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A molecular illustration of the six different kinds of progestins.

Illustrations by Marta Pucci

Sex

Progestins 101

What you should know about the synthetic form of progesterone.

by Laurie Ray, Science Writer at Clue Reviewed by Nicole Telfer, Science Content Producer
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Hormones are so much more interesting than what we’re taught in health class.  So we’ve created a guide to aaaall of the hormones. Here's everything you need to know about estrogen, progesterone, androgens, progestins, synthetic estrogen, and sex hormone binding globulin (SHBG)

Top things to know

  • Progestins in hormonal birth control inhibit ovulation and/or reduce the amount and stretchiness of cervical mucus, making it unfriendly to sperm 

  • The chemical structure of progestins is different from natural progesterone, which means the way they interact with the hormone receptors in your body is also different

  • Side effects of progestins can be related to the dose or strength, the specific hormone receptors that it interacts with, or a person’s individual response

  • When progestins are combined with estrogens, side effects may not always be straightforward or easy to predict, since the two components can interact and sometimes counteract each other

What are progestins?

Progestins are synthetic forms of the body’s naturally-occurring hormone progesterone

Progestins were designed to interact with progesterone receptors in the body in order to cause progesterone-like effects (1,2). This means that they do some of what the body’s natural progesterone does. For instance, progestins can cause changes to the endometrium (the lining of the uterus) that prevent it from proliferating (building up) too much, and that can help it support implantation and the continuation of an early pregnancy (1,2,3).

Progestins were originally developed because natural progesterone isn't absorbed well when taken as a pill by mouth and is metabolized (processed) by the body too quickly to have much effect (2,4). Now progesterone is available in a micronized (smaller particle) form that is absorbed easier and lasts longer in the body (4), but only progestins—not micronized progesterone—are used in birth control.

What are progestins used for?

Progestins in hormonal birth control

Progestins are present in all forms of hormonal birth control, either alone in progestin-only methods (like the implant, hormonal IUDs, injection, or mini-pill) or with an estrogen in combined hormonal birth control (like most pills, patch, vaginal ring, and some injections) (4). 

Progestins prevent pregnancy by inhibiting ovulation and reducing the amount and stretchiness of cervical mucus, making it unfriendly to sperm that are trying to enter the uterus (2,4). 

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Some common progestins and the type of birth control they are found in:

Progestin-only birth control and irregular bleeding and spotting

In combined hormonal birth control, it is mainly the progestin that is preventing pregnancy by suppressing ovulation and inhibiting the secretion of stretchy, fertile mucus (2,4). 

The purpose of estrogen in combined hormonal birth control is to make bleeding predictable (4). Without the estrogen, progestin-only methods commonly cause changes in menstrual bleeding (5,6)

Non-cyclical (or unpredictable) bleeding or spotting is common with the hormonal IUD, etonogestrel implant, injection, or mini-pill (7,8). This type of bleeding typically decreases over time for people using the hormonal IUD and injection (7). Amenorrhea (the absence of menstrual bleeding), is possible with all progestin-only methods (7,8). Heavy bleeding is uncommon with the hormonal IUD and implant, but may be a side effect for people using the injection (7).

Progestins in menopausal hormone therapy

Estrogen is sometimes prescribed for people experiencing symptoms related to menopause, such as hot flashes or vaginal dryness (9). Estrogen (whether naturally occuring in the body or taken as a medication) causes the endometrium to grow so that it builds a thick layer (10). Too much estrogen can cause an overgrowth of the endometrium, which is a risk factor for endometrial cancer (9,10). 

Progestins are sometimes used as part of menopausal hormone therapy because they prevent the endometrium from building up too much and becoming cancerous (2,4,9). 

Other uses of progestins

Progestins are prescribed for amenorrhea (the absence of periods) and irregular menstrual bleeding (4). They are also used to treat the chronic pelvic pain and period cramps experienced by people with endometriosis (11). 

How do progestins differ from natural progesterone?

Before we get into potential side effects of progestins, some important background info. 

If you are wondering whether to take a progestin-containing birth control or medication, it’s important to know about the different kinds of progestin and how they might affect your body.

Progestins are created in a lab, usually starting with a hormone as a building block. Most progestins are created from testosterone, some from progesterone, and one is a type of spirolactone (class of synthetic hormones that can impact the body’s salt and water balance) (1,2,4). 

Progestins are sometimes grouped in "generations," which refer to how long they have been on the market. A more useful classification system to understand their effects is to group them by structure based on the hormone from which they were created (4). 

The chemical structure of progestins is different from natural progesterone. These small changes in shape will impact the way they interact with hormone receptors in your body. 

Progestins may attach to more than just progesterone receptors in the body. 

Progestins may also bind to receptors for:

  • androgens

  • estrogens

  • other hormones, like mineralocorticoids, or glucocorticoids (hormones produced by the adrenal glands)

If progestins bind to these receptors, they can cause different side effects—depending on whether the progestin activates or blocks the receptor (2).

That doesn’t necessarily mean there will be any noticeable changes for someone (2). For example, just because a progestin is androgenic (binds to androgen receptors), doesn’t necessarily mean someone taking that progestin will notice androgen-like effects such as increased acne or excess hair growth.

Progestin side effects

If there are progestins in your birth control, hormone therapy, or how you manage medical conditions, you may experience side effects. 

Side effects of progestin can be related to:

  • the dose or strength of a particular progestin (5)

  • the specific hormone receptors with which the progestin is interacting (5) 

  • or a person’s individual response to a progestin 

Understanding what causes side effects can be further complicated by the fact that different effects may be produced when a progestin is combined with different doses of estrogen. 

When progestins are combined with estrogens (as they are in combined hormonal birth control), the side effects may not always be straightforward or easy to predict, since the two components can interact and sometimes counteract each other (5). 

Not everyone’s response to birth control will be the same, but for some people the specific formulation and type of progestin will matter. Sometimes a simple change in dose or type of birth control can improve side effects.

Birth control side effects related to the dose or potency of progestin

Birth control side effects can occur if the dose of progestin isn’t high enough (progestin deficiency) or if the attachment between the progestin and the progesterone receptors isn’t strong enough, due to the slightly different shapes of different progestins (5). 

Side effects related to progestin deficiency

  • bleeding or spotting while taking active (hormone-containing) birth control pills during days 10-21 of the pill pack

  • heavy withdrawal bleeding

  • increased cramping (5)

Someone could also experience side effects if the progestin dose is higher than the progesterone levels their body are naturally accustomed to.

Side effects related to progestin excess

  • elevated blood pressure

  • feeling tired or sleepy

  • hypoglycemia (low blood sugar)

  • decrease in period length (5)

Androgen-related side effects of progestins in birth control

Progestins that bind to androgen receptors can cause androgen-like side effects in some people, such as acne, hirsutism, or changes in cholesterol (2,4,12). 

Androgen-like side effects are particularly present for people using progestin-only birth control methods—like the hormonal IUD, minipill, implant, or injection—which contain no estrogen (12). 

If you suspect that your birth control is causing acne, hirsutism, or other androgenic-changes, it helps to figure out which progestin is in your particular method and see if it is an androgenic progestin.

Androgenic progestins 

  • levonorgestrel (implant, hormonal IUDs, pill, emergency contraception)

  • norethindrone (mini-pill)

  • norethindrone acetate (pill)

  • norgestimate (pill)

  • desogestrel (pill, mini-pill)

  • etonogestrel (implant, vaginal ring)

  • norelgestromin (patch)

  • gestodene (pill)

  • medroxyprogesterone acetate (weakly) (injection/shot) (1,2,5,13)

Anti-androgenic side effects of progestins in birth control

In general, combined hormonal birth control methods—ones with both progestin and estrogen— improves androgen-related effects like acne and hirsutism (14,15).

This is because the estrogen component suppresses the ovaries’ production of androgens, and increases the amount of a protein called sex hormone binding globulin (SHBG). SHBG ties up androgens found in the blood and keeps them from entering the cells in the skin and hair follicles (5,6). 

Some progestins are anti-androgenic themselves, meaning they bind to the androgen receptor and block androgens from attaching to it, but they can’t be activated. These anti-androgenic progestins may be even more beneficial for treating acne and hirsutism when combined with estrogen, because they lower the amount of androgen available in the blood and also block androgens (1,16). 

Anti-androgenic progestins

  • chlormadinone acetate (pill)

  • cyproterone acetate (pill)

  • drospirenone (pill)

  • dienogest (pill) (1,2,5,13)

Bloating and other progestin side effects

Progestins that bind to mineralocorticoid or glucocorticoid receptors can cause side effects related to salt and water balance in the body (1). Mineralocorticoids and glucocorticoids are hormones produced by the adrenal glands, which sit on top of the kidneys. 

Progestins that bind to glucocorticoid receptors and increase glucocorticoid activity, can cause bloating (1). 

Progestins with glucocorticoid activity

  • chlormadinone acetate (pill)

  • cyproterone acetate (pill)

  • medroxyprogesterone acetate (injection/shot)

  • gestodene (weakly) (pill)

  • etonogestrel (weakly) (implant, vaginal ring) (2)

On the other hand, progestins that bind to mineralocorticoid receptors and have anti-mineralocorticoid activity can decrease water retention and bloating (1).

Progestins with anti-mineralocorticoid activity

  • gestodene (pill)

  • drospirenone (pill) (1,2)

Progestins and the risk for blood clots

Deep vein thrombosis (DVT) is a condition where blood clots develop in the veins (often in the legs), and can be life-threatening if they travel to the lungs, heart, or brain. 

Progestin-only methods are generally not thought to increase risk for blood clots (17,18). But when combined with estrogen in combined hormonal birth control, the type of progestin may make a difference in the risk for blood clots (1,18). 

A large study in Denmark showed that people using birth control containing the progestins desogestrel, gestodene, and drospirenone were twice as likely to develop a blood clot in a vein than people using birth control containing levonorgestrel (18). Another study that combined data from six studies did not find a connection between progestin type and the risk for blood clots (19).

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