Roughly 85% of women experience hot flashes or sleep disturbances during hormonal transitions, yet many are unsure which therapy option is right for them. One of the most common questions asked is whether progesterone is needed when taking estrogen for menopause symptoms.(1)
The short answer: If a woman still has her uterus, progesterone is generally necessary to protect it. But why?(2)
The answer lies in how estrogen and progesterone interact with the endometrium, or uterine lining. While estrogen is highly effective at relieving menopause-related symptoms, it also stimulates the growth of the uterine lining. Without progesterone to counter this effect, the growth can become excessive and lead to serious complications.(3)
This article covers how each hormone works, the benefits and risks of combined hormone replacement therapy, and practical considerations for starting treatment. While risks do exist, they’re not guaranteed and can often be managed with personalized care from a menopause-trained provider.
Understanding Estrogen's Role in the Body
Estrogen is a group of hormones that includes estradiol, estrone, and estriol. Estradiol is the most potent form and is typically used in hormone replacement therapy (HRT).(4)
Estrogen's main functions include the following:
Supporting the development of breasts and reproductive organs
Regulating the menstrual cycle by thickening the endometrium
Maintaining bone density
Supporting cardiovascular and brain health
Enhancing skin elasticity and hydration
When estrogen levels decline during menopause, these functions can be disrupted, leading to unwanted symptoms and an increased risk of osteoporosis.
Understanding Progesterone: The Balancing Hormone
Progesterone is a hormone primarily produced by the ovaries after ovulation. It plays a vital role in reproductive health and hormone balance.(5)
The key functions of progesterone are the following:
Preparing the endometrium for implantation during the menstrual cycle
Maintaining the early stages of pregnancy
Countering estrogen's effects on the endometrium by limiting the thickening of the endometrial lining
Helping with sleep and mood regulation
Sources of progesterone include the ovaries (after ovulation), the adrenals, and the placenta during pregnancy. In HRT, it's important to distinguish between natural progesterone (used by Winona) and synthetic progestins, which can behave differently in the body and may carry different risk profiles.(5)
Estrogen vs. Progesterone: How do they compare and interact?
Category | Estrogen | Progesterone |
Primary Function | Develops and maintains female reproductive tissues and secondary sex characteristics | Prepares the uterus for implantation and maintains early pregnancy |
Produced by | Ovaries (mainly), adrenal glands, and fat tissue | Corpus luteum (in ovaries), placenta during pregnancy, and adrenal glands |
Phases of the Menstrual Cycle | Peaks during the follicular phase (first part of the menstrual cycle) | Peaks during the luteal phase (second half of the menstrual cycle) |
Effects on the Uterus | Stimulates endometrial thickening | Stabilizes the endometrium for implantation |
Effects on Cervical Mucus | Thins mucus, making it more receptive to sperm | Thickens mucus, making it less penetrable |
During Perimenopause | Levels fluctuate irregularly, which may lead to noticeable symptoms | Levels often decline more sharply, leading to unopposed estrogen effects |
Postmenopause | Levels decline gradually | Drops significantly; deficiency may increase sensitivity to estrogen effects |
HRT (Hormone Replacement Therapy) | Often used in both estrogen-only and combined formulations | Used in combination with estrogen to protect the uterus from endometrial hyperplasia |
Cancer Risk Considerations | Unopposed estrogen increases the risk of endometrial cancer | Has a protective effect against endometrial cancer when combined with estrogen |
Common Forms in HRT | Estradiol (oral, transdermal, vaginal) | Micronized progesterone (oral, transdermal) and synthetic progestins (oral, vaginal) |
Interaction Summary | Stimulates tissue growth and reproductive readiness | Balances estrogen's effects, stabilizes tissues, and supports implantation |
Together, estrogen and progesterone work in rhythm throughout the reproductive cycle and can be used in combination during menopause to mimic this natural balance.(2)(4)(5)(6)
The Crucial Question: Do women need progesterone with estrogen?
For most people who have not had a hysterectomy, the answer is yes. Progesterone is not just a tag-along; it has a crucial role in making estrogen therapy safe for the uterus.(2)
Why? The Uterine Factor
Estrogen-only HRT (unopposed estrogen) stimulates the endometrium to grow. Over time, this can lead to endometrial hyperplasia, a thickening of the lining that may progress to endometrial cancer if left unaddressed.(3)(4)(6)
Progesterone's Protective Role
Progesterone counters this effect by transforming the endometrium into a stable state, reducing the risk of abnormal growth. Depending on the treatment approach, progesterone either promotes regular shedding of the lining (cyclic therapy) or keeps it consistently thin (continuous therapy). This uterine protection is the primary reason progesterone is recommended when estrogen is prescribed to individuals with an intact uterus.(2)(3)(4)(6)(7)
Exception: Women Without a Uterus
For women who have had a hysterectomy, estrogen-only therapy is often appropriate. There’s no endometrial lining to protect.(2)
However, emerging research suggests that progesterone may have additional benefits beyond just uterine protection, such as effects on mood or sleep, but these uses are still under investigation and are not yet standard.(4) Typically, treatment is individualized, and a menopause specialist can discuss whether progesterone should be considered for a patient post-hysterectomy.
What are the benefits of taking combined HRT?
Symptom Relief
Estrogen is the primary hormone needed for relieving menopause symptoms and is supported by progesterone. Combined HRT is effective for treating the following symptoms:
Hot flashes and night sweats
Vaginal dryness, irritation, and painful intercourse
Sleep difficulties and mood fluctuations
Brain fog
Joint pain and body discomfort
Bone Health
Hormones support bone strength and help reduce the risk of osteoporosis and fractures. Estrogen slows bone loss by preserving bone mineral density, while progesterone can stimulate bone-building activity by supporting osteoblast function (cells that produce the materials needed for strong bone tissue)(4)
Other Potential Benefits
Combined HRT has been shown to have the following benefits:
These effects vary by individual and should not be the sole reason to start HRT.
What are the risks and side effects of taking progesterone with estrogen therapy?
Common Side Effects
Some individuals may experience side effects when starting HRT, particularly in the early weeks of treatment. These effects are generally mild and temporary. As the body adjusts to the new hormone levels, most symptoms improve or resolve entirely.
Estrogen and progesterone therapy may cause these common side effects:(7)
Nausea
Breast tenderness
Headaches
Fluid retention
Bloating
Mood shifts or irritability
Drowsiness
Irregular vaginal bleeding or spotting (especially early on)
Irregular bleeding is often temporary and linked to endometrial adjustment. In most cases, it resolves with continued HRT use or dose modification.
A board-certified physician trained in menopause care can offer guidance on managing symptoms or adjusting the treatment plan, if needed.
Potential Risks
Like all medications, combined HRT comes with a few potential risks:(1)(4)(7)
Blood clots or venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism
Stroke, with a higher risk in older women or those with preexisting risk factors
Slightly increased risk of breast cancer, especially with synthetic progestins
Heart disease
Gallbladder disease
Risks are low in healthy individuals who start HRT before age 60 (or within 10 years of menopause onset). Fortunately, these risks are not certain, and some, like blood clots, can be avoided with certain lifestyle adjustments. It’s important to be aware of the potential risks, highlighting why decision-making and treatment around HRT should be tailored to individual health needs.
Taking Estrogen Without Progesterone
Those with a uterus who take systemic estrogen without progesterone increase their risk of developing any of the following:(6)(9)(10)
Simple endometrial hyperplasia without atypia (mild uterine lining overgrowth, normal cells)
Complex endometrial hyperplasia without atypia (crowded uterine lining overgrowth, normal cells)
Atypical hyperplasia (abnormal uterine lining cells, carries a higher risk of becoming cancerous)
This is why unopposed estrogen is not recommended unless the patient has had a hysterectomy.
Unlike systemic estrogen, vaginal estrogen is safe for all women to use, no matter if they still have their uterus or not. Vaginal estrogen cream is locally absorbed and helps to restore healthy tissue and a healthy microbiome of the vagina, and it reduces many symptoms of the genitourinary syndrome
Practical Aspects of Taking Combined HRT
Forms of Administration
Oral Tablets or Capsules: These are available as separate or combined forms of micronized estrogen and progesterone, including estrogen tablets and capsules containing progesterone.
Transdermal Patches: These patches deliver estrogen through the skin, which can help reduce clotting risk. The patch is typically prescribed along with a progesterone capsule.
Topical Creams: These creams deliver estrogen and progesterone through the skin, bypassing the liver and often allowing lower doses. Options include separate creams or a combined estrogen-progesterone formula.
Best Time of Day to Take Estrogen and Progesterone
Estrogen
This is usually taken at the same time daily. Morning or evening are both fine.
Progesterone
It’s often recommended at night due to its calming effect.
It’s crucial to follow individualized guidance from a provider.
What to Expect When Starting Combined HRT
When beginning combination estrogen-progesterone therapy, it's important to keep in mind the following:
It's not uncommon for some side effects to occur as the body adjusts.
Hot flashes and sleep problems can improve within a few weeks.
Full benefits often appear within two to three months.
Regular follow-ups with a menopause specialist are vital to evaluate individual response, adjust dosing, and ensure long-term safety.
Essential Progesterone
For women with a uterus, taking estrogen with progesterone is not optional; it’s essential for safety. Progesterone protects the uterine lining from overgrowth and reduces the risk of cancer. Beyond protection, the combination can also support sleep, stabilize mood, and improve menopausal symptom relief.
HRT should always be tailored to individual health history, symptom profile, and goals. For the safest and most effective treatment, consult with a menopause-informed provider who understands the full scope of HRT options and how to personalize care.
Estrogen and progesterone work best when used together thoughtfully, and when it comes to menopause care, balance isn’t key.
Experiencing symptoms of hormonal imbalance? Learn more about HRT.
Over 35 and struggling with hormone-related symptoms? There’s no need to struggle in silence. Take this brief quiz to see if you’re an eligible candidate for HRT. Get started with Winona to take the first step toward feeling better.
