Understanding Progestins: From Basics to Clinical Applicability
Abstract
:1. Introduction
2. Methods
3. Progestin History
4. Mechanism of Action
- (1)
- Progestational activity: ability to transform the endometrium into the secretory phase and maintain a pregnancy.
- (2)
- Anti-estrogenic activity: ability to downregulate the ER and consequently decrease the thickness of the estrogen-primed endometrium.
- (3)
- Anti-androgenic activity: ability to block T from binding to AR, decreasing the androgen effect and antagonizing 5α-reductase [28].
5. Classification of Progestins
- ○
- Pregnanes: This group can be distinguished by a methyl group at position C10.
- ○
- Norpregnanes: This group includes 19-norprogesterone derivatives and is characterized by the absence of a methyl group at C10 (or lack of C19).
- ○
- Estranes: This group is called ethinylated progestins, and they lack an ethyl group at C13.
- ○
- Gonanes: These are the so-called 13-ethylgonanos, which have an ethyl group at C13 of the basic steroid nucleus.
- ○
- Non-ethylinated: These do not have an ethyl group.
6. Clinical Use of Progestins
6.1. Effect in the Endometrium
6.2. Progestin in Endometriosis
- They reduce estrogen synthesis due to inactivation of the hypothalamic–pituitary–gonadal axis.
- They bind to the ER competitively, providing an anti-estrogenic effect.
- They inhibit the enzyme aromatase (CYP19A1).
- They activate 17-hydroxysteroid dehydrogenase type 2.
- They directly inhibit nuclear factor kappa β, which plays a key role in the processes of inflammation and neoangiogenesis.
- They cause the decidualization of stromal cells, and the secretory transformation of endometrial epithelial cells, which result in endometrial atrophy.
6.3. Progestin in Contraception
- Central action: Inhibiting the secretion of gonadotropic hormones from the pituitary gland (especially LH) and, as a consequence, the inhibition of ovulation (depends on the dose of gestagen in the tablet) [46].
- Peripheral action: Increasing the viscosity of the cervical mucus (by reducing the crypt volume, thickening the cervical mucus, and reducing the sialic acid content in the mucus and sperm activity) has specific effects on the endometrium (progestins suppress the mitotic activity of the endometrium, promoting its premature secretory transformation) and decreases the contractile activity of the fallopian tubes (by reducing the contractility and excitability threshold of the smooth muscle cells of their walls) [46].
6.4. Progestin in Hormone Replacement Therapy
6.5. Progestin in Assisted Reproductive Techniques
7. Summary and Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Progestogen | AE | Est | And | AA | Glu | AM |
---|---|---|---|---|---|---|
Progesterone | ++ | - | - | (+) | + | + |
Chlormadinone acetate | + | - | - | + | + | - |
Cyproterone acetate | + | - | - | + | + | - |
Medroxyprogesterone | + | - | (+) | - | + | - |
Medrogestona | + | - | - | - | ? | - |
Dydrogesterone | + | - | - | - | ? | (+) |
Norethisterone | + | + | + | - | - | - |
Levonorgestrel | + | - | + | - | - | - |
Gestodene | + | - | + | - | (+) | + |
Etonogestrel | + | - | + | - | (+) | - |
Norgestimate | + | - | + | - | ? | ? |
Dienogest | + | - | - | + | - | - |
Tibolone | + | + | ++ | - | - | - |
Drospirenone | + | - | - | + | ? | + |
Trimegestone | + | - | - | (+) | - | (+) |
Promegestone | + | - | - | - | + | - |
Nomegestrol | + | - | - | + | - | - |
Progestational Activity | 19-Norpregnanes * |
---|---|
Antiestrogenic | 19-norpregnanes |
Androgenic | Gonanes |
Antiandrogenic ** | Cyproterone acetate > Dienogest Drospirenone > Trimegestone |
Antimineralocorticoid | Drospirenone |
Glucocorticoid | Medroxyprogesterone acetate |
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García-Sáenz, M.; Ibarra-Salce, R.; Pozos-Varela, F.J.; Mena-Ureta, T.S.; Flores-Villagómez, S.; Santana-Mata, M.; De Los Santos-Aguilar, R.G.; Uribe-Cortés, D.; Ferreira-Hermosillo, A. Understanding Progestins: From Basics to Clinical Applicability. J. Clin. Med. 2023, 12, 3388. https://doi.org/10.3390/jcm12103388
García-Sáenz M, Ibarra-Salce R, Pozos-Varela FJ, Mena-Ureta TS, Flores-Villagómez S, Santana-Mata M, De Los Santos-Aguilar RG, Uribe-Cortés D, Ferreira-Hermosillo A. Understanding Progestins: From Basics to Clinical Applicability. Journal of Clinical Medicine. 2023; 12(10):3388. https://doi.org/10.3390/jcm12103388
Chicago/Turabian StyleGarcía-Sáenz, Manuel, Raúl Ibarra-Salce, Francisco Javier Pozos-Varela, Tania Sofia Mena-Ureta, Susana Flores-Villagómez, Mario Santana-Mata, Ramón G. De Los Santos-Aguilar, Daniel Uribe-Cortés, and Aldo Ferreira-Hermosillo. 2023. "Understanding Progestins: From Basics to Clinical Applicability" Journal of Clinical Medicine 12, no. 10: 3388. https://doi.org/10.3390/jcm12103388
APA StyleGarcía-Sáenz, M., Ibarra-Salce, R., Pozos-Varela, F. J., Mena-Ureta, T. S., Flores-Villagómez, S., Santana-Mata, M., De Los Santos-Aguilar, R. G., Uribe-Cortés, D., & Ferreira-Hermosillo, A. (2023). Understanding Progestins: From Basics to Clinical Applicability. Journal of Clinical Medicine, 12(10), 3388. https://doi.org/10.3390/jcm12103388