8 Types of Progestin in Combination Birth Control Pills

Hormonal effects differ for progestins

All combination birth control pills contain estrogen (typically ethinyl estradiol) and one of eight kinds of progestin. The term progestin is used for any natural or man-made substance that has properties similar to natural progesterone. Progestins are categorized by generation, which indicates only when they were introduced to the market and not a difference in their chemical structure or how they act.

To best understand how a progestin may be classified, it is helpful to clarify the types of effects a progestin may have on the female body:

  • Progestational effects help prevent ovulation and lessen menstrual bleeding.
  • Androgenic effects are considered unwanted side effects such as acne and body hair growth.
  • Estrogenic effects depend mostly on the amount of ethinyl estradiol in the pills. These effects help counter the androgenic effects.

1
Norethindrone

Assorted contraceptive pills in their packaging
ADAM HART-DAVIS/SCIENCE PHOTO LIBRARY/Getty Images

Norethindrone is a first-generation progestin available in monophasic, biphasic and triphasic formulations. It has low progestational and slight estrogenic activity. It tends to be less androgenic than the second-generation progestins (levonorgestrel and norgestrel), but more androgenic than newer progestins, like desogestrel. In low doses (any pill containing less than 50 mcg of ethinyl estradiol), this progestin improves lipid profiles by raising HDL and lowering LDL cholesterol.

2
Norethindrone Acetate

Norethindrone acetate is a progestin of low progestational activity and slight estrogenic effects. It is a first-generation progestin. It tends to be less androgenic than the second-generation progestins, but more androgenic than newer progestins, like desogestrel. The brand Estrostep was designed to more closely mimic a woman's natural menstrual cycle by providing increasing levels of estrogen with a constant progestin dose. It is the only triphasic brand with this progestin. This brand may be helpful for women who experience minor estrogen-related side effects such as nausea, migraines, or fluid retention with other pill combinations.

3
Ethynodiol Diacetate

Ethynodiol diacetate is a first-generation progestin of medium progestational activity. It has minor estrogenic effects and little androgenic activity. Ethynodiol diacetate is a derivative of norethindrone, so it is easily converted to norethindrone within the body. Birth control pills containing ethynodiol diacetate tend to be associated with increased early or mid-cycle breakthrough bleeding and spotting as compared to other combination pills. However, higher estrogen dosages can counteract the likelihood of breakthrough bleeding, so pill brands that contain higher levels of estrogen can alleviate this side effect.

4
Levonorgestrel

Levonorgestrel is a second-generation progestin and is the most widely prescribed contraceptive progestin worldwide. It has high progestational and androgenic effects. Levonorgestrel negatively affects serum lipoproteins. Several low-dose estrogen brands containing this progestin are available. Levonorgestrel birth control has also been FDA approved for emergency contraception (such as Plan B One-Step and Next Choice). The FDA has stated that all combination pills with this progestin are safe and effective for emergency contraception under the Yuzpe method. The FDA has also approved three extended cycle pill brands that use this progestin—Seasonale, Seasonique, and Lybrel.

5
Norgestrel

Norgestrel (a second-generation progestin) is a mixture of both an inactive and active isomer—dextro-norgestrel (inactive) and levonorgestrel (biologically active). Norgestrel has high progestational and strong antiestrogen effects while also being high in androgenic activity. 

6
Desogestrel

Desogestrel is a third-generation progestin with high progestational selectivity, minimizing androgenic effects and estrogenic activity. It shows a lower negative impact on metabolism, weight gain, acne, and other side effects typical of older progestins. It shows positive effects on lipoproteins as seen by a slight rise of HDL cholesterol. Clinical trials show a possibly higher risk of non-fatal venous thrombosis with desogestrel pills versus those with levonorgestrel. Mircette (a low-dose estrogen/desogestrel pill) provides a shorter placebo interval, which may be helpful for women who have migraines, dysmenorrhea, or other negative issues during that week. A low estrogen/varying desogestrel triphasic pill, Cyclessa, is also available.

7
Norgestimate

Norgestimate, a third-generation progestin, has high progestational activity while showing slight estrogenic effects and tends to be less androgenic. It also has minimal effect on serum lipoproteins as well as on carbohydrate metabolism. The low androgenic effects of norgestimate have resulted in successful treatment of acne. In fact, birth control pills that contain norgestimate are the only ones FDA approved to help reduce acne. Ortho Tri-Cyclen Lo is a brand that provides norgestimate and a mid-level dose of estrogen. So this pill may be helpful in lowering side effects such as nausea and vomiting while not causing an increased incidence of spotting (typically associated with low-estrogen pills).

8
Drospirenone

Drospirenone is the only progestin derived from 17a-spirolactoneis. It helps suppress the secretion of the hormones that regulate the body's water and electrolytes. It also has low androgenic activity. Drospirenone and estrogen seem to lessen symptoms associated with mild PMS (increased appetite, negative mood, and water retention). Drospirenone may cause higher potassium levels, so women with kidney, liver, or adrenal disease should not use it. The brands YAZ and Beyaz have 24 days of active pills and four days of placebo pills. This combination may cause fewer hormone fluctuations than typical pill packs. YAZ has also been FDA-approved to help treat premenstrual dysphoric disorder as well as treat moderate acne in females aged 14 years and up.

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