Progestogen-only pills or progestin-only pills (POP) are

contraceptive Birth control, also known as contraception, anticonception, and fertility control, is the use of methods or devices to prevent unwanted pregnancy. Birth control has been used since ancient times, but effective and safe methods of birth contr ...

pills that contain only synthetic progestogens (

progestin A progestogen, also referred to as a progestagen, gestagen, or gestogen, is a type of medication which produces effects similar to those of the natural female sex hormone progesterone in the body. A progestin is a ''synthetic'' progestogen. Pro ...

s) and do not contain

estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal ac ...

. They are colloquially known as mini pills. Although such pills are sometimes called "progesterone-only pills", they do not actually contain progesterone, but one of several chemically related compounds; and there are a number of progestogen-only contraceptive formulations.

Medical uses

The theoretical efficacy is similar to that of the

combined oral contraceptive pill The combined oral contraceptive pill (COCP), often referred to as the birth control pill or colloquially as "the pill", is a type of birth control that is designed to be taken orally by women. The pill contains two important hormones: proges ...

(COCP). 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 COCP's 12 hours). However, in some countries, the POP desogestrel (Cerazette) 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 Sickle cell disease (SCD) is a group of blood disorders typically inherited from a person's parents. The most common type is known as sickle cell anaemia. It results in an abnormality in the oxygen-carrying protein haemoglobin found in red ...

. The progestin-only pill is recommended over regular birth control pills for women who are

breastfeeding Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that bre ...

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 Pelvic inflammatory disease, also known as pelvic inflammatory disorder (PID), is an infection of the upper part of the female reproductive system, namely the uterus, fallopian tubes, and ovaries, and inside of the pelvis. Often, there may be ...

. It is unclear whether POPs provide protection against

ovarian cancer Ovarian cancer is a cancerous tumor of an ovary. It may originate from the ovary itself or more commonly from communicating nearby structures such as fallopian tubes or the inner lining of the abdomen. The ovary is made up of three different ...

to the extent that COCPs do. There are fewer serious complications than with COCPs.

Available forms

Commercially available progestogen-only pills include the following common or widely used formulations: * Desogestrel 75 µg (e.g., Cerazette) * Drospirenone 4 mg (e.g., Slynd)https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211367s000lbl.pdf * Norethisterone 350 µg (e.g., Micronor, Nor-QD, Noriday) And the following rare or mostly discontinued formulations: * Etynodiol diacetate 500 µg (e.g., Femulen) * Levonorgestrel 30 µg (e.g., 28 mini, Microval, Norgeston) *

Lynestrenol Lynestrenol, sold under the brand names Exluton and Ministat among others, is a progestin medication which is used in birth control pills and in the treatment of gynecological disorders. The medication is available both alone and in combination w ...

500 µg (e.g., Exluton, Mini-kare) * Norethisterone 300 μg (e.g., Mini-Pe) * Norgestrel 75 µg (or levonorgestrel 37.5 µg) (e.g., Minicon, Neogest, Ovrette) As well as the following completely discontinued formulations: * Chlormadinone acetate 0.5 mg *

Quingestanol acetate Quingestanol acetate, sold under the brand names Demovis and Pilomin among others, is a progestin medication which was used in birth control pills but is no longer marketed. It is taken by mouth. Quingestanol acetate is a progestin, or a synthe ...

0.3 mg (e.g., Demovis, Pilomin) In the

United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country Continental United States, primarily located in North America. It consists of 50 U.S. state, states, a Washington, D.C., ...

, the only progestogen-only pills that are available are the 350-μg norethisterone and 4-mg drospirenone formulations.

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 approximately regular 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 risk

Epidemiological evidence on POPs and

breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or ...

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. The most recent (1999)

IARC IARC may refer to: * International Aerial Robotics Competition * International Age Rating Coalition * International Agency for Research on Cancer * International Arctic Research Center * Israel Amateur Radio Club The Israel Amateur Radio Club ...

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". 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 have not spread to progestogen-only contraceptive use in premenopausal women.

Depression

There is a growing body of research investigating the links between hormonal contraception, such as the progestogen-only pill, and potential adverse effects on women’s psychological health. The findings from a large Danish study of one million women (followed-up from January 2000 to December 2013) were published in 2016, and reported that the use of hormonal contraception, particularly amongst adolescents, was associated with a statistically significant increased risk of subsequent depression. 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. In 2018, 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. Such studies highlight the need for further research into the influence of hormonal contraception, including the progestogen-only pill on women’s psychological health.

Weight gain

There is some evidence that progestin-only contraceptives may lead to slight weight gain (on average less than 2 kg in the first year) compared to women not using any hormonal contraception.

Mechanism of action

The mechanism of action of progestogen-only contraceptives depends on the progestogen activity and dose. * 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. The same cervical mucus changes occur as with very-low-dose progestogens. * High-dose progestogen-only contraceptives, such as the injectables

Depo-Provera Medroxyprogesterone acetate (MPA), also known as depot medroxyprogesterone acetate (DMPA) in injectable form and sold under the brand name Depo-Provera among others, is a hormonal medication of the progestin type. It is used as a method of bir ...

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

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and

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in 1968. However, it was withdrawn in 1970 due to safety concerns pertaining to long-term animal toxicity studies. Subsequently, levonorgestrel 30 µg (brand name Microval) was marketed in

Germany Germany,, officially the Federal Republic of Germany, is a country in Central Europe. It is the second most populous country in Europe after Russia, and the most populous member state of the European Union. Germany is situated betwee ...

in 1971. It was followed by a number of other POPs shortly thereafter in the early 1970s, including etynodiol diacetate,

lynestrenol Lynestrenol, sold under the brand names Exluton and Ministat among others, is a progestin medication which is used in birth control pills and in the treatment of gynecological disorders. The medication is available both alone and in combination w ...

, norethisterone, norgestrel, and

quingestanol acetate Quingestanol acetate, sold under the brand names Demovis and Pilomin among others, is a progestin medication which was used in birth control pills but is no longer marketed. It is taken by mouth. Quingestanol acetate is a progestin, or a synthe ...

. Desogestrel 75 µg (brand name Cerzette) was marketed in

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in 2002 and was the most recent POP to be introduced. It differs from earlier POPs in that it is able to inhibit ovulation in 97% of cycles.

References

{{Progesterone receptor modulators Hormonal contraception Progestogens