Progestin vs progesterone: why the difference matters

The terms, sorted out

Progestins were developed partly because natural progesterone was poorly absorbed by mouth until micronization, a process that creates very fine particles, made oral progesterone practical.

• Progesterone: the natural hormone produced by the ovaries after ovulation, also available as micronized progesterone capsules
• Progestins: synthetic molecules designed to activate progesterone receptors, such as medroxyprogesterone acetate, norethindrone and levonorgestrel
• Progestogen: the umbrella term for anything with progesterone-like action, natural or synthetic

Why a progestogen is needed at all

If you have a uterus, estrogen alone stimulates the lining to grow, which raises the risk of endometrial hyperplasia and cancer. FDA has kept its boxed warning about endometrial cancer for systemic estrogen-alone products for this reason. Adding a progestogen counteracts that growth. The FDA-approved micronized progesterone label specifically covers preventing endometrial hyperplasia in postmenopausal women with a uterus who take estrogen.

Women without a uterus generally do not need a progestogen when they take estrogen.

How progestins differ from progesterone

Different progestins have different side activities. Some have androgen-like effects that can affect cholesterol, skin or mood. Others interact with receptors involved in fluid balance. Natural progesterone has its own profile: it is often sedating, which is why it is taken at bedtime, and it can cause dizziness in some women.

These differences can shape which one suits you, particularly if you have had side effects such as mood changes, bloating or breast tenderness on one type.

What the WHI tested

The Women's Health Initiative enrolled more than 68,000 postmenopausal women aged 50 to 79. Its combined hormone arm used conjugated equine estrogens with a specific synthetic progestin, medroxyprogesterone acetate, and found a small increase in breast cancer. The estrogen-alone arm, in women who had had a hysterectomy, did not show the same increase.

Because only one estrogen-progestin combination was tested, the WHI could not say whether other combinations, including micronized progesterone, carry the same risk. Participants were also older on average than women who typically start hormone therapy today.

What later evidence suggests

The French E3N cohort study followed a large group of women using different hormone combinations. Women using estrogen with progesterone had no significant increase in breast cancer risk compared with never-users, while those using estrogen with other synthetic progestins had a significantly higher risk. The Menopause Society notes that intermittent micronized progesterone may be associated with lower combined-therapy risk.

This is observational evidence, not randomized trial data, and it does not show zero risk. Women who chose different products may have differed in other ways. Still, it is one reason many clinicians prefer micronized progesterone when it suits the patient.

Where progestins remain the right choice

The goal is reliable protection of the lining with side effects you can live with. That can be achieved with either type.

• A levonorgestrel intrauterine device provides strong local protection of the lining with little effect elsewhere, and also provides contraception in perimenopause
• Women who become very drowsy or dizzy on progesterone, or who have a peanut allergy (oral micronized progesterone capsules contain peanut oil)
• Specific gynecologic conditions, such as some cases of heavy bleeding or endometriosis
• Combined patches or tablets that some women find more convenient

Questions to ask about your progestogen

Clear answers help you understand what you are taking and why, and they make it easier to raise problems early.

• Is my prescription progesterone or a synthetic progestin?
• Is it FDA-approved or compounded?
• Is my regimen cyclic or continuous, and what bleeding should I expect?
• What should I do if I feel very drowsy or notice mood changes?
• How will we know my uterine lining is protected?

What HealifyMD uses

When endometrial protection is needed, HealifyMD clinicians generally use oral micronized progesterone. Some progesterone in the plan is compounded; compounded progesterone is not FDA-approved and is not equivalent to branded products such as Prometrium. Your clinician will explain the options, including FDA-approved alternatives.

HealifyMD's hormone therapy plan for women is $349 for the first month (including the evaluation and baseline labs), then $99/month, with estradiol, estriol vaginal cream and progesterone included in the hormone therapy program. Compounded hormones are not FDA-approved and are not equivalent to branded products. Other labs are priced separately, and your price is confirmed at the eligibility review.