Clinical relevance in present day hormonal contraception
Abstract
The contraceptive pill is an effective and very safe method to control pregnancies. It was developed 60 years ago, and despite that the composition has been the same since it was first developed (estrogen and progestogen), over the years the concentration of ethinyl estradiol has been reduced to improve tolerability. Nevertheless, progestogens are the basic active agent of hormonal contraception. The mechanism of progestogens is a multimodal one and basically three modes of contraceptive action can be distinguished: (a) A strong antigonadotrophic action leading to the inhibition of ovulation. The necessary dosage of ovulation inhibition per day is a fixed dosage that is intrinsic to each progestogen and independent of the dosage of estrogen used or the partial activities of the progestogen or the mode of application. (b) Thickening of the cervical mucus to inhibit sperm penetration and (c) desynchronization of the endometrial changes necessary for implantation. The on the market available progestogens used for contraception are either used in combined hormonal contraceptives (in tablets, patches or vaginal rings) or as progestogen only contraceptives. Progestogen only contraceptives are available as daily oral preparations, monthly injections, implants (2–3 years) and intrauterine systems (IUS). Even the long-acting progestogens are highly effective in typical use and have a very low risk profile. According to their introduction into the market, progestogens in combined hormonal contraceptives, have been described as 1st, 2nd, 3rd and 4th generation progestogens. The different structures of progestogens are derivatives from testosterone, progesterone and spironolactone. These differences in the molecular structure determine pharmacodynamic and pharmacokinetic differential effects which contribute to the tolerability and additional beneficial or therapeutic effects whether used in combined oral contraceptive (COC) or as progestogen only drugs. These differences enhance the individual options for different patient profiles. The new development of polymers for vaginal rings allowed on the one hand, the improvement of the estrogen/progestogen combination in these rings especially regarding the comfort of use for women (e.g. avoiding the use of cold chains or packages with up to 6-month rings) and on the other hand, the development of progestogen only formulations. Another future development will be the introduction of new progestogen only pills that will provide effective contraceptive protection with more favorable bleeding patterns and a maintenance of ovulation inhibition after scheduled 24-h delays in pill intake than the existing progestogen only pill (POP) with desogestrel (DES).
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Hormonal contraceptives contain derivatives of estrogens and progestogens that downregulate regular cyclic hormone activity of the hypothalamic-pituitary-gonadal axis, resulting in physiological responses that differ from those of endogenous ovarian hormones.
“Hormonal contraceptives (HC) contain derivatives of estrogens and progestogens, which downregulate the regular cyclic hormone activity of the hypothalamic-pituitary-gonadal axis, resulting in physiological responses that differ to those of endogenous ovarian hormones [88,93].”
From International society of sports nutrition position stand: nutritional concerns of the female athlete (2023) · cites this paper as [93]
Cites
Medical-eligibility criteria for contraceptive use
Guillebaud, J. (2001) · The Lancet · doi:10.1016/s0140-6736(00)04615-8 · Cited by 1,095 · see citing works
Physiological Action of Progesterone in Target Tissues
Graham, J. D., & Clarke, C. L. (1997) · Endocrine Reviews · doi:10.1210/edrv.18.4.0308 · Cited by 1,007 · see citing works
Classification and pharmacology of progestins
Schindler, A. E., Campagnoli, C., Druckmann, R. A., Huber, J. C., Pasqualini, J. R., Schweppe, K.-W., & Thijssen, J. H. H. (2003) · Maturitas · doi:10.1016/j.maturitas.2003.09.014 · Cited by 741 · see citing works
The Best Intentions: Unintended Pregnancy and the Well-Being of Children and Families
Guttmacher, S. J., Brown, S. S., & Eisenberg, L. (1998) · Journal of Public Health Policy · doi:10.2307/3343096 · Cited by 717 · see citing works
Steroid research at Syntex: “the Pill” and cortisone
Djerassi, C. (1992) · Steroids · doi:10.1016/0039-128x(92)90016-3 · Cited by 461 · see citing works
Reprint of Classification and pharmacology of progestins
Schindler, A. E., Campagnoli, C., Druckmann, R. A., Huber, J. C., Pasqualini, J. R., Schweppe, K.-W., & Thijssen, J. H. H. (2008) · Maturitas · doi:10.1016/j.maturitas.2008.11.013 · Cited by 224 · see citing works
(2005) · Chemistry International · doi:10.1515/ci.2005.27.6.26a · Cited by 209 · see citing works
Non-Contraceptive Benefits of Oral Hormonal Contraceptives
Schindler, A. E. (2012) · Intern J Endocrinol Metab · doi:10.5812/ijem.4158 · Cited by 152 · see citing works
Reducing unintended pregnancy in the United States
Trussell, J., & Wynn, L. L. (2007) · Contraception · doi:10.1016/j.contraception.2007.09.001 · Cited by 142 · see citing works
Rice, C. F. (1999) · Human Reproduction · doi:10.1093/humrep/14.4.982 · Cited by 124 · see citing works
Hormonal contraception and bone metabolism: a systematic review
Nappi, C., Bifulco, G., Tommaselli, G. A., Gargano, V., & Carlo, C. D. (2012) · Contraception · doi:10.1016/j.contraception.2012.04.009 · Cited by 107 · see citing works
The best intentions unintended pregnancy and the well-being of children and families
Brown, S. S., Eisenberg, L., & Institute of Medicine (U.S.) (1995) · Cited by 107 · see citing works
Use of Depot Medroxyprogesterone Acetate and Fracture Risk
Meier, C., Brauchli, Y. B., Jick, S. S., Kraenzlin, M. E., & Meier, C. R. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-0032 · Cited by 90 · see citing works
Non-contraceptive health benefits of intrauterine hormonal systems
Fraser, I. S. (2010) · Contraception · doi:10.1016/j.contraception.2010.05.005 · Cited by 84 · see citing works
Influence of route of administration on progesterone metabolism
Lignieres, B. D., Dennerstein, L., & Bäckström, T. C. (1995) · Maturitas · doi:10.1016/0378-5122(94)00882-8 · Cited by 82 · see citing works
Archer, D. F., Ahrendt, H.-J., & Drouin, D. (2015) · Contraception · doi:10.1016/j.contraception.2015.07.014 · Cited by 78 · see citing works
Update on hormonal contraception and bone density
Isley, M. M., & Kaunitz, A. M. (2011) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-011-9180-6 · Cited by 67 · see citing works
Duijkers, I. J. M., Heger-Mahn, D., Drouin, D., Colli, E., & Skouby, S. O. (2015) · Contraception · doi:10.1016/j.contraception.2015.12.007 · Cited by 67 · see citing works
Regidor, P., & Schindler, A. E. (2017) · Oncotarget · doi:10.18632/oncotarget.19833 · Cited by 59 · see citing works
Self-citationRice, C. F., Killick, S. R., Hickling, D., & Bennink, H. J. T. C. (1996) · Human Reproduction · doi:10.1093/oxfordjournals.humrep.a019245 · Cited by 52 · see citing works
Oral contraceptive use and risk of fractures
Vestergaard, P., Rejnmark, L., & Mosekilde, L. (2006) · Contraception · doi:10.1016/j.contraception.2006.01.006 · Cited by 43 · see citing works
Regidor, P., Colli, E., & Schindler, A. E. (2016) · Gynecological Endocrinology · doi:10.3109/09513590.2016.1161743 · Cited by 42 · see citing works
Self-citationAlgorta, J., Diaz, M., de Benito, R., Lefebvre, M., Sicard, É., Furtado, M., Regidor, P., & Ronchi, C. (2017) · The European Journal of Contraception & Reproductive Health Care · doi:10.1080/13625187.2017.1413179 · Cited by 39 · see citing works
Self-citationKühl, H. (2011) · Journal für Kardiologie (Krause & Pachernegg GmbH) · Cited by 33 · see citing works
Impact of combined and progestogen-only contraceptives on bone mineral density
Sarfati, J., & de Vernejoul, M. C. (2009) · Joint Bone Spine · doi:10.1016/j.jbspin.2008.09.014 · Cited by 27 · see citing works
Long-term effects of progestins on bone quality and fractures
Thijssen, J. H. H. (2007) · Gynecological Endocrinology · doi:10.1080/09513590701584931 · Cited by 8 · see citing works
Jaydess® levonorgestrel intrauterine system
Melvin, L., Scott, J., & Craik, J. (2014) · Journal of Family Planning and Reproductive Health Care · doi:10.1136/jfprhc-2014-100980 · Cited by 7 · see citing works
Hormonimplantate zur Kontrazeption bei der Frau
Rabe, T., Hj, A., Merkle, E., Peters, Κ., Albring, C., Bitzer, J., Kj, B., Egarter, C., König, K., Ludwig, M. Z., et al. (2013) · Journal für Kardiologie (Krause & Pachernegg GmbH) · Cited by 2 · see citing works
Aktuelles: Intrauterine hormonelle Kontrazeption
Römer, T. (2012) · Journal für Kardiologie (Krause & Pachernegg GmbH) · Cited by 2 · see citing works
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“A full overview of the different formulations and mechanism of actions of HCs is out of scope of this position stand, thus the reader is referred to Regidor [94,95] and Benagiano [96] for in-depth detail.”
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Durcik, M., Grobin, A., Roškar, R., Trontelj, J., & Mašič, L. P. (2023) · Chemosphere · doi:10.1016/j.chemosphere.2023.138712 · Cited by 42 · see citing works
Tabatabaie, M., Amiri, S., Jahromi, M. G., Sene, A. A., Zandieh, Z., Mehdizadeh, M., & Amjadi, F. (2022) · Molecular Biology Reports · doi:10.1007/s11033-021-06833-9 · Cited by 20 · see citing works
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Chane, E., Baynes, H. W., Hadgu, R., & Fasil, A. (2023) · PLoS ONE · doi:10.1371/journal.pone.0289746 · Cited by 11 · see citing works
Brouillard, A., Davignon, L., Fortin, J., & Marin, M. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.835857 · Cited by 8 · see citing works
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Xie, H., Qian, T., Liu, L., Sun, R., Che, W., Zhao, M., Hou, X., Pan, H., Su, Y., Li, J., et al. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1362774 · Cited by 1 · see citing works
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Pokrovsky, V. M., Patrakhanov, E. A., Романович, Л. П., Belashova, A. V., Карагодина, А. Ю., Shabalin, A. A., Нестеров, А. В., Markovskaya, V. A., & Pokrovsky, M. V. (2021) · Pharmacy & Pharmacology · doi:10.19163/2307-9266-2020-8-4-255-262 · Cited by 1 · see citing works
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Rizky, A. (2023) · Repository Alungcipta · doi:10.59000/ra.v1i1.2 · Cited by 1 · see citing works
Hormonal contraception: Is it time to abandon estrogen?
de Nadai, M. N., Filho, E. S. F., Magalhães, J., Lubianca, J. N., Sorpreso, I. C. E., Baracat, E. C., & Soares, J. M. (2023) · Human Reproduction Archives · doi:10.4322/hra.000123 · Cited by 1 · see citing works
Combined hormonal contraception: reasons for refusal and use in high-risk women
Кравченко, Е. Н. (2022) · Medical alphabet · doi:10.33667/2078-5631-2022-24-27-30
Contraceptive choice in young people (review of literature and world guidlines)
Владимировна, Д. К., Yavorskaya, S. D., Ремнева, О. В., & Bulanina, O. V. (2022) · Pediatric and Adolescent Reproductive Health · doi:10.33029/1816-2134-2022-18-3-84-98
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Orazov, M. R., Евгеньевич, О. Р., Михалева, Л. М., & Александровна, М. И. (2023) · Medical alphabet · doi:10.33667/2078-5631-2023-3-8-13
Amrani, M., & Gaberle, H.-E. (2023) · Springer eBooks · doi:10.1007/978-3-662-65371-5_11
Magfirah, S. L., & Wijaya, S. (2023) · Tarumanagara Medical Journal · doi:10.24912/tmj.v5i2.24779
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Husaidah, S., Novia, R., Yanita, F., & Heroyanto, H. (2023) · Jurnal Ilmiah Kebidanan dan Kesehatan (JIBI) · doi:10.36590/jibi.v1i1.704
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Pereira, D. C. F., Vantini, D., Shintaku, E., de Carvalho, S. S., da Veiga, G. L., Alves, B. D. C. A., Gascón, T. M., Pereira, E. C., & Fonseca, F. L. A. (2024) · Revista Sociedade Científica · doi:10.61411/rsc202478317
Chane, E., Baynes, H. W., Worede, A., Fetene, G., Mekuanint, A., Eshetu, B., Girma, M., Fentie, A., Feyisa, M. S., Hadgu, R., et al. (2026) · Discover Medicine · doi:10.1007/s44337-026-00591-y
Hu, B., Wu, Y., Xie, Q., Chen, Q., Huang, L., Zhang, J., & Zhang, X. (2026) · Birth · doi:10.1111/birt.70078
- Authors
- Regidor, P.-A.
- Affiliations
- Medical Director, Europe and Germany , Adalperostraße 84, 85737 Ismaning , Germany , Phone: +49 89 4520529 ext. 19, Mobile: +491738938132, Fax: +49 89 4520529 ext. 819
- Corresponding author
- Regidor, Pedro-Antonio
- Venue
- Hormone Molecular Biology and Clinical Investigation
- Publisher
- Walter de Gruyter GmbH
- Published
- 2018-10-26
- Volume
- 37
- Issue
- 1
- ISSN
- 1868-1883 (ISSN-L)
- 1868-1891
- OpenAlex
- W2898922280
- Cited by
- 33
- References
- 29
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 4 · 2023: 9 · 2022: 7 · 2021: 8 · 2020: 2
- FWCI
- 0.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Hormone Molecular Biology and Clinical Investigation (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Health and Contraception
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Pregnancy and Medication Impact
- Keywords
- hormonal contraception, progestogens, combined oral contraceptives, progestin-only contraception, ovulation inhibition, vaginal ring, contraceptive implants, intrauterine system, desogestrel, ethinyl estradiol, tolerability, bleeding patterns, long-acting reversible contraception
- MeSH terms
- Drug Development, Contraception, Contraceptive Agents, Drug Administration Routes, Female, Humans, Intrauterine Devices, Progesterone, Structure-Activity Relationship
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