Why Not All Progestins Are Created Equal — And Why I Am Cautious About the Pill and the Hormonal IUD
By: Jill Chmielewski, May 1, 2026
If you have been told that "the pill is safe," or that the hormonal IUD is just a tiny, local dose, you are not alone. Most women have heard some version of this.
For some women, the pill or the IUD really may be the right choice. But there is a longer conversation that does not always make it into your clinical visit.
This article is about a quiet but important truth in women's health. The synthetic hormones in most birth control pills, and in the hormonal IUD, are not the same as the hormones your body makes. They were built in a lab. Many of them were built from testosterone. And they behave in your breast tissue, your liver, and your brain in ways that are different from your own progesterone.
We will walk through what these hormones really do. We will look at what the studies show. And we will explain why we lean toward body-identical hormones when the goal is long-term tissue health.
Progestin is not progesterone
This is the sentence that gets glossed over most often.
Progesterone is the hormone your ovaries make in robust amounts after you ovulate. (Some progesterone is made in smaller amounts in other tissues. Progesterone is calming. It lowers inflammation. It supports the breast and the brain.
Progestins (also called progestogens) are synthetic, chemically altered progesterone “impostors”. They are designed to fit into the progesterone receptor. But they were built from different starting molecules. And the molecule you start with shapes what the final drug does in the body [1].
There are two main families of progestins.
Progesterone-like progestins are built from progesterone itself. Examples include dydrogesterone, drospirenone, and nomegestrol acetate. These tend to act more like the hormone your body makes.
Testosterone-like progestins are built from a slightly changed form of testosterone called 19-nortestosterone. Examples include norethindrone (also called norethisterone), levonorgestrel, gestodene, desogestrel, and norgestimate. Levonorgestrel is the hormone in the Mirena IUD, in Plan B, and in many older combined birth control pills. Norethindrone is the progestin in many low-dose pills, the mini-pill, and some forms of menopausal hormone treatment [1, 2].
The testosterone-family progestins are the ones we are most cautious about. Here is why.
Androgen receptors in the breast: a quiet protective system
Your breast tissue listens to all hormone signals (and other signals), beyond just estrogen. It also listens to androgens, hormones like testosterone, through tiny receptors called androgen receptors. You can think of these receivers as small satellite stations sitting on and inside your breast cells.
When testosterone reaches these satellite stations in normal breast tissue, the message is “slow down, calm, settle.” In plain terms, androgen signals in the breast tell cells not to overgrow [6, 7]. This is a real and protective system. Some researchers now describe the androgen receptor as a tumor suppressor in breast tissue [6].
This is one reason many women feel better in their breasts when their own testosterone is in a healthy range. The hormone is not just about libido. It is part of how the breast keeps itself healthy.
What testosterone-like progestins really do in the breast
Here is where the standard story falls short.
You might guess that a "testosterone-like" progestin would land on the androgen receptor, support that “calming” signal, and protect the breast. I hoped so too. But the data tells a different story.
Testosterone-like progestins, such as levonorgestrel and norethindrone, do bind the androgen receptor. But they do not act like a gentle, body-identical androgen. They drive the receptor in a more drug-like, activating way [1].
On top of that, they carry three off-target effects in breast tissue that body-identical progesterone does not [1, 8, 9, 10].
They act partly like estrogen. Levonorgestrel, norethindrone, and gestodene can also bind to the estrogen receptor and switch it on. They were prescribed as progestins. They behave, in part, as estrogens. Body-identical progesterone does not do this [1].
Norethindrone can be converted to ethinyl estradiol, a potent synthetic estrogen, in the body. Human tissue has the enzyme that does this [10]. So part of every dose of norethindrone is converted into one of the most potent estrogens we know.
They switch on a protein called PGRMC1 inside breast cells. When PGRMC1 is active, it frees the estrogen receptor to promote cell growth. It also turns on a signal called RANKL, which tells breast cells to multiply [8, 9]. Body-identical progesterone does not trigger this in the same way.
So what looks on paper like "a small dose of progestin" is, at the tissue level, a molecule that can pull three levers of breast tissue growth at once.
For comparison, body-identical progesterone (the kind in micronized progesterone capsules, vaginal progesterone, and topical progesterone) is mildly anti-androgenic, reduces inflammation, and does not activate PGRMC1 in this way [1, 8].
And it is not just the progestin — the estrogen in the pill is far stronger than your own
I want to sit with this one for a minute, because it does not get talked about enough.
The estrogen in most combined birth control pills is called ethinyl estradiol. It is not the same as the estradiol your ovaries make. It is a chemically altered version, designed to survive the trip through your liver so that it can be taken as a pill. That tweak does not just make it last longer. It also makes it much more powerful.
In the body, ethinyl estradiol is roughly 100 to 250 times more potent than the estradiol your own body produces, depending on which tissue you are measuring and which effect you are looking at [12, 13]. That is not a typo. One hundred to two hundred and fifty times.
That is a big deal. Settle on that for a minute.
This is one reason the pill has such a strong effect on the liver — raising clotting factors, raising blood pressure in some women, lowering free testosterone, and changing how the body handles thyroid hormone, cortisol, and vitamin D. It is also one reason the pill can have such a noticeable effect on mood, sex drive, and breast tissue. It is not "a little extra estrogen." It is a synthetic estrogen broadcasting at 100 to 250 times the volume of your own.
So when you stack a testosterone-derived progestin on top of an estrogen that is 100 to 250 times stronger than your own, and that whole combination travels through your bloodstream to every cell in your body — you are not getting a tiny, local, gentle hormonal nudge. You are getting a loud, system-wide signal that does not match the one your body has been making your whole life.
What the breast cancer studies show
This is not just lab theory. The same pattern shows up in large studies of real women.
The French E3N cohort followed more than 80,000 women. Those using estrogen plus bioidentical progesterone had no increase in breast cancer risk compared with non-users (relative risk 1.00). Those using estrogen plus a synthetic, testosterone-derived progestin had a relative risk of 1.69 [3].
A French case-control study found the same pattern. Women using estrogen plus bioidentical progesterone had no increase in breast cancer risk. Women using estrogen plus a testosterone-derived progestin had more than a three-fold higher risk [4].
The UK QResearch and CPRD analysis matched nearly 100,000 women with breast cancer to over 450,000 controls. Norethindrone-based hormone treatment carried the highest breast cancer odds (1.88). Levonorgestrel and medroxyprogesterone landed in the middle. Dydrogesterone had the lowest odds of the combined regimens [2].
The Women's Health Initiative followed women for more than 20 years. Conjugated estrogens alone, in women without a uterus, actually lowered breast cancer rates and breast cancer deaths. The same estrogen, combined with a synthetic progestin (medroxyprogesterone), raised breast cancer rates [5]. The progestin, not the estrogen, was the driver.
A 2026 expert review in The Lancet Diabetes & Endocrinology came to the same conclusion. The progestin you choose matters. Bioidentical progesterone has the most favorable breast profile. And many lifestyle factors carry larger effects on breast cancer risk than the choice between hormone treatment regimens [11].
Where the pill and the IUD fit in
Most combined birth control pills use a testosterone-derived progestin. Usually it is norethindrone, levonorgestrel, desogestrel, or norgestimate. Most of them also use ethinyl estradiol, which is a 100-to-250-times-stronger synthetic estrogen, as the estrogen partner.
The hormonal IUD — Mirena, Liletta, Kyleena, or Skyla — releases levonorgestrel straight into the uterus. The dose is small. But levonorgestrel is one of the more androgenic progestins. And it does not stay only in the uterus. Measurable levels reach the bloodstream, and they reach the breast.
Let's translate relative risk into real numbers. In the UK study above, the absolute extra breast cancer cases over five years of combined hormone treatment were on the order of 3 to 8 extra cases per 10,000 women per year. The number depends on which progestin is used. That is small in absolute terms. But it is not zero. And it accumulates with years of use [2].
This is one of several reasons I tend to be cautious about long-term use of the pill and the IUD. I am most cautious in women who have other reasons to protect breast tissue. A family history of breast cancer. Dense breasts. A long lifetime exposure to estrogen. A history of progestin intolerance. A previous breast biopsy with atypia.
What the standard message leaves out
The usual line — "the pill is safe, the IUD is local, the breast cancer signal is small" — is not exactly wrong. The absolute numbers are small.
But the standard message leaves out a few things.
That hormones do not stay where they are made. A pill or an IUD does not act in just one place. The synthetic molecules circulate, and they signal every cell in the body that has a receptor for them.
That not all progestins behave the same way in breast tissue.
That bioidentical progesterone is biologically different from synthetic progestins, and the risk profile of one cannot be assumed for the other.
That the breast has its own protective androgen system. The pill suppresses your own testosterone (by raising a binding protein called SHBG). And in its place, it delivers a synthetic hybrid that signals partly as an androgen and partly as an estrogen.
That the hormonal IUD delivers levonorgestrel, one of the more androgenic and estrogen-cross-reactive progestins, every day, often for years.
That the estrogen in most combined pills is 100 to 250 times more potent than your own, and is broadcasting that signal to every tissue in your body for as long as you take it.
This is not an argument that the pill or the IUD is wrong for every woman. They prevent pregnancy. They can manage heavy bleeding and ease painful periods. Those are real benefits, and many women choose these tools for good reasons.
It is an argument for knowing what you are choosing. And for asking whether a different option — bioidentical progesterone, a copper IUD, fertility awareness, a barrier method, or a different progestin family- might fit your goals and your tissue better.
A few questions can help open this conversation.
Which progestin is in this pill or IUD, and what family is it from?
Which estrogen is in this pill, and how potent is it compared with the estradiol my body makes?
Is there a bioidentical option that would meet my goals?
What is my baseline breast cancer risk, and how does this method change it in absolute numbers, not just relative ones?
If I have other reasons to protect my breast tissue — family history, dense breasts, a long history of cycles — does that change which method is right for me?
If I am using this for symptoms (heavy bleeding, painful periods, hormonal acne, perimenopausal changes), are there options that address the underlying physiology rather than override it?
You always have the right to accept, delay, or refuse a treatment. Good medical care includes clear information about how each option works in your body. It also includes respect for your right to choose what happens to your tissue.
The bottom line
The pill and the hormonal IUD contain specific synthetic molecules that travel through your bloodstream and signal cells throughout your body — your breast, your liver, your brain, your bones, your blood vessels.
The closer the molecule is to what your body makes, the more your tissues tend to recognize it and respond well. The further from your own physiology a synthetic hormone drifts — and testosterone-derived progestins drift the furthest, with ethinyl estradiol drifting 100 to 250 times louder than your own estrogen — the more off-target effects come along for the ride.
This is why I lean toward bioidentical progesterone whenever progesterone support is needed. And it is why I am cautious about long-term use of testosterone-derived progestins, and high-potency synthetic estrogens like ethinyl estradiol, in women who want to protect their breast tissue over the decades ahead.
The goal of this article is not fear, but to provide you with information that respects your physiology, your history, and your right to decide.
References
1. Africander, D., et al. (2017). https://doi.org/10.1016/j.bbrc.2017.07.063
2. Vinogradova, Y., et al. (2020). https://doi.org/10.1136/bmj.m3873
3. Fournier, A., et al. (2008). https://doi.org/10.1007/s10549-007-9523-x
4. Cordina-Duverger, E., et al. (2013). https://doi.org/10.1371/journal.pone.0078016
5. Chlebowski, R.T., et al. (2020). https://doi.org/10.1001/jama.2020.9482
6. Hickey, T.E., et al. (2021). https://doi.org/10.1038/s41591-020-01168-7
7. Carroll, J.S., et al. (2012). https://doi.org/10.1210/me.2012-1107
8. Bai, Y., et al. (2021). https://doi.org/10.3390/cancers13225635
9. Shamseddin, M., et al. (2021). https://doi.org/10.15252/emmm.202114314
10. Barbieri, R.L., et al. (1983). https://doi.org/10.1210/jcem-57-2-299
11. Gompel, A., et al. (2026). https://doi.org/10.1016/S2213-8587(25)00394-8
12. Stanczyk, F.Z., et al. (2013). https://doi.org/10.1016/j.contraception.2012.12.011
13. Kuhl, H., et al. (2005). https://doi.org/10.1080/13697130500148875
For more information on this topic, see my other articles:
Hormones & Breast Cancer: What’s Fact, What’s Fiction?
The History of Breast Cancer Treatments and the Misguided War on Estrogen
Disclaimer: This article is for educational and informational purposes only and is not intended to replace personalized medical advice or individualized care. It is meant to help you understand your physiology, explore evidence-based options, and make informed choices about your health and wellness. Healthcare should be a partnership, not a permission slip, and proactive care is just as essential as treatment. Use this information to engage in open, collaborative discussions with your provider or to make empowered decisions that align with your own values, goals, and comfort level. You are the ultimate authority on your body.