A Reader Asks: Will Estrogen Bring My Endometriosis Back?

Written by: Meredith Paci Functional Health Coach 

A reader wrote in via our anonymous form "Ask Fortify here." with a question:

Last year I had a hysterectomy with one ovary removed due to stage 3 deep infiltrating endometriosis, along with complete surgical removal of all endo including a bowel resection. I think my one ovary is hanging on for dear life trying to keep me going with hormones. I know it won't last for long. I know the importance of hormone therapy, but I am scared to death of adding estrogen back in and having any endometriosis come back. Where and when do I start hormone therapy and at what point do the benefits outweigh my risk of the endo coming back? What are my options for hormones?

This is a genuinely hard clinical question. It sits at the intersection of two bodies of evidence that don't usually get discussed together: what we know about ovarian function after surgery like this, and what we know about hormone therapy in women with an endometriosis history. I want to be incredibly thoughtful as I go through this, so that anyone this applies to, and any coach working with someone this applies to, has the information she needs. I am going to chat through this one piece at a time.

First, a word on language, because I had to infer something

The reader says "hysterectomy" and "one ovary removed." She doesn't say whether her uterus is gone. I'm inferring it is, because someone describing a same-surgery combination of "hysterectomy" plus "ovary removed" is typically describing removal of the uterus with a unilateral salpingo-oophorectomy done at the same time, and because she's asking about starting estrogen without mentioning any concern about endometrial protection, which is what a person with a uterus is told to worry about first.

I want to flag this as an inference, because it's a learning opportunity for you all reading this to which I really hope the coaches are sitting a little taller. "Hysterectomy" is an incredibly inconsistently used word. Patients/clients, and sometimes clinicians in casual conversation, use it to mean the uterus alone, the uterus and cervix, or the uterus and both tubes and ovaries. It's a systemic communication gap, and in my opinion, when we're talking about something this consequential, we should only be discussing specifics. If you are a coach working with a client who says "I had a hysterectomy," that sentence alone tells you almost nothing specific about her organ status and therefore her hormonal status. You know something was removed. That's about it. I believe you need to ask directly: was the uterus removed, were one or both ovaries removed, was the cervix removed. Don't fill in the blank with the most common scenario. Ask.

For the rest of this piece, I'm proceeding on the working assumption that her uterus is gone and, as she stated, one ovary remains. I'll note where that assumption changes the answer.

"I think my one ovary is hanging on for dear life trying to keep me going with hormones. I know it won't last for long." — the reader

What we know about living on one ovary

The best available evidence on unilateral oophorectomy alone comes from a 2021 systematic review pulling together the human and animal data on this exact question (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938940/).

Reasonably solid, consistent across three large human cohorts out of Norway, Japan, and Denmark: women who lose one ovary reach menopause earlier than women with two, roughly one to two years earlier. In animal studies, the remaining ovary appears to compensate to some degree by increasing its ovulation rate within existing follicles rather than recruiting new ones. That's a mechanism observed in rats, cattle, and sheep. So yes, it can happen, but let me be clear, and as a woman who did have one ovary removed initially, that is not a guarantee.

Pretty darn concerning (okay fine maybe this should be "Moderately" but I personally believe it should be rated higher than Moderate), replicated in more than one Mayo Clinic cohort: unilateral oophorectomy before natural menopause is associated with increased risk of cognitive impairment, dementia, and Parkinson's disease, at a magnitude the authors describe as comparable to what's seen after losing both ovaries. This is association, not proven causation. BUT it's been found more than once, and respectfully speaking, I don't find this surprising. The association is noteworthy in my humble opinion.

Important nuance the reader who wrote in needs to know: none of that data applies cleanly to her situation, because almost all of it describes unilateral oophorectomy by itself: ovary removed, uterus and other ovary left alone. She didn't have that. She had a hysterectomy at the same time as losing one ovary. That combination changes the picture substantially, and this is the piece of evidence I think she most needs to hear.

A prospective study out of Duke (the PROOF study, published in Obstetrics & Gynecology, https://pmc.ncbi.nlm.nih.gov/articles/PMC3210082/) found that hysterectomy plus unilateral oophorectomy, her exact combination, carried a hazard ratio (HR) of 2.93 for earlier ovarian failure compared to women with an intact uterus.

Her instinct isn't sound..

The real question underneath her question: will estrogen wake the endometriosis back up?

Endometriotic tissue itself expresses aromatase, meaning it can make its own local estrogen independent of anything a person takes as HRT. That's part of why recurrence after "definitive" surgery isn't fully predictable. Plainly stated: it can come back.

I want to be clear that I have never been diagnosed with endometriosis, but I was presented with a similar situation. I had surgery to remove very large dermoids on my ovaries that we believed initially could have been causing my ovarian torsions. Sadly, in less than a year post-surgery, they grew back. It was a risk I understood going in. Disappointing, of course, but not a surprise.

Here's the more reassuring part. The direct evidence we have on timing and type doesn't support the fear that estrogen replacement therapy reliably reactivates endometriosis. I'm going to walk through three studies.

1. A retrospective Johns Hopkins cohort of 95 women followed for a mean of 57 months found that 7% of women who started estrogen within 6 weeks of surgery had recurrent pain, compared with 20% of women who waited longer than 6 weeks. That gap looks large in absolute terms, roughly triple, but the sample was small (4 women vs. 7 women), and the raw comparison didn't reach statistical significance (P=.09). Once the researchers adjusted for other factors, the delayed group's risk did become significant. So: a real signal, in a study too small to be the final word on its own.
2. A larger retrospective cohort following 330 women for a median of 6 years after hysterectomy with bilateral oophorectomy for endometriosis found an overall recurrence rate of only 3%, with no meaningful difference between estrogen-only, estrogen-plus-progestogen, and tibolone, and zero cases of malignant transformation. I want to define that last term clearly, because it's not the same as recurrence: recurrence means the disease itself comes back, still benign. Malignant transformation means endometriotic tissue turns cancerous, which is rare, and a separate concern from ordinary recurrence. Worth knowing too: recurrence rates in the broader literature range much wider than 3%, anywhere from roughly 3% up to the 60% range in some cohorts, largely depending on how completely the disease was excised and whether ovarian tissue was left behind. So take that 3% as one data point, not the ceiling or the floor.
3. A Cochrane review on this exact question found the evidence isn't strong enough to justify withholding hormone therapy from women who need it.

YET, and this is where I have to be me and make sure you understand it: none of that proves estrogen is risk-free for someone with her history. It does mean the old "wait 18 months and be terrified of estrogen" teaching isn't well supported. Where the evidence lands consistently: the safer default, with any endometriosis history, is combined therapy, estrogen plus a progestogen, or tibolone, rather than estrogen alone. That holds even in someone without a uterus.

Why she may need a progestogen even though her uterus is gone

Quick clarification before this section: "progestogen" is the umbrella term. It can mean a synthetic progestin (like MPA), or it can mean oral micronized progesterone, which is body-identical. My own clinical leaning is toward suggesting oral micronized progesterone as the starting point, not a synthetic progestin, though her provider may have reasons to choose differently. I feel in her case specifically an oral micronized progesterone is most valid. 

In someone with an intact uterus, progesterone's (yes a progestin as well) primary role in HRT is endometrial protection: preventing hyperplasia, meaning abnormal tissue overgrowth, from unopposed estrogen. She has no endometrium to protect, so that specific reason doesn't apply to her.

But there are other, separate reasons to use oral micronized progesterone that have nothing to do with the uterus:

• Suppressing estrogen's proliferative effect on residual endometriotic tissue that surgery may not have fully removed. This is the one most specific to her situation.
• Sleep. This is the best-supported of the additional reasons: progesterone converts to allopregnanolone in the brain, which acts on GABA receptors, the same calming pathway benzodiazepines use, and clinical trials have shown real improvement in sleep quality with progesterone-containing HRT.
• Bone. Moderate evidence here, not as strong as sleep. A KEEPS substudy found that estrogen paired with cyclic oral micronized progesterone prevented cortical bone density decline over 4 years. It's harder to isolate progesterone's individual contribution since it's almost always studied alongside estrogen.
• Brain and mood more broadly. This one is the least settled. Progesterone receptors are present throughout the brain and the mechanism (again, allopregnanolone and GABA) is well described, but most of the neuroprotection evidence is mechanistic or animal-based rather than large human outcome trials. Promising, not proven.

The best way to frame this for her: she may be told she "doesn't need progesterone" because she has no uterus. That could potentially, maybe be partially true for the endometrial-protection reason. It may not be true for the endometriosis-suppression reason, or for these other reasons. I believe this should be an open discussion with her provider, not a closed door.

Finally, I touched on this indirectly, but for this reader this detail is very important: how complete was the excision?

The single biggest driver of recurrence isn't hormone therapy at all. It's how thoroughly the disease was excised at the time of surgery. She describes complete surgical removal of all visible endometriosis, including a bowel resection, which is a marker of a thorough, excision-focused surgery. That's incredibly positive news, but worth confirming explicitly: ask her surgeon, or read the operative report, for whether excision was macroscopically complete, whether deep infiltrating disease was fully resected at the bowel margins, and whether any disease was intentionally left behind. That single conversation will tell her more about her actual recurrence risk than anything else in this piece.

On timing

There's no evidence supporting the old "wait 18 months" convention. Her remaining ovary may still be producing meaningful estrogen right now, which is a reason for calm rather than urgency. But the PROOF data above is a reason not to be complacent about waiting for lab-confirmed failure before having this conversation. Checking FSH and estradiol now, even without symptoms, gives her and her provider real information instead of a guess. Respectfully running FULL labs would be warranted regardless.

I go through this in much more depth in our Master Class, Coaching Through Perimenopause: Raising the Standard, available as part of Fortify Core membership (along with our other educational materials, free community, and quarterly live Zoom sessions) or for individual purchase [HERE]. You can become a Fortify Core member [HERE].

Back to her...

The data does not clearly back the idea that estrogen use itself reliably drives recurrence, particularly when it's paired with a progestogen and when excision was thorough.

Some questions, and maybe a statement, for her to bring to her provider:

"Hi, I am wanting to be proactive about my overall health. I would like to pursue hormone replacement therapy."

1. What does my operative report say about completeness of excision, and were there any known residual areas?
2. What does my current FSH, LH, total and free testosterone, progesterone, and estradiol look like? Can we run complete labs to assess my full metabolic health as well? I'd also like to discuss getting a Bone Mineral Density test.
3. Given my history, would you start me on combined estrogen-progestogen rather than progesterone or estrogen alone, and why?
4. Understanding there are multiple routes available for testosterone, progesterone, and estradiol [see my previous blog on this HERE], what route would you recommend for me, given my history and current status?

To the reader who submitted this amazing question....THANK YOU! Hoping this and previous blogs helps you have a meaningful and informed conversation advocating for your health. 

If you want support working through decisions like this one for yourself or for a client, that's exactly what our mentorship and 1:1 strategy sessions are for. You can learn more about mentorship [here], or book a 1:1 strategy session [here].

If you have a question of your own, the anonymous form that started this entire series is still open. Ask Fortify here. I already have the next one queued up and I cannot wait to get into it!

Meredith Paci is the co-founder of Fortify Health Coaching. I want to be clear that I'm not a licensed medical provider. The content in this post is educational and does not constitute medical advice or a patient-provider relationship. If you are considering hormone therapy, work with a qualified and well experienced provider who will assess your individual history.