"1 in 5 women on pellets developed this. Were you told?"

Okay, so here’s a number that stopped me cold.

In a published study of postmenopausal women on hormone pellet therapy, 20.4% developed endometrial hyperplasia — an abnormal thickening of the uterine lining that is, depending on type, a direct precursor to uterine cancer. (Filho et al., Gynecological Endocrinology, 2007)

One in five.

And here’s what makes that number even more alarming: the researchers compared their results to studies using “continuous estrogen/progestin regimens” — and noted their hyperplasia rates were higher. Meaning the pellet patients weren’t getting the same protective coverage as women on standard oral hormone therapy.

Whether those women were on progesterone at all — the abstract doesn’t say. The silence on that point might be the loudest thing in the paper.

I want to walk you through exactly what’s happening here, because this is a case where the biology is fascinating, the problem is fixable, and the stakes are legitimately high.

First: What Is Your Uterus Actually Worried About?

Your uterine lining — the endometrium — responds to estrogen by thickening. That’s its job. In your reproductive years, progesterone comes in after ovulation and tells it to stop proliferating, mature, and either support a pregnancy or shed cleanly as a period.

After menopause, if you’re taking estrogen, that thickening signal is still on. Without adequate progesterone to oppose it, the endometrium can just… keep growing. Sometimes that growth is chaotic and disorganized. That’s endometrial hyperplasia.

There are four types of endometrial hyperplasia, and their cancer risk is very different:

Simple without atypia: ~1% progression to cancer (relatively benign)
Complex without atypia: ~3% progression
Simple with atypia: ~8% progression
Complex with atypia: ~29% progression to cancer — and here’s the kicker: when women with atypical hyperplasia go to surgery, somewhere between 34% and 50% already have concurrent endometrial cancer that wasn’t yet diagnosed. (StatPearls NBK560693; PMC10930610)

Part of why that number is so high comes down to the biopsy tools themselves. The Pipelle device — the standard office endometrial biopsy instrument — samples only approximately 4% of the endometrial surface, and D&C (dilation and curettage), the more invasive option, still leaves more than half the uterine cavity unsampled in roughly 60% of procedures. Cancer tends to grow in the corners and crevices the instrument can’t reach. A “normal” biopsy doesn’t mean nothing is there; it means nothing was found in the 4% that got sampled.

Atypical hyperplasia is not a “watch and wait” situation. It’s a “get this handled now” situation.

Why Pellet Progesterone Is a Pharmacokinetics Problem

Okay so this is where the biology gets really interesting — and also where you might feel a little betrayed if you’re currently on pellets.

Progesterone is a notoriously finicky molecule when it comes to delivery. It’s one of the most studied hormones in all of medicine, and one clear thing the research shows: how you deliver it matters enormously.

Oral micronized progesterone (think Prometrium, or compounded OMP) works well for endometrial protection because it passes through the gut, gets absorbed, processes through the liver, and produces metabolites that hit the uterine lining with enough concentration to do the job.

Subcutaneous progesterone pellets have a fundamental problem: the hormone gets absorbed from the fat layer and releases slowly into systemic circulation — but it does not achieve the serum levels needed to protect the endometrium.

Here’s the number that matters: studies show that a 600mg progesterone pellet implant (six pellets at 100mg each) produces mean serum progesterone levels of approximately 3 ng/mL. And it’s generally established that you need at least 5 ng/mL to inhibit endometrial cell division and induce the secretory changes that mean the uterus is actually protected. (Pharmacokinetics of progesterone data; Greenblatt & Hair, J Clin Endocrinol Metab, 1945 — yes, we’ve known this since 1945)

Think of it like flood insurance. You paid for it. You have the policy. But someone quietly wrote in the fine print that it doesn’t cover water damage from estrogen. You’re only covered when progesterone levels are above 5. Yours are at 3.

This isn’t just a pellet-specific concern. Research on progesterone creams and gels — which have the same subcutaneous/transdermal absorption problem — found the same thing:

“The current evidence has failed to show any endometrial protection from progesterone creams or gels.” — Newson & Rymer, British Journal of General Practice, 2019

The route is the problem. Your skin and your fat tissue absorb progesterone, but they don’t reliably pass it to the uterus at the concentrations needed for protection.

The BioTE Admission (This Is the Part That’s Wild)

BioTE is the largest pellet franchise in the United States. They’ve trained thousands of providers. They have a published protocol — and it explicitly states, in their own words:

“All patients started on estrogen with a uterus must receive progesterone to protect the uterus.”

Their recommended starting dose: 225 mg of compounded oral micronized progesterone, taken nightly.

They even warn against using a standard pharmacy Prometrium: “if you write a generic prescription for 200mg progesterone for your local pharmacy, it can vary by 30% and that variation… may lead to a withdrawal bleed.” They want you on specifically compounded 225mg OMP, taken by mouth, every night.

Read that again: the largest pellet company in the country requires you to take a nightly oral pill because the pellet alone doesn’t protect your uterus.

They know the subcutaneous route is insufficient. It’s written into their own protocol.

So the question becomes: how many of their licensed providers are actually following that protocol?

What “20.4% Despite Progestin Use” Tells Us About What’s Actually Happening

Back to the Filho 2007 study. Let me give you the full context.

258 postmenopausal women were on estradiol + testosterone pellets for two years. Of those with endometrial thickening detected on ultrasound, 20.4% had developed hyperplasia.

The researchers specifically noted these rates were higher than what studies using continuous combined estrogen/progestin regimens typically showed.

The authors concluded that “the use of progestins as the ideal endometrial protection should be reconsidered” — a remarkable statement suggesting either the progestin wasn’t being prescribed, or it wasn’t working as expected.

This is a retrospective chart review. It’s not a controlled trial. But it’s real-world clinical data from a pellet-using population. And the signal is not subtle.

The Menopause Society has been direct about what this means:

“The Menopause Society strongly discourages the use of compounded products, especially pellets, due to increased risk of endometrial hyperplasia or cancer, especially when progesterone is not adequately prescribed with estrogen.”

In November 2023, ACOG (American College of Obstetricians and Gynecologists) published Clinical Consensus No. 6 on compounded bioidentical hormone therapy. Their conclusion on pellets: given the “lack of safety data and inability to remove the pellet,” ACOG recommends “preparations other than pellet therapy.” (PMID: 37856860)

You cannot un-insert a pellet if something goes wrong. That’s not a small problem.

Are YOU at Risk? A Quick Self-Assessment

This matters to you if ALL of these are true:

1. Do you have a uterus? (If you’ve had a hysterectomy, you don’t have an endometrium to worry about — estrogen unopposed by progesterone is actually fine for you.)

2. Are you on estrogen pellets? (Testosterone-only pellets are a different conversation. Estrogen pellets are the issue here.)

3. Are you also taking oral micronized progesterone EVERY NIGHT? Either prescribed Prometrium (100mg or 200mg), or compounded OMP 225mg as BioTE’s protocol requires?

If you answered yes to #1 and #2, but NO to #3 — or if you’re not sure — that’s the conversation you need to have with your provider. Today.

What about progesterone creams or gels? As covered above: insufficient for endometrial protection. Don’t let anyone substitute these for oral OMP.

What about the Mirena IUD? Actually yes — a Mirena IUD releases levonorgestrel (a progestin) locally in the uterus and provides excellent endometrial protection. Some providers use Mirena + pellets as a protocol. For complex hyperplasia without atypia, Mirena shows 92% regression rates vs. 66% with oral progestins. It’s a legitimate option, especially for women who can’t tolerate oral progesterone. (AAFP, 2021)

What to Do Right Now

Step 1: Figure out your OMP status. If you’re on estrogen pellets and you have a uterus, ask your provider directly: “What oral progesterone am I on, at what dose, and how often?” If the answer is “you’re not on any” or “just a cream” — that’s a problem to solve immediately.

Step 2: Request a transvaginal ultrasound. This is the first-line screening tool. In postmenopausal women, an endometrial stripe measurement above 4–5mm warrants further workup. This is a quick, non-invasive office procedure. If you haven’t had one since starting pellet therapy and you have a uterus, ask for one.

Step 3: If your ultrasound shows thickening, get an endometrial biopsy. A pipelle biopsy is an office procedure (no sedation required for most women) that samples the endometrial lining and identifies hyperplasia type. Non-atypical forms are manageable conservatively. Atypical forms need prompt treatment. Don’t wait.

Step 4: Understand your options if hyperplasia is found.

Hyperplasia without atypia: high-dose oral progestins OR Mirena IUD, with follow-up biopsies every 6 months until two consecutive clear results
Atypical hyperplasia: Mirena IUD for women who want to preserve fertility; hysterectomy is the definitive treatment for women who don’t — because the concurrent cancer risk (up to 50%) is too high to manage conservatively

This Is Not Anti-Pellet

I want to be clear: this is not about telling you that pellets are evil and you should throw them in the trash.

Plenty of women do very well on pellet therapy. The steady hormone release — no peaks and troughs — genuinely works for many people. Some providers do follow the BioTE protocol to the letter and co-prescribe OMP meticulously. If that’s you, great.

This is about uninformed pellet use. It’s about the gap between what the protocol says and what real-world practice often delivers. It’s about the fact that 20.4% in a published study developed hyperplasia — and that number gets a whole lot more concerning if the oral progesterone piece was being skipped.

The uterus is not an optional organ in your hormone therapy protocol. If you have one, your estrogen needs to be opposed by adequate, bioavailable progesterone. That means oral OMP every night, or a Mirena IUD in place.

Your pellet provider owes you that conversation. If they haven’t had it with you, go have it yourself — armed with this.

Sources:

Filho AMB et al. “Effects of subdermal implants of estradiol and testosterone on the endometrium of postmenopausal women.” Gynecol Endocrinol. 2007;23(9):511–517. PMID 17943546
ACOG Clinical Consensus No. 6. “Compounded Bioidentical Menopausal Hormone Therapy.” Obstet Gynecol. November 2023. PMID 37856860
BioTE Method Protocol. “Sub-Cutaneous Hormone Pellet Therapy.” biote.com
Stanczyk FZ, Paulson RJ, Roy S. “Percutaneous administration of progesterone: blood levels and endometrial protection.” Menopause. 2005;12(2):232–237. PMID 15772572
Newson L, Rymer J. “The dangers of compounded bioidentical hormone replacement therapy.” Br J Gen Pract. 2019;69(688):540–541. PMID 31672802
Furness S et al. “Hormone therapy in postmenopausal women and risk of endometrial hyperplasia.” Cochrane Database Syst Rev. 2012;(8):CD000402. PMC7039145
StatPearls. “Endometrial Hyperplasia.” NCBI Bookshelf NBK560693. ncbi.nlm.nih.gov
AAFP. “Levonorgestrel-Releasing Intrauterine System for Regression of Endometrial Hyperplasia.” Am Fam Physician. 2021. aafp.org
Subcutaneous Estradiol Pellets review. J Clin Med. 2026;15(1):48. mdpi.com
PMC Compounded Hormonal Pellets Critical Review. PMC12341420. pmc.ncbi.nlm.nih.gov

Annette Thompson is 57, the founder of adoption.com, and a menopause advocate writing about evidence-based women’s health.