What Are the Potential Side Effects of Hormone Replacement Therapy?

Hormone replacement therapy (HRT) can provide meaningful relief from symptoms caused by hormonal changes or deficiencies, but like any medical treatment, it can also cause side effects.

The potential side effects depend on several factors, including which hormone is being used, the dose, how it is administered, your age, your medical history, and your individual response to treatment.

For women, hormone therapy may involve estrogen, progesterone, or a combination of hormones. For men with appropriately diagnosed testosterone deficiency, treatment may involve testosterone replacement therapy.

Many side effects are mild and manageable. More serious complications are less common but are important to understand before beginning treatment.

If you are new to hormone therapy, you may also want to read our complete guide to hormone replacement therapy.

What Are the Most Common Side Effects of HRT?

Common side effects of menopausal hormone therapy can include:

• Breast tenderness

• Bloating

• Fluid retention

• Headaches

• Nausea or stomach discomfort

• Mood changes

• Changes in vaginal bleeding

• Changes in menstrual patterns during perimenopause

• Skin irritation from patches or topical medications

These symptoms do not occur in everyone, and their severity can vary substantially between patients. Changing the dose, hormone formulation, or delivery method can sometimes improve treatment tolerability.

It is also important to remember that the term HRT covers several very different medications. An estradiol patch, oral progesterone, testosterone injection, and hormone pellet do not have identical side-effect profiles.

Our guide to the different types of HRT, including pills, patches, gels, injections, and pellets explains these differences in greater detail.

What Side Effects Can Estrogen Cause?

Estrogen therapy is commonly used for women experiencing menopausal symptoms such as hot flashes, night sweats, sleep disruption, and vaginal symptoms.

Potential estrogen-related side effects may include:

• Breast tenderness

• Bloating

• Fluid retention

• Headache

• Nausea

• Changes in mood

• Vaginal spotting or bleeding

• Skin irritation when using a patch or topical medication

Some women notice temporary changes in weight related to fluid retention or bloating. This should be distinguished from long-term changes in body fat or body composition.

Transdermal estrogen, such as a patch or gel, may also cause redness, itching, or irritation where the medication is applied.

If you are considering estrogen therapy specifically, our physician guide to HRT for women during menopause and beyond provides a more detailed overview.

What Side Effects Can Progesterone Cause?

Women who still have a uterus and use systemic estrogen generally need appropriate progesterone or another progestogen to help protect the lining of the uterus.

Depending on the medication and individual response, progesterone may cause:

• Fatigue or drowsiness

• Breast tenderness

• Headache

• Mood changes or irritability

• Abdominal discomfort

• Fluid retention

• Changes in vaginal bleeding

Some people tolerate one progesterone or progestogen formulation better than another. Medication timing can also matter because certain forms of progesterone may cause sleepiness.

One particularly important issue is using systemic estrogen without adequate endometrial protection in a woman who still has a uterus. Unopposed systemic estrogen can stimulate the uterine lining and increase the risk of endometrial hyperplasia and endometrial cancer. The FDA continues to maintain specific warning language regarding this risk.

What Are the Side Effects of Testosterone Replacement Therapy?

Testosterone replacement therapy has a different side-effect profile from menopausal estrogen and progesterone therapy.

Potential testosterone-related side effects may include:

• Acne or oily skin

• Increased body or facial hair

• Fluid retention

• Changes in libido

• Injection-site discomfort

• Skin irritation from topical testosterone

• Increased red blood cell production

• Reduced sperm production and fertility

One of the most important laboratory findings to monitor during testosterone therapy is hematocrit, because testosterone can increase red blood cell production. The American Urological Association identifies elevated hemoglobin and hematocrit as the most frequent adverse event associated with testosterone therapy.

That is one reason periodic blood testing is commonly incorporated into testosterone treatment.

You can learn more in our guide to testosterone replacement therapy (TRT) for men.

Can Testosterone Replacement Therapy Affect Fertility?

Yes.

External testosterone can suppress the hormonal signals from the brain that normally tell the testicles to produce testosterone and sperm.

As a result, testosterone replacement therapy can:

• Lower sperm counts

• Suppress sperm production

• Reduce fertility

• Cause testicular shrinkage in some men

Men who are planning to have children should discuss their fertility goals with their physician before beginning testosterone therapy. The Endocrine Society recommends against starting testosterone therapy in men who are planning fertility in the near future.

Do HRT Side Effects Depend on How the Hormone Is Taken?

Yes. The route of administration can significantly affect both side effects and risk.

For example, oral estrogen passes through the liver before reaching the systemic circulation, while transdermal estrogen delivered through a patch or gel largely avoids this initial liver metabolism.

This difference can influence blood-clotting and metabolic effects. The Menopause Society notes that blood-clot risk is increased with oral hormone therapy and may be lower with transdermal estrogen.

Other route-specific considerations include:

Patches:
May cause local redness, itching, or adhesive irritation.

Gels and creams:
May irritate the skin. Testosterone gels also require precautions to prevent accidental transfer of medication to another person.

Injections:
May cause temporary pain, bruising, or irritation at the injection site. Depending on the formulation and dosing interval, hormone levels may also fluctuate between injections.

Pellets:
Potential procedure-related side effects include bruising, discomfort, bleeding, infection, pellet extrusion, and scarring. Because pellets remain implanted for an extended period, the dose cannot be adjusted as quickly if side effects occur.

This is why the "best" form of hormone therapy differs from patient to patient.

Are There Serious Risks Associated With Menopausal Hormone Therapy?

There can be, although the risk is highly individualized.

Potential clinically important risks associated with systemic menopausal hormone therapy may include:

• Blood clots

• Stroke

• Gallbladder disease

• Breast cancer with certain hormone regimens and durations of treatment

• Endometrial hyperplasia or cancer when systemic estrogen is used without adequate uterine protection

The magnitude of these risks is not the same for every woman.

Age, how close someone is to menopause, personal and family medical history, smoking, cardiovascular health, history of blood clots, the hormone being prescribed, dose, route of administration, and duration of therapy can all influence the overall benefit-risk balance.

For many otherwise healthy women who begin menopausal hormone therapy before age 60 or within approximately 10 years of menopause onset, professional menopause guidance considers the overall benefit-risk profile favorable when there is an appropriate indication for treatment.

For a more detailed discussion, see The Benefits and Risks of HRT: What Current Research Shows.

Didn't the FDA Change Its HRT Warnings?

Yes.

In February 2026, the FDA approved labeling changes for menopausal hormone therapy products that removed boxed-warning statements concerning cardiovascular disease, breast cancer, and probable dementia.

The FDA retained the boxed warning regarding endometrial cancer from systemic estrogen-alone therapy in women with a uterus.

This change does not mean that hormone therapy has no risks.

Instead, it reflects the importance of interpreting hormone therapy evidence in context rather than assuming that every woman using every type of hormone therapy has the same risk.

Modern hormone treatment should therefore involve individualized risk assessment rather than either assuming HRT is universally dangerous or universally beneficial.

When Should You Contact Your Physician About HRT Side Effects?

Contact your physician if you develop persistent or concerning symptoms after starting or changing hormone therapy, including:

• Persistent headaches

• Significant mood changes

• Excessive acne

• Significant swelling or fluid retention

• Persistent breast tenderness

• Unexpected vaginal bleeding

• Heavy or prolonged bleeding

• Significant injection-site reactions

• New problems that began after starting treatment

Unexpected vaginal bleeding deserves particular attention, especially in a woman who has already completed menopause.

Your physician may recommend modifying the dose, changing the route of administration, ordering additional testing, or evaluating another possible cause of the symptom.

When Should You Seek Immediate Medical Attention?

Certain symptoms require urgent medical evaluation because they may indicate a serious medical problem.

Seek immediate medical attention for symptoms such as:

• Sudden chest pain

• Sudden shortness of breath

• Coughing up blood

• New significant swelling or pain in one leg

• Sudden weakness or numbness

• Facial drooping

• Difficulty speaking

• Sudden significant vision changes

• A severe new neurologic symptom

• Severe allergic reaction or difficulty breathing

These symptoms should not simply be assumed to be a normal side effect of hormone therapy.

Can HRT Side Effects Be Reduced?

Often, yes.

Experiencing a side effect does not necessarily mean that hormone therapy must be permanently discontinued.

Depending on the situation, your physician may consider:

• Lowering the dose

• Changing the timing of the medication

• Switching from an oral medication to a transdermal option

• Changing the hormone formulation

• Adjusting the injection dose or frequency

• Reassessing whether every prescribed hormone is necessary

• Evaluating another medical condition that may be causing the symptom

The goal of hormone therapy is not to achieve the highest possible hormone level.

The goal is to use an appropriate treatment to improve clinically meaningful symptoms while minimizing unnecessary exposure and potential adverse effects.

Why Is Monitoring Important During Hormone Replacement Therapy?

Hormone therapy should be periodically reassessed rather than prescribed indefinitely without follow-up.

Monitoring may include a combination of:

• Symptom review

• Side-effect review

• Blood pressure

• Medication response

• Changes in medical or family history

• Appropriate preventive screening

• Laboratory testing when clinically indicated

For testosterone therapy, monitoring commonly includes testosterone levels and a complete blood count or hematocrit, along with other testing based on age, medical history, prostate considerations, and treatment goals. The Endocrine Society recommends evaluating men after testosterone therapy begins to assess treatment response and adverse effects.

For menopausal hormone therapy, treatment decisions are often guided by symptoms, age, medical history, risk factors, medication type, and clinical response rather than simply trying to reach a particular hormone number.

Read more about how laboratory testing may help personalize HRT and what to expect in our Patient's Guide to Starting Hormone Replacement Therapy.

Is Hormone Replacement Therapy Safe?

HRT can be appropriate and well tolerated for many patients, but there is no single answer that applies to everyone.

Safety depends on:

• Which hormone is being prescribed

• Why treatment is being used

• Your age

• Your medical history

• Your personal and family history

• Your cardiovascular and blood-clot risk

• Whether you have a uterus

• Your fertility goals

• The dose

• The route of administration

• How long treatment is used

• How you respond to treatment

• Whether appropriate follow-up is performed

This is why hormone therapy should be prescribed as an individualized medical treatment rather than according to a one-size-fits-all protocol.

If you are trying to decide whether treatment may be appropriate, read Is HRT Right for You? A Physician's Guide to Individualized Care.

The Bottom Line

Hormone replacement therapy can cause side effects, but the type and likelihood of those side effects depend heavily on the individual treatment.

Estrogen and progesterone may cause breast tenderness, bloating, headaches, mood changes, or changes in bleeding. Testosterone can cause acne, increased red blood cell production, fluid retention, and suppression of fertility. Patches, topical medications, injections, and pellets also have their own route-specific considerations.

Serious complications are possible but should be evaluated in the context of the individual patient's age, medical history, treatment type, route, dose, and overall health.

The safest approach is not simply to ask whether HRT is "safe" or "unsafe." It is to determine whether a specific hormone treatment is appropriate for a specific patient and then monitor that treatment appropriately over time.

For additional education, explore our Hormone Replacement Therapy Resource Center.

If you are considering treatment, you can also learn more about Hormone Replacement Therapy at Ask Dr. Hu, including individualized evaluation and treatment options for women and men throughout Arizona.

Evidence-Based Medical References

This article is intended to provide evidence-informed patient education. Hormone therapy recommendations should be individualized according to the treatment being considered, medical history, symptoms, risk factors, reproductive goals, and ongoing clinical response.

Authoritative sources used in developing and reviewing this information include:

• The U.S. Food and Drug Administration, including its current information and 2026 labeling updates for menopausal hormone replacement therapy.

• The Menopause Society, which provides clinical and patient guidance regarding the benefits, risks, timing, and routes of menopausal hormone therapy.

• The Endocrine Society Clinical Practice Guideline on Testosterone Therapy in Men With Hypogonadism, which addresses diagnosis, patient selection, fertility considerations, and treatment monitoring.

• The American Urological Association Testosterone Deficiency Guideline, including recommendations regarding testosterone treatment and hematocrit monitoring.

• MedlinePlus, a service of the U.S. National Library of Medicine, for patient information about menopausal hormone therapy and medication side effects.

Medical evidence, medication labeling, and clinical recommendations can change over time. Individual treatment decisions should be made with a qualified healthcare professional familiar with the patient's complete medical history.

About the Author

YiQiu Hu, NMD

Dr. YiQiu Hu is an Arizona-licensed naturopathic physician and founder of Ask Dr. Hu. His clinical work focuses on concierge medicine, preventive healthcare, health optimization, laboratory evaluation, medical weight management, hormone care, integrative pain management, and individualized treatment planning.

At Ask Dr. Hu, Dr. Hu provides personalized medical care for patients throughout Arizona with an emphasis on thorough evaluation, clear patient education, evidence-informed treatment options, and ongoing physician-patient relationships.

This article is provided for general educational purposes and does not replace individualized medical evaluation, diagnosis, or treatment.