Progestogen-only pill

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Progestin-only pill
Background
SynonymsProgestogen-only pill, mini pill
TypeHormonal
First use1968[1]
Failure rates (first year)
Perfect use0.3%[2]
Typical use9%[2]
Usage
ReversibilityYes[3]
User remindersTaken within same 3-hour window each day[3]
Clinic reviewNot required[4]
Advantages and disadvantages
STI protectionNone[5]
WeightNo clear effect[3]
Period disadvantagesIrregular bleeding[3]
Period advantagesLighter and less painful[5][6]
Medical notes
May be used in high blood pressure or migraines.[3] Affected by some anti-seizure medication.[3]

Progestin-only pills (POP), also known as minipills, are birth control pills that contain progestogen (progestin) and not estrogen.[3] With typical use about 9% become pregnant in the first year, while with perfect use it is 0.3%.[4][3] Other uses include painful periods, endometriosis, and sickle cell disease.[5] Fertility returns immediately after stopping use.[3]

Side effects are few, with no increased risk of blood clots or breast cancer.[3] Though, they may result in irregular vaginal bleeding.[3] Effectiveness requires use at the same time each day.[3] They do not protect against sexually transmitted infections (STIs).[5] They may be used during breastfeeding.[3] They primarily work by stopping the release of eggs.[5]

Progestin-only pills came into medical use in 1968 in France.[1] There are currently a number of progestin-only formulations.[3] One, norgestrel, was approved for over the counter sale in 2023, in the United States.[7][3] No testing is required before starting.[4] In the United States they cost between 25 USD and 200 USD per month as of 2023.[3]

Medical uses

The theoretical efficacy is similar to that of the combined birth control pill (CBCP). However, this pill is taken continuously without any breaks between packets, and traditional progestogen-only pills must be taken to a much stricter time every day (within 3 hours vs. a CBCP's 12 hours). However, in some countries, the POP desogestrel has an approved window of 12 hours. The effectiveness is, therefore, dependent upon compliance.

Lacking the estrogen of combined pills, they are not associated with increased risks of deep vein thrombosis or heart disease. With the decreased clotting risk, they are not contraindicated in the setting of sickle-cell disease. The progestin-only pill is recommended over regular birth control pills for women who are breastfeeding because the mini-pill does not affect milk production (estrogen reduces the amount of breast milk). Like combined pills, the minipill decreases the likelihood of pelvic inflammatory disease.[8]

It is unclear whether POPs provide protection against ovarian cancer to the extent that CBCPs do.

There are fewer serious complications than with CBCPs.[9]

Forms

Commercially available progestin-only pills include the following formulations:[10][11][12][13]

And the following rare or mostly discontinued formulations:[10][11][12][13]

As well as the following completely discontinued formulations:

In the United States, the progestin-only pills include the 350-μg norethisterone and 4-mg drospirenone formulations.[16]

Side effects

  • With no break in the dosage, menstrual flow does not initially occur at a predictable time. Most women tend to establish, over a few months, light to heavy spotting at irregular intervals.
  • May cause mastalgia (breast tenderness, pain) and mood swings, as well as panic attacks, anxiety and depression.
  • Some women may experience abdominal cramps and heavy bleeding.
  • May cause weight gain.

Breast cancer

Epidemiological evidence on POPs and breast cancer risk is based on much smaller populations of users and so is less conclusive than that for COCPs.

In the largest (1996) reanalysis of previous studies of hormonal contraceptives and breast cancer risk, less than 1% were POP users. Current or recent POP users had a slightly increased relative risk (RR 1.17) of breast cancer diagnosis that just missed being statistically significant. The relative risk was similar to that found for current or recent COCP users (RR 1.16), and, as with COCPs, the increased relative risk decreased over time after stopping, vanished after 10 years, and was consistent with being due to earlier diagnosis or promoting the growth of a preexisting cancer.[17][18]

The most recent (1999) IARC evaluation of progestogen-only hormonal contraceptives reviewed the 1996 reanalysis as well as 4 case-control studies of POP users included in the reanalysis. They concluded that: "Overall, there was no evidence of an increased risk of breast cancer".[19]

Recent anxieties about the contribution of progestogens to the increased risk of breast cancer associated with HRT in postmenopausal women such as found in the WHI trials[20] have not spread to progestogen-only contraceptive use in premenopausal women.[21]

Depression

Association of use with depression is unclear as of 2021, with some studies finding lower risks and other studies higher risks.[22] A Danish study of one million women reported that the use of hormonal contraception, particularly amongst adolescents, was associated with a increased risk of subsequent depression.[23] The authors found that women on the progestogen-only pill in particular, were 34% more likely to subsequently take anti-depressants or be given a diagnosis of depression, in comparison with those not on hormonal contraception.[23] A similarly large nationwide cohort study in Sweden amongst women aged 12–30 (n=815,662) found an association, particularly amongst young adolescents (aged 12–19), between hormonal contraception and subsequent use of psychotropic drugs.[24]

Weight gain

Tentative evidence does not show an effect on weight of progestin-only pills, though their may be an increase in fat percentage.[3][25]

Mechanism of action

The mechanism of action of progestogen-only contraceptives depends on the progestogen activity and dose.[21]

  • Very-low-dose progestogen-only contraceptives, such as traditional progestogen-only pills (and subdermal implants Norplant and Jadelle and intrauterine systems Progestasert and Mirena), inconsistently inhibit ovulation in ~50% of cycles and rely mainly on their progestogenic effect of thickening the cervical mucus, thereby reducing sperm viability and penetration.
  • Intermediate-dose progestogen-only contraceptives, such as the progestogen-only pill Cerazette (or the subdermal implant Nexplanon), allow some follicular development (part of the steps of ovulation) but much more consistently inhibit ovulation in 97–99% of cycles.[26] The same cervical mucus changes occur as with very-low-dose progestogens.
  • High-dose progestogen-only contraceptives, such as the injectables Depo-Provera and Noristerat, completely inhibit follicular development and ovulation. The same cervical mucus changes occur as with very-low-dose and intermediate-dose progestogens.

In anovulatory cycles using progestogen-only contraceptives, the endometrium is thin and atrophic. If the endometrium were also thin and atrophic during an ovulatory cycle, this could, in theory, interfere with implantation of a blastocyst (embryo).

History

The first POP to be introduced contained 0.5 mg chlormadinone acetate and was marketed in Mexico and France in 1968.[1][27][13] However, it was withdrawn in 1970 due to safety concerns pertaining to long-term animal toxicity studies.[1][27][13] Subsequently, levonorgestrel 30 µg (brand name Microval) was marketed in Germany in 1971.[15][28] It was followed by a number of other POPs shortly thereafter in the early 1970s, including etynodiol diacetate, lynestrenol, norethisterone, norgestrel, and quingestanol acetate.[15][29] Desogestrel 75 µg (brand name Cerzette) was marketed in Europe in 2002 and was the most recent POP to be introduced.[30][29][31] It differs from earlier POPs in that it is able to inhibit ovulation in 97% of cycles.[29][31]

See also

References

  1. 1.0 1.1 1.2 1.3 Annetine Gelijns (1991). Innovation in Clinical Practice: The Dynamics of Medical Technology Development. National Academies. pp. 172–. NAP:13513. Archived from the original on 2023-07-15. Retrieved 2023-07-11. Syntex was the first to introduce a 0.5 milligram chlormadinone acetate minipill in 1968 in France, although this pill was withdrawn from the market in 1970 when long-term animal toxicity tests for the FDA revealed the occurrence of breast nodules in beagles. Nevertheless, other manufacturers began to pursue minipill development using their own progestogens, and since 1970 a variety of compounds have been introduced.
  2. 2.0 2.1 Trussell, James (2011). "Contraceptive efficacy". In Hatcher, Robert A.; Trussell, James; Nelson, Anita L.; Cates, Willard Jr.; Kowal, Deborah; Policar, Michael S. (eds.). Contraceptive technology (20th revised ed.). New York: Ardent Media. pp. 779–863. ISBN 978-1-59708-004-0. ISSN 0091-9721. OCLC 781956734. Table 26–1 = Table 3–2 Percentage of women experiencing an unintended pregnancy during the first year of typical use and the first year of perfect use of contraception, and the percentage continuing use at the end of the first year. United States. Archived 2013-11-12 at the Wayback Machine
  3. 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 3.12 3.13 3.14 3.15 3.16 Cason, Patty; Cwiak, Carrie; Kowal, Deborah; Edelman, Alison (26 September 2023). Contraceptive Technology (22 ed.). Jones & Bartlett Learning. pp. 419–428. ISBN 978-1-284-25503-4. Archived from the original on 10 April 2024. Retrieved 9 April 2024. Archived 10 April 2024 at the Wayback Machine
  4. 4.0 4.1 4.2 "Progestin-Only Pills - US SPR | CDC". www.cdc.gov. 28 March 2023. Archived from the original on 9 April 2024. Retrieved 9 April 2024. Archived 9 April 2024 at the Wayback Machine
  5. 5.0 5.1 5.2 5.3 5.4 "What is the progestogen-only pill?". nhs.uk. 29 February 2024. Archived from the original on 10 April 2024. Retrieved 9 April 2024. Archived 10 April 2024 at the Wayback Machine
  6. "Side effects and risks of the progestogen-only pill". nhs.uk. 29 February 2024. Archived from the original on 10 April 2024. Retrieved 9 April 2024. Archived 10 April 2024 at the Wayback Machine
  7. Perrone, Matthew (13 July 2023). "First over-the-counter birth control pill gets FDA approval in U.S." CBC. Archived from the original on 15 July 2023. Retrieved 13 July 2023. Archived 15 July 2023 at the Wayback Machine
  8. "IUD users may have higher risk of contracting PID, studies find; pill may have protective effect". Family Planning Perspectives. 12 (4): 206–208. 1980. doi:10.2307/2134786. ISSN 0014-7354. JSTOR 2134786. PMID 7439343. Archived from the original on 2021-02-07. Retrieved 2023-07-11. Archived 2021-02-07 at the Wayback Machine
  9. Borgelt-Hansen Laura (2001). "Oral Contraceptives: An Update on Health Benefits and Risks: Progestin-Only Minipill". J Am Pharm Assoc. 41 (6). Archived from the original on 2015-11-01. Retrieved 2023-07-11. Archived 2015-11-01 at the Wayback Machine
  10. 10.0 10.1 Grimes DA, Lopez LM, O'Brien PA, Raymond EG (2013). "Progestin-only pills for contraception". Cochrane Database Syst Rev (11): CD007541. doi:10.1002/14651858.CD007541.pub3. PMID 24226383.
  11. 11.0 11.1 Hussain SF (2004). "Progestogen-only pills and high blood pressure: is there an association? A literature review". Contraception. 69 (2): 89–97. doi:10.1016/j.contraception.2003.09.002. PMID 14759612.
  12. 12.0 12.1 Sylvia K. Rosevear (15 April 2008). Handbook of Gynaecology Management. John Wiley & Sons. pp. 2–. ISBN 978-1-4051-4742-2. Archived from the original on 15 July 2023. Retrieved 11 July 2023.
  13. 13.0 13.1 13.2 13.3 M.R. Henzl (1978). "Natural and Synthetic Female Sex Hormones". In S.S.C. Yen; R.B. Jaffe (eds.). Reproductive Endocrinology: Physiology, Pathophysiology, and Clinical Management. W.B. Saunders Co. pp. 421–468. ISBN 978-0721696256.
  14. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211367s000lbl.pdf Archived 2020-11-08 at the Wayback Machine[bare URL PDF]
  15. 15.0 15.1 15.2 Population Reports: Oral contraceptives. Department of Medical and Public Affairs, George Washington Univ. Medical Center. 1975. p. A-64. Archived from the original on 2023-07-15. Retrieved 2023-07-11. Distribution and Use of the Minipill. [...] Progestogen & Dose in mg: d-Norgestrel 0.03. Manufacturer: Schering AG. Brand Names: Microlut, Nordrogest. Where & When First Marketed: Federal Republic of Germany 1971.
  16. "Drugs@FDA: FDA Approved Drug Products". United States Food and Drug Administration. Archived from the original on 16 November 2016. Retrieved 6 January 2018. Archived 16 November 2016 at the Wayback Machine
  17. Collaborative Group on Hormonal Factors in Breast Cancer (1996). "Breast cancer and hormonal contraceptives: collaborative reanalysis of individual data on 53,297 women with breast cancer and 100,239 women without breast cancer from 54 epidemiological studies". Lancet. 347 (9017): 1713–27. doi:10.1016/S0140-6736(96)90806-5. PMID 8656904. S2CID 36136756.
  18. Collaborative Group on Hormonal Factors in Breast Cancer (1996). "Breast cancer and hormonal contraceptives: further results". Contraception. 54 (3 Suppl): 1S–106S. doi:10.1016/s0010-7824(15)30002-0. PMID 8899264.
  19. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans (1999). "Hormonal contraceptives, progestogens only". Hormonal contraception and post-menopausal hormonal therapy; IARC monographs on the evaluation of carcinogenic risks to humans, Volume 72. Lyon: IARC Press. pp. 339–397. ISBN 92-832-1272-X. Archived from the original on 2006-09-28. Retrieved 2023-07-11.
  20. Chlebowski R, Hendrix S, Langer R, Stefanick M, Gass M, Lane D, Rodabough R, Gilligan M, Cyr M, Thomson C, Khandekar J, Petrovitch H, McTiernan A (2003). "Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women's Health Initiative Randomized Trial". JAMA. 289 (24): 3243–53. doi:10.1001/jama.289.24.3243. PMID 12824205.
  21. 21.0 21.1 Glasier, Anna (March 20, 2015). "Chapter 134. Contraception". In Jameson, J. Larry; De Groot, Leslie J.; de Krester, David; Giudice, Linda C.; Grossman, Ashley; Melmed, Shlomo; Potts, John T., Jr.; Weir, Gordon C. (eds.). Endocrinology: Adult and Pediatric (7th ed.). Philadelphia: Saunders Elsevier. p. 2306. ISBN 978-0-323-18907-1.
  22. McCloskey, Leanne R.; Wisner, Katherine L.; Cattan, Minaz Kolia; Betcher, Hannah K.; Stika, Catherine S.; Kiley, Jessica W. (1 March 2021). "Contraception for Women With Psychiatric Disorders". American Journal of Psychiatry. 178 (3): 247–255. doi:10.1176/appi.ajp.2020.20020154.
  23. 23.0 23.1 Skovlund, Charlotte Wessel; Mørch, Lina Steinrud; Kessing, Lars Vedel; Lidegaard, Øjvind (2016-11-01). "Association of Hormonal Contraception With Depression". JAMA Psychiatry. 73 (11): 1154–1162. doi:10.1001/jamapsychiatry.2016.2387. ISSN 2168-6238. PMID 27680324.
  24. Zettermark, Sofia; Vicente, Raquel Perez; Merlo, Juan (2018-03-22). "Hormonal contraception increases the risk of psychotropic drug use in adolescent girls but not in adults: A pharmacoepidemiological study on 800 000 Swedish women". PLOS ONE. 13 (3): e0194773. Bibcode:2018PLoSO..1394773Z. doi:10.1371/journal.pone.0194773. ISSN 1932-6203. PMC 5864056. PMID 29566064.
  25. Lopez, LM; Ramesh, S; Chen, M; Edelman, A; Otterness, C; Trussell, J; Helmerhorst, FM (28 August 2016). "Progestin-only contraceptives: effects on weight". The Cochrane Database of Systematic Reviews. 2016 (8): CD008815. doi:10.1002/14651858.CD008815.pub4. PMC 5034734. PMID 27567593. We found little evidence of weight gain when using POCs. Mean weight gain at 6 or 12 months was less than 2 kg (4.4 lb) for most studies. The groups using other birth control methods had about the same weight gain.
  26. Pattman, Richard; Sankar, K. Nathan; Elewad, Babiker; Handy, Pauline; Price, David Ashley, eds. (November 19, 2010). "Chapter 33. Contraception including contraception in HIV infection and infection reduction". Oxford Handbook of Genitourinary Medicine, HIV, and Sexual Health (2nd ed.). Oxford: Oxford University Press. p. 360. ISBN 978-0-19-957166-6. Ovulation may be suppressed in 15–40% of cycles by POPs containg levonorgestrel, norethisterone, or etynodiol diacetate, but in 97–99% by those containing desogestrel.
  27. 27.0 27.1 Bennett, John P. (1974). "The Second Generation of Hormonal Contraceptives". Chemical Contraception. pp. 39–62. doi:10.1007/978-1-349-02287-8_4. ISBN 978-1-349-02289-2. Chlormadinone acetate was the first minipill contraceptive to be marketed, in Mexico during July 1968. This compound was removed from clinical use in February 1970 because it produced nodules in the breast tissues of beagle dogs [...]
  28. Greenberg (19 February 2016). Exploring the Dimensions of Human Sexuality. Jones & Bartlett Learning. pp. 481–. ISBN 978-1-284-11474-4. Archived from the original on 15 July 2023. Retrieved 11 July 2023. The progestin-only pill was introduced in 1972.
  29. 29.0 29.1 29.2 Amy Whitaker; Melissa Gilliam (27 June 2014). Contraception for Adolescent and Young Adult Women. Springer. pp. 26, 97. ISBN 978-1-4614-6579-9. Archived from the original on 15 July 2023. Retrieved 11 July 2023.
  30. Kathy French (9 November 2009). Sexual Health. John Wiley & Sons. pp. 92–93. ISBN 978-1-4443-2257-6. Archived from the original on 15 July 2023. Retrieved 11 July 2023.
  31. 31.0 31.1 J. Larry Jameson; Leslie J. De Groot (18 May 2010). Endocrinology - E-Book: Adult and Pediatric. Elsevier Health Sciences. pp. 2424–. ISBN 978-1-4557-1126-0. Archived from the original on 15 July 2023. Retrieved 11 July 2023. In 2002, a POP containing desogestrel 75 ug/day, a dose sufficient to inhibit ovulation in almost every cycle, was introduced in Europe.51

External links