Progesterone Side Effects: What's Normal, What's Not

When you’re dealing with the hormonal seesaw of perimenopause or stop-and-start irregular periods, you may have started—or are considering—hormone therapy. For many women, progesterone is prescribed as part of HRT. And often at the top of the list of women’s concerns? The side effects of progesterone. 

Here’s some good news: Progesterone side effects are usually mild and often settle within a few weeks.

Different types of progestogens (which are steroid hormones that bind progesterone receptors in the body) exist, including micronized progesterone (which is chemically identical to the progesterone your body makes) and synthetic progestins (which have a different chemical structure). Each can affect women differently, so it’s important to know which one you’re taking.

Below, we’ll go over what progesterone does in the body, common side effects—including which ones need particular attention—and progesterone intolerance. And we’ll tell you how an experienced clinician (like one at Midi) can guide you through the process and help you make any needed adjustments.

What Progesterone Does and Why It’s Prescribed

Wondering what progesterone does for women and why you might need it? All of your life, it’s played an essential role in your menstrual cycle—helping regulate your cycle’s timing and limiting estrogen’s impact on your uterus, among other things. 

In perimenopause, progesterone production begins to decline, so some women are prescribed it as part of HRT. Clinicians typically prescribe progesterone alongside estrogen in women who have a uterus. That’s because estrogen causes the uterine lining to thicken, and progesterone protects that lining from overgrowth. Depending on the type, it can also help manage heavy or irregular perimenopausal bleeding or support sleep.

Women who have had a hysterectomy generally don’t need progesterone because they no longer need uterine protection, so they may be able to take estrogen alone.

Progesterone can be taken orally or, in special cases of progesterone intolerance, vaginally under care of a clinician. Progestins can also be delivered through an IUD. The right option depends on why you need progesterone and how well you tolerate it. 

Finally, keep in mind that topical progesterone is not used due to unreliable absorption, making it ineffective at providing endometrial (uterine) protection.

Micronized Progesterone vs. Synthetic Progestins

When it comes to the types of progesterone, here’s a simple breakdown: 

• Micronized progesterone: Micronized progesterone is chemically identical, or bioidentical, to the progesterone your body produces. (You might have heard it called by its popular brand name, Prometrium.) Research suggests that micronized progesterone may be associated with a lower breast cancer risk than synthetic progestins when each is used with estrogen. 
• Synthetic progestins: These hormones are made in the lab. They mimic the body’s natural progesterone. Sometimes they’re prescribed because they can better suppress the uterine lining and may help control heavy bleeding. 

The differences between micronized progesterone and synthetic progestins can affect how women experience side effects, including mood changes. The differences may also factor into breast and cardiovascular health, which is one reason why a conversation about your health history with your clinician is so important.

The Most Common Progesterone Side Effects

One thing you may wonder: “Does progesterone make you tired?” Yes, some women experience drowsiness, especially from micronized progesterone. For many, sleepiness can be a potential benefit, especially for those experiencing sleep disruption. This is why clinicians usually recommend taking it at night.

Other possible side effects include: 

• dizziness and lightheadedness 
• breast tenderness and swelling 
• bloating, fluid retention, and abdominal cramping 
• headache 
• light spotting

Many of these side effects are most felt in the first few weeks of taking progesterone pills, then they taper off. But if any side effects feel debilitating or are getting in the way of your daily life, let your clinician know.

Mood Changes on Progesterone: Better for Some, Worse for Others

Progesterone can have different effects on mood—some women find it has a calming effect and improves sleep (especially micronized progesterone), whereas others may feel anxious, irritable, or sad.

One hypothesis involves allopregnanolone, a substance the body makes from progesterone. It affects receptors in the brain involved in mood and relaxation. Some women may be more sensitive to changes in allopregnanolone than others. Those who have a history of premenstrual mood sensitivity or premenstrual dysphoric disorder (PMDD), a severe form of PMS, may have a greater sensitivity to hormonal changes. 

If you feel like your mood has gotten worse while taking progesterone, it’s a reason to contact your clinician. Don’t push through on your own or assume that it’s normal to feel this way.

Does Progesterone Cause Weight Gain?

When starting hormone therapy, you may wonder how progesterone will impact your weight. But research shows that taking micronized progesterone as part of HRT doesn’t cause an increase in body weight or BMI. The temporary fluid retention and bloating that some women experience may feel like extra pounds, but it actually isn’t.

But midlife weight gain does happen—most likely due to several contributing factors, including aging, menopause-related hormonal changes, and lifestyle factors like different eating habits or getting less exercise. Some women report a change in appetite when taking progesterone, but that doesn’t happen to everyone.

As your body adjusts to the medication over the first several weeks, you may feel less bloated. But if it persists or is particularly bothersome, bring it up with your clinician. And if you’re gaining or losing weight without an obvious explanation, it’s worth looking into other possible causes, instead of assuming it’s from progesterone.

Side Effects That Warrant Contacting Your Clinician

Some uncommon side effects that warrant immediate medical attention when taking progesterone: 

• signs of a blood clot, including leg swelling or calf pain 
• chest pain 
• sudden shortness of breath 
• sudden severe headache 
• vision changes or difficulty speaking 

A few other important points:

• An allergic reaction to progesterone is uncommon, but signs such as rash or swelling should be evaluated. And get emergency care if you have difficulty breathing or swelling of the face, mouth, tongue, or throat. 
• If you have unexpected vaginal bleeding, particularly after menopause, always tell your clinician.
• New or worsening depression is also a reason to contact your clinician (but get emergency care for any thoughts of self-harm).

Overall, these are uncommon side effects—consider them warning signs that you should be aware of, not reactions you should expect while taking progesterone. 

Progesterone Intolerance: When You Genuinely Feel Worse

A small percentage of women may have an intolerance to progesterone. 

This may produce symptoms such as significant mood changes or excessive fatigue, bloating, or breast tenderness. Women with a history of significant premenstrual mood symptoms may be particularly sensitive to hormonal changes. Progesterone intolerance is different from a true allergic reaction.

Even if you have progesterone intolerance, hormone therapy isn’t necessarily off the table. Your clinician has several options, including lowering the dose or switching the delivery method (from pills to vaginal progesterone, for example). Switching to a cyclic schedule or trying a levonorgestrel IUD for endometrial protection may also be options.

Don’t stop progesterone on your own; have an open conversation with your clinician, who may be able to find an adjustment that works for you. 

How to Reduce Progesterone Side Effects

The best way to deal with progesterone side effects depends on which ones you’re experiencing.

Midi clinicians generally recommend taking micronized progesterone at bedtime to deal with the sleepiness side effect—and in fact, if you’ve been having trouble sleeping, this side effect can actually be a real benefit.

For mild bloating or cramps, a ginger supplement may help. (Ask your clinician whether it’s right for you, and if so, what dosage to start with.)

You can also ask your healthcare professional about a schedule switch. Progesterone can be prescribed as a daily dose or via cyclic dosing, in which you take progesterone for a set number of days each month rather than every day. If you’re having trouble with side effects from a daily dose, ask your clinician whether a different dosing schedule might work for you.

It can take time for your body to adjust to progesterone. Common side effects often improve within the first 2 to 4 weeks, so give it a chance and speak with your clinician before deciding that it’s not working for you. 

Who Should Be Cautious With Progesterone

Women with a history of clotting disorders, liver disease, or certain cancers should have a careful conversation with their clinician before deciding to take progesterone. Also alert your clinician if you have a peanut allergy: Some oral progesterone formulations contain peanut oil and may be dangerous for you.

Certain medications can also interact with progesterone, potentially affecting how either of the drugs are metabolized in the body. This is another reason to make sure your clinician knows about any prescription medications, over-the-counter drugs, and supplements you take.

Your clinician can help weigh the potential risks and benefits of taking progesterone, based on your individual health history, and help you deal with any side effects that pop up. That’s why it’s so important to get a personal assessment from a menopause-trained clinician, like one at Midi, so you can make the best decisions for your health. 

Key Takeaways

• Common progesterone side effects include drowsiness, dizziness, breast tenderness, bloating, headache, and mood changes. Many mild side effects improve as your body adjusts.
• Taking micronized progesterone at bedtime can help minimize daytime drowsiness, and its sedating effect may help with sleep.
• Some women are more sensitive to progesterone than others. If side effects are difficult to tolerate, your clinician may be able to adjust your dose or dosing schedule, or prescribe a different type (such as vaginal progesterone).
• While most progesterone side effects are mild, uncommon symptoms such as chest pain, sudden shortness of breath, signs of a blood clot, or thoughts of self-harm require immediate medical attention.
• Progesterone isn’t a one-size-fits-all solution. Your health history, symptoms, other medications, and response to treatment can all help your clinician figure out the safest and most tolerable approach for you.

Frequently Asked Questions (FAQs)

What is the most common problem with progesterone?

Drowsiness or dizziness are common side effects of oral progesterone, along with breast tenderness, bloating, headache, and mood changes. These effects are often most noticeable when you first start taking progesterone and generally ease as your body adjusts. Taking micronized progesterone at bedtime can help minimize daytime drowsiness.

What should you avoid while taking progesterone?

When you first start taking progesterone, see whether you’re affected by drowsiness or dizziness before you drive a car. Tell your clinician about all prescription medications, over-the-counter drugs, and supplements you take, since some may interact with progesterone. Ask your clinician whether you should avoid or limit things that also have a sedating effect, like sleep aids.

What happens when you start taking progesterone pills?

When you start taking progesterone pills, you may notice side effects like dizziness, drowsiness, breast tenderness, bloating, headache, or mood changes. Many common side effects improve as your body gets used to the medication, but let your clinician know if they are severe, persistent, or getting in the way of going about your daily life.

Can progesterone help with anxiety?

Its effect on mood varies: Progesterone can have a calming effect for some women, but others may experience anxiety, irritability, or low mood while taking it. If you notice new or worsening anxiety or other mood changes after starting progesterone, talk with your clinician rather than assuming you need to push through it.

What are the signs of low progesterone?

Low progesterone is often a result of not ovulating (anovulation), which is common in perimenopause and can show up alongside signs like irregular periods or unpredictable bleeding.