics, safety and efficacy. P4 produced in the luteal phase of the 
      menstrual cycle has several physiological effects regulating menses and, in the 
      pregnant uterus, controlling the development of endometrial receptivity preparing 
      the endometrium for implantation. P4 and its associated metabolites are powerful 
      biological agents through genomic action by the progesterone nuclear receptor 
      with a finely tuned regulatory role throughout pregnancy, from conception until 
      delivery. Extra-nuclear, non-classical mechanisms of action have also been 
      identified, including steroid interactions with some membrane receptors [oxytocin 
      receptors and gamma-aminobutyric acid (GABA(A)), and the induction of a direct 
      relaxing effect on uterine contractility by blockage of calcium influx. The 
      extent of activity of P4 on the central nervous system (CNS) is modulated by the 
      route of administration: oral P4 is affected by the presence of bacteria and 
      associated enzymes secreted in the gut, the intestinal wall and by the liver, 
      whereas vaginal P4 is not. P4 and two important metabolites, namely, 
      allopregnanolone (3a,5a-tetrahydroP4) and 3a,5a-tetrahydrodeoxycorticosterone, 
      exert neuroprotective effects on neonates. They are also natural positive 
      modulators of the neuronal GABA(A) receptor, providing a clear pathway to explain 
      the rapid dose-dependent psychopharmacological actions including anxiolytic, 
      antidepressant, anaesthetic, anticonvulsant and analgesic effects. Fundamental 
      structural differences exist between P4 and the synthetic progestins, resulting 
      in different safety profiles when they are used during the menstrual cycle, in 
      early and late pregnancy and in the alleviation of peri- or postmenopausal 
      symptoms.
CI  - Copyright (c) 2020. Published by Elsevier Ltd.
FAU - Piette, Paul C M
AU  - Piette PCM
AD  - Besins Healthcare Global, Meerweg 119, B 1601, Ruisbroek, Brussels, Belgium. 
      Electronic address: ppiette@besins-healthcare.com.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20200625
PL  - Netherlands
TA  - Best Pract Res Clin Obstet Gynaecol
JT  - Best practice & research. Clinical obstetrics & gynaecology
JID - 101121582
RN  - 0 (Progestins)
RN  - 0 (Receptors, Progesterone)
RN  - 4G7DS2Q64Y (Progesterone)
SB  - IM
MH  - Endometrium
MH  - Female
MH  - Humans
MH  - Infant, Newborn
MH  - Menstrual Cycle
MH  - Pregnancy
MH  - *Progesterone
MH  - *Progestins/adverse effects
MH  - Receptors, Progesterone
MH  - Uterus
OTO - NOTNLM
OT  - Micronised progesterone
OT  - Pharmacodynamics
OT  - Pharmacokinetics
OT  - Progesterone
OT  - Progestins
OT  - Progestogens
COIS- Declaration of competing interest The author is a consultant at Besins Healthcare 
      Global.
EDAT- 2020/08/03 06:00
MHDA- 2020/11/25 06:00
CRDT- 2020/08/03 06:00
PHST- 2020/05/29 00:00 [received]
PHST- 2020/06/04 00:00 [accepted]
PHST- 2020/08/03 06:00 [pubmed]
PHST- 2020/11/25 06:00 [medline]
PHST- 2020/08/03 06:00 [entrez]
AID - S1521-6934(20)30092-4 [pii]
AID - 10.1016/j.bpobgyn.2020.06.002 [doi]
PST - ppublish
SO  - Best Pract Res Clin Obstet Gynaecol. 2020 Nov;69:13-29. doi: 
      10.1016/j.bpobgyn.2020.06.002. Epub 2020 Jun 25.