Types (8) of Progestin in Combination Birth Control Pills

Hormonal effects differ for progestins

There are eight different types of progestin that may be found in combination birth control pills along with estrogen (typically ethinyl estradiol). 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 primarily when they were introduced to the market.

Progestin Effects

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.

Progestin "Generations"

In looking at the specific progestins, it's also helpful to define them by groups. Progestins are classified as first to fourth generation progestins based on when they were first available, but different generations also have some different characteristics. Keep in mind that newer isn't necessarily better.

  • First generation: Norethindrone, norethindrone acetate, and ethynodiol
  • Second generation: Desogestrel and norgestrel
  • Third generation: Norgestrel and norgestimate
  • Fourth generation: Drospirenone

When looking at progestins, it's noteworthy that some combination pills that sound very similar have different progestins. For example, Ortho-novum 1/35 and 7/7/7/ contain norethindrone whereas Ortho-novum 1/50 contains norgestrel.

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.

Advantages: Improves lipid profile; First progestin in use so many years of data on safety; May be helpful in women who experience depression on other oral contraceptive combinations

Disadvantages: In between as to effects on acne

Examples: Nortrel; Brevicon; Modicon; Ortho-novum 1/35; Ortho-novum 7/7/7/; Ovcon

2

Norethindrone Acetate

Norethindrone acetate is another first-generation progestin with low progestational activity and slight estrogenic effects. 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.

Advantages: May help women who experience migraines or nausea on birth control pills

Disadvantages: In between effects on acne

Examples: Loestrin, Junel, Estrostep

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 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.

Advantages: May be helpful for women with endometriosis

Disadvantages: Breakthrough bleeding (spotting)

Examples: Demulen, Kelnor, Zovia

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.

According to a 2018 systematic review, levonorgestrel was associated with the lowest risk of blood clots (venous thromboembolism) of all combined oral contraceptives

Certainly, the lowest possible dose of ethinyl estradiol is recommended as well.

Advantages: Lowest risk of blood clots of all combined oral contraceptives

Disadvantages: Negative effect on lipids (affects serum lipoproteins); increased incidence of androgenic side effects such as acne

Examples: Alesse; Aviane, Portio; Triphasil, Tri-Levelin, Nordette, Extended cycle (continuous birth control) pills including Seasonique, Seasonale, 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. 

Advantages: May be helpful in endometriosis prevention

Disadvantages: Acne; weight gain

Examples: Ovral and Lo/Ovral; Ogestrel and Lo-ogestrel; Cryselle; Ortho-novum 1/50

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 (blood clots) 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.

Along with drospirenone, desogestrel appears to have a higher risk of blood clots than other options, especially levonorgestrel, with the highest risk of all combination birth control pills being desogestrel combined with 30 to 40 micrograms of ethinyl estradiol (see 2017 study below under desogestrel).

Advantages: May help with menstrual cramps; Reduced risk of menstrual migraines; positive effects on lipids; Less weight gain

Disadvantages: Higher risk of blood clots

Examples: Mircette; Ortho-Cept; Apri; Solia; Desogen; Cesia; Reclipsen; Velivet; Casiant

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).

Advantages: The only pill FDA approved to help acne; Little effect on lipids

Disadvantages: May have a higher rate of headaches; Reduced libido

Examples: Ortho Tri-Cyclen Lo; Mylan (generic Ortho Tri-Cyclen; Sprintec, TriNessa, Previfem, Estarylla

8

Drospirenone

Drospirenone is the only progestin derived from 17a-spironolactone. 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 a premenstrual dysphoric disorder.

Drospirenone has been linked to an increased risk of blood clots in several studies. A 2017 review looked at 17 studies that found the risk of blood clots ranged from no increase to a 3.3 times increased risk of blood clots in comparison to levonorgestrel (the birth control pill thought to have the lowest risk). The conclusion was that based on the best studies, the risk is only slightly increased.

Looked in another way, however, some of the same researchers looked at the risk of blood clots in first-time users and restarters of oral contraceptives in over 55,000 women in another 2017 study. They found that the risk of blood clots was 3.19 times higher with drospirenone that with levonorgestrel for first-time users and 1.96 times higher in restarters.

Given this risk, women who have other risk factors for blood clots may wish to consider a birth control pill other than those with drospirenone or desogestrel, or another form of birth control altogether.

Advantages: May help reduce PMS symptoms (PMDD) and acne

Disadvantages: Increased risk of blood clots; Increased serum potassium levels

Examples: YAZ and Beyaz; Yasmin; Zarah; Loryna; Syeda; Gianvi; Ocella; Vestura; Nikki

9

Choosing an Oral Contraceptive

In addition to the type of progestin and dose of estrogen, there are many factors that go into choosing the right birth control pill for you. Fortunately, researchers have done some of the footwork in determining which birth control pills may minimize the most annoying side effects including:

  • Acne
  • Weight gain
  • Breast tenderness
  • Migraines
  • Breakthrough bleeding
  • Menstrual cramps
  • Moodiness and irritability
  • Depression

A Word From Verywell

Understanding the different progestins in various birth control pills can seem overwhelming. Having a thoughtful conversation with your doctor about your goals in contraception, as well as the side effect you most wish to avoid (and those you may be willing to tolerate) is a great start.

Yet it's helpful to be your own advocate as well. Nobody is as motivated as you are to care for your health and well-being. In looking at the types of progestin in different oral contraceptives you are making an excellent start in managing your health care.

Was this page helpful?

Article Sources