What Are SERMs? What’s Atrophy? What’s Ospemifene?
We’ll start with an overview:
SERMs are Selective Estrogen Receptor Modulators. They change how the body responds to circulating estrogen by turning estrogen receptors on and off in specific parts of the body.
Content note: we use anatomical words to describe body parts in this blog. In the context of this blog, “genital tissue” refers to the vagina and vulva.
Does scientific language fell overwhelming? We wrote a primer on how to read medical journal articles.
Table of Contents
- What Are Some Common SERMs?
- What is Ospemifene?
- What is Atrophy?
- Are Recurrent Urinary Tract Infections Something To Worry About?
- Why Not Locally Applied Estrogen Or Other Common Treatment Options?
- What Forms Does Localized Estrogen Come In?
- Why Might Local Estrogens Not Be A Good Choice For Me?
- What Are Some Medical Reasons To Not Use Low-Dose Local Estrogen?
- How Does Ospemifene Compare to Local Estrogen Use?
- What Do The Studies Say About What Ospemifene Does?
- How Does Ospemifene Work?
- What Are The Known Side Effects of Ospemifene?
- What Do We Know About Risks For Other Diseases While Taking Ospemifene?
- Would Ospemifene Be A Good Choice For Me?
- What Does Ospemifene Cost?
- Related Articles In The QueerDoc Blogosphere
- References and Citations
What Are Some Common SERMs?
We use raloxifene in gender affirming care the most often, and very rarely use tamoxifen. We use raloxifene to suppress breast growth while taking estradiol or to reduce already developed breast tissue. Tamoxifen can occasionally be used similarly.
Each SERM targets estrogen receptors in different parts of the body or in different ways. Raloxifene deactivates estrogen receptors in the breasts while activating them in other areas. Tamoxifen attaches to estrogen receptors in breast tissue.
What is Ospemifene?
Ospemifene is a relatively new SERM that targets receptors in genital tissues. It may be a good choice for people taking testosterone or have atrophy due to peri-menopause, menopause, and post-menopausal changes.
Ospemifene is a tablet taken by mouth once a day with a meal (preferably one with some fat in it.)
What is Atrophy?
“Atrophy” is a medical term that describes body tissues that get smaller, become less full or developed, or lose function. It can also describe processes in the body not working as well as they used to. An example is muscle atrophy when someone has been in a cast – the muscles get smaller and weaker over time! For today, we’ll use it to describe changes that happen in genital tissues when estrogen levels are lower or when testosterone levels are higher. When this happens during peri-menopause and menopause, it is called genitourinary syndrome of menopause (GSM). We wrote about the treatment of GSM in our article about gender affirming peri-menopausal and menopausal care.
For people experiencing atrophy, it can mean symptoms like:
- Dryness, or less body-made lubrication
- Burning sensations
- Irritation
- Pain with genital receptive practices or sexual activities
- Urinary urgency
- Recurrent urinary tract infections* (see our special note below)
- Change in genital tissue pH towards a less-acidic environment
- Pelvic discomfort
- Changes in genital tissue size, shape, fullness, and elasticity.
Common treatment options include local estrogen therapy, moisturizers like Replens or Good Clean Love, lubricants and pelvic floor physical therapy. Ospemifene is an option for people for whom taking estrogen alone or in combination with other approaches is not sufficient – or isn’t wanted!
Resource: Smitten Kitten’s 2015 guide to lubes for low-estrogen genital tissues. (It’s an older guide, but still among the best resources we’ve seen!) If you’re interested in getting really nerdy about lubes, Smitten Kitten also published Lube! An In-Depth Look At Personal Lubricants.
*Are Recurrent Urinary Tract Infections Something To Worry About?
They’re a big deal! Not only are UTIs uncomfortable (or absolutely painful,) and inconvenient, they can lead to very serious health issues such as kidney infections and sepsis, and are linked to higher rates of morbidity (lowered quality of life) and mortality (death) in older adults.
Available evidence suggests that treating atrophy can help prevent UTIs, increase quality of life and lower the potential risks associated with frequent or recurrent UTIs. A study of more than 5600 postmenopausal cis women who had frequent UTIs found that treatment with localized estrogen cut the number of UTIs they had in half. (Tan-Kim)
A 2026 study of nearly 2 million women aged 20 – 99 with recurrent UTIs found that local estrogen use meant less sepsis, fewer hospitalizations, and fewer deaths within 8 years. These results were particularly strong in younger individuals. That’s incredible! It may be that in the next few years we’ll see movement towards recommending local estrogen use for people of all ages who have recurrent UTIs. (LaClair)
Learn more about urinary tract infections (UTIs) with the CDC’s overview of symptoms, risk factors, diagnosis, treatment, and prevention for non-medical people.
Why Not Locally Applied Estrogen Or Other Common Treatment Options?
Locally applied estradiol is considered the preferred and first-to-try treatment for symptoms of genitourinary atrophy, and we’ll typically recommend trying it if you want to treat symptoms of atrophy. It’s considered to be pretty effective and generally safe. Here’s our blog dedicated to direct contact, localized estrogen use.
The National Menopause Society’s 2020 policy states that although the package inserts for locally applied estrogens contain the same warnings as those for systemic (affecting the whole body) estradiol, the studies to date indicate that low-dose local estrogen does not increase the risk of bad health outcomes including cardiovascular disease, hip fracture, or several cancers, including total invasive, breast, endometrial, ovarian, and colorectal. Their “Meno Note” dives into treatment options for genitourinary syndrome of menopause.
What Forms Does Localized Estrogen Come In?
- Creams
- Rings
- Tablets
- Soft gels
Why Might Local Estrogens Not Be A Good Choice For Me?
- Dysphoria with application.
- Physical difficulty with application.
- Hard to remember scheduling (creams and tablets are often twice a week).
- Cleaning those applicators is a PITA! Or maybe you just want less plastic in your life.
- Reactions to inactive ingredients.
Localized estrogens are generally inexpensive. Compounded forms can be more expensive. Pricing of creams or tables from our mail order pharmacy partner is typically just a few dollars a month.
What Are Some Medical Reasons To Avoid Low-Dose Local Estrogen?
People who are experiencing unexplained genital bleeding should not use localized estrogen on the genitals. People who are diagnosed with estrogen-dependent cancers should discuss using localized estrogen with their oncologist.
OK, So What About Ospemifene?
How Does Ospemifene Compare to Local Estrogen Use?
For much of this article, references to studies come from a 2024 meta-analysis of 25 studies. (Di Carlo) A meta-analysis is a combined review of several published articles on a single scientific topic. It is considered to be a very good way to determine what the overall body of evidence supports. If we refer to something from a different study, we’ll add a reference.
A BIG NOTE ABOUT STUDIES FOCUSING ON TRANS FOLKS:
There are no studies of this medication in trans people, and the studies we do have are in post-menopausal cis women aged 40 to 80. We do not have any studies about use in younger people or people who may have atrophy associated with testosterone use.
A 2017 study compared studies of estradiol efficacy (how well the treatment worked) compared to placebo and how ospemifene worked compared to placebo. In studies with placebos, the participants don’t know if they are receiving the medication or not. Placebo studies can help figure out if the treatment is better than doing nothing. We didn’t find any studies comparing estradiol to ospemifene directly.
This study found no meaningful differences between localized estrogen and ospemifene use for how well they worked, and the study found that safety and tolerability (ease of use) are similar between the two. However, while localized estrogens are typically recommended to be used for the shortest time possible, there is no similar recommendation on limiting how long someone uses ospemifene. There’s no time limit on using ospemifene! (Climacteric, 2017.)
A Spanish study of 752 individuals found that people taking ospemifene were happier with the treatment than those using estrogen or using a moisturizer. They also reported lower numbers of missed or skipped doses. They reported better quality of life than the moisturizer users.
What Do Other Studies on Ospemifene Say?
Clinical trials in post-menopausal people experiencing painful penetration and/or genital dryness found that they had less pain and discomfort after 12 weeks of taking ospemifene compared to people taking a placebo for 12 weeks. Those studies found meaningful improvements pain and in symptoms of atrophy including healthier tissue pH and the balance of micro-organisms in the genital tissues. Multiple studies also found improvements in dryness.
The meta-analysis of 25 clinical studies that we mentioned earlier (Di Carlo) found that taking ospemifene:
- improved symptoms by 12 weeks, with sustained improvement at 52 weeks.
- promoted healthier, more resilient (more collagen content), and fuller genital tissues.
- resulted in a return of tissue pH to more acidic levels associated with pre-menopausal (or, we presume, pre-T) levels.
- decreased pain with receptive sexual practices.
- decreased vulvar symptoms and pain.
- reduced symptoms of overactive bladder, how many times people urinated in 24 hours, urgency in the need to pee, and the ability to control peeing.
- may support increased frequency of sexual activity in those who want to have more sexual activity.
The Short Answer:
Ospemifene appears to increase lubrication and decrease the pain and discomfort associated with atrophy. Genital tissues after using ospemifene are healthier and more like pre-menopausal tissues after using ospemifene.
How Does Ospemifene Work?
Ospemifene increases estrogen-like activity in genital tissue and in bone tissue.
🡆These tissues appear to benefit from this increased activity.
🡆 It may help protect against osteoporosis.
🡆 It may act like estrogen in the uterus.
🡆 This has unclear impacts on how your uterus might behave. No significant negative impacts were identified.
🡆 It doesn’t appear to affect breast or bone tissue.
What Are The Known Side Effects of Ospemifene?
Side effect differences between participants in a 52-week clinical trial of ospemifene vs. placebo:
| Side Effect | People taking ospemifene | People taking a placebo |
|---|---|---|
| hot flashes | 12.2% | 4.2% |
| muscle spasms | 4.5% | 2.4% |
| excessive sweating | 2.5% | 1.8% |
| night sweats | 1.2% | 0.0% |
| headaches | 2.8% | 2.4% |
| discharge | 6.0% | 0.6% |
| bleeding | 1.3% | 0.0% |
No serious adverse events (really bad side effects) were reported.
7.6% of people taking this mediation in a year-long study stopped due to experiencing side effects. Most of those side effects were self-reported as mild to moderate and happened in the first 12 weeks of treatment.
What Do We Know About Risks For Other Diseases While Taking Ospemifene?
Cardiovascular Disease Risk
A 12-week study showed no significant difference in headaches, deep vein thrombosis (DVT), coronary heart disease, or cerebrovascular events (like stroke) between the individuals taking ospemifene and those taking placebo.
A study of 9000 individuals comparing those taking ospemifene to other SERMs after five years found no increased risk of blood clots in people taking ospemifene compared to those on a different SERM or not on a SERM.
A 15- month clinical study found a lowered risk of blood clots blocking an artery (thromboembolic stroke) compared to placebo and a raised risk of strokes where a blood vessel bursts (hemorrhagic stroke) compared to placebo. It was not determined that ospemifene caused the higher risk of burst blood vessels.
| blood clot strokes | burst vessel strokes | DVT(clots in a vein, usually a leg) | |
|---|---|---|---|
| taking ospemifene (about 1450 people) | 1 person in the study | 3 people in the study | 2 people in the study |
| taking a placebo (about 1140 people) | 3 people in the study | no one in the study | 1 person in the study |
What Is The Impact on Heart Disease and Metabolic Markers? (blood pressure, cholesterol, c-reactive protein, blood coagulation markers)
A small study of 57 women found:
- a decrease in blood pressure readings from 128/76 to 120/70 at 12 months of use.
- Cholesterol, C-reactive (a measure of inflammation) and coagulation proteins were significantly improved at 3 and 12 months:
- Total cholesterol lowered by about 8 points at 12 months.
- C-reactive protein showed less inflammation in the body 12 months.
- Two coagulation (blood clotting) markers were improved at 12 months.
No impact was seen on triglycerides, blood glucose or insulin.
An analysis of 5 randomized controlled studies including 2166 peole taking ospemifene found:
- increases in HDL (the good cholesterol)
- decreases in LDL (the bad cholesterol)
- significantly reduced total cholesterol. (Shin)
Endometrial Impact (What Does Ospemifene Do In The Uterus?)
The endometrium is the lining of the uterus. It has a high level of estrogen receptors, and studies have shown that exposure to systemic (not local) estrogen (if not balanced by adding in progesterone) after menopause can increase the risk of abnormal bleeding, hyperplasia (abnormal growth of the endometrium) and endometrial cancer.
The meta-analysis we’re referring to in this article notes that results from the randomized controlled trials showed that there were no significant negative effects of ospemifene on the endometrium. No cases of cancer were found.
Ospemifene does appear to increase endometrial thickness and the number of cells in the uterine lining, but the authors of the meta-analysis wrote that this increase is not clinically relevant (meaning that it isn’t concerning or in need of work-up). They state that there was “no statistically significant difference between the two groups…concerning the incidence of bleeding, endometrial cancer, breast tenderness, and breast and endometrial cancer.” (Di Carlo)
| Endometrial thickening | Proliferative (growing or increasing in number) endometrial cells | |
|---|---|---|
| ospemifene | 101.4 per thousand women | 26.3 per thousand women |
| placebo | 20.9 per thousand women | 0 per thousand women |
Breast Cancer Risk:
There haven’t been enough studies to indicate if ospemifene increases breast cancer cases or risk. The studies to date found no increased risk of breast cancer in individuals taking ospemifene.
What About Bone Metabolism and Osteoporosis?
In a 12-month study, there was no significant change to bone health markers between those taking ospemifene and those taking a placebo.
Precautions for Taking Ospemifene
The body processes ospemifene in the liver. We recommend carefully considering the combined impact to the liver if you have liver disease or who take other medications that also are processed in the liver.
The FDA recommends that ospemifene:
🡆 should not be taken if you’re also taking estrogen or other SERMs.
🡆 should be taken carefully when the patient is also using the below medications as they are metabolized using the same enzymes:
🡆 fluconazole (treats yeast and fungal infections)
🡆 rifampin (treats tuberculosis and meningitis)
🡆 ketoconazole (treats fungal infections)
🡆 warfarin (prevents deep vein thrombosis, pulmonary embolism, and stroke)
A more complete list of interactions between ospemifene and other meds is at drugs.com.
Would Ospemifene Be A Good Choice For Me?
| Possible Pros | Possible Cons | May Be A Good Fit If… |
|---|---|---|
| Targets genital tissues | Not an estrogen: it will not promote systemic estrogenic effects. | You don’t want to add estrogen to your body or don’t want a SERM that affects breast tissues. |
| An oral tablet | To be taken daily with a meal (a fatty meal is recommended) | Your dysphoria or sensory issues don’t allow use of local estradiol which has more evidence and safety data!. |
| Decreased pain, irritation, burning, or other genital symptoms | Most frequently reported side effects were hot flashes and increased discharge. | Genital tissue pain is interfering with your life, or local estrogen hasn’t helped enough |
| Appears to have low impact on cardiovascular or breast cancer risk. | May increase thickness in the uterine lining – but has not been shown to increase the risk of endometrial cancer. | You do not have other risk factors for endometrial cancer, or are comfortable with the likely low risk of endometrial cancer associated with thickened endometrium. |
| Risk of serious events are lower than taking systemic estrogen. | You take other medications that pass through your liver or have other liver disease risks. | A daily pill fits into your routine or you do not want to use localized estrogen (or you have tried it and it hasn’t worked for you.) Ospemifene may also be a good option if you have been advised not to use local estrogen by your doctor (although local estrogen is generally safe). |
Things to Think About
Early studies indicated that ospemifene may increase your risk of some cardiovascular diseases compared to placebo. However, the increased risk appears to be lower than taking estrogen, and more recent studies and the 2024 meta-analysis showed that ospemifene had no negative effects on cholesterol levels and may help improve cholesterol profiles.
It may also increase the thickness of your endometrium (the lining of the uterus.) This can be a risk factor for endometrial cancer, however, no cases of endometrial cancer were found in the study groups, and the meta-analysis supports the conclusion that ospemifene does not increase the risk of endometrial cancers.
What Does Ospemifene Cost?
Insurance may or may not cover ospemifene.
The manufacturer of ospemifene offers a patient assistance co-pay program for individuals with commercial insurance to help cover the cost of care.
The GoodRx.com price for a 90-day supply of brand name ospemifene in Seattle is about $200.
Related Articles In The QueerDoc Blogosphere
- How Should I Take Testosterone? Comparing Every Route of Testosterone Administration for Gender Affirming Care
- How Should I Take Estradiol? Comparing Every Route of Estrogen Administration for Gender Affirming Care
- RALOXIFENE VS. PUBERTY BLOCKERS FOR UNWANTED BREAST DEVELOPMENT IN ADOLESCENTS WITH OVARIES
- Bicalutamide vs. Puberty Blockers in Adolescents
- Gettin’ Nerdy About Gettin’ Curvy
- Transdermal Testosterone: Everything You Need to Know
- What You Need To Know Before Starting Testosterone
- Testosterone And You: Gettin’ Square, The QueerDoc Way
- Stop Aunt Flo! Menstrual Suppression 12/2024
References and Citations
FDA Prescribing Information (https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/203505s015lbl.pdf) Accessed 7/11/26
https://medlineplus.gov/druginfo/meds/a613039.html
https://www.mayoclinic.org/drugs-supplements/ospemifene-oral-route/description/drg-20060852
https://go.drugbank.com/drugs/DB04938
Costantino DiCarlo, Angelo Cagnacci, Filippo Murina, Silvia Maffei, Angelamaria Becorpi & Stefano Lello (2024) Ospemifene and vulvovaginal atrophy: an update of the clinical profile for post-menopausal women, Expert Opinion on Pharmacotherapy, 25:11, 1541-1554, DOI: 10.1080/14656566.2024.2391009
Ospemifene (Osphena): CADTH Reimbursement Recommendation: Indication: In postmenopausal women for the treatment of moderate to severe dyspareunia and/or vaginal dryness, symptoms of vulvar and vaginal atrophy, a component of genitourinary syndrome of menopause [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2022 Jun. Available from: https://www.ncbi.nlm.nih.gov/books/NBK603626/
Bondi C, Ferrero S, Scala C, Tafi E, Racca A, Venturini PL, Leone Roberti Maggiore U. Pharmacokinetics, pharmacodynamics and clinical efficacy of ospemifene for the treatment of dyspareunia and genitourinary syndrome of menopause. Expert Opin Drug Metab Toxicol. 2016 Oct;12(10):1233-46. doi: 10.1080/17425255.2016.1218847. Epub 2016 Aug 9. PMID: 27476551.
Shin JJ, Kim SK, Lee JR, Suh CS. Ospemifene: A Novel Option for the Treatment of Vulvovaginal Atrophy. J Menopausal Med. 2017 Aug;23(2):79-84. doi: 10.6118/jmm.2017.23.2.79. Epub 2017 Aug 31. PMID: 28951854; PMCID: PMC5606913.
LaClair J, Visingardi J, Wells B, Feustel P, Deckert J, De EJB. Vaginal Estrogen Prescription is Associated with Reduced Risk of Serious Adverse Outcomes in Women of All Age Groups with Recurrent Urinary Tract Infection: An Epic Cosmos Database Analysis. Urology. 2026 Jun 10:S0090-4295(26)00358-4. doi: 10.1016/j.urology.2026.06.004. Epub ahead of print. PMID: 42269780.
Tan-Kim J, Shah NM, Do D, Menefee SA. Efficacy of vaginal estrogen for recurrent urinary tract infection prevention in hypoestrogenic women. Am J Obstet Gynecol. 2023 Aug;229(2):143.e1-143.e9. doi: 10.1016/j.ajog.2023.05.002. Epub 2023 May 11. PMID: 37178856.
Donders, G. G. G., Akinosoglou, K., Massie, Z., & Özçelik, A. S. (2025). Review of current and emerging estrogen receptor agonists for vaginal atrophy. Expert Opinion on Pharmacotherapy, 26(3), 249–255. https://doi.org/10.1080/14656566.2025.2451150
Menopause: The Journal of The North American Menopause Society, Vol. 27, No. 9, pp. 976-992
DOI: 10.1097/GME.0000000000001609 2020 by The North American Menopause Society