Progesterone is part of hormone replacement therapy (HRT) for people who have been through menopause and still have a uterus. Possible side effects include spotting, headaches, and breast tenderness.

Doctors typically prescribe progesterone in combination with estrogen. This is called combined hormone replacement therapy (HRT).

In combined HRT, estrogen replacement helps treat menopause symptoms while progesterone replacement helps reduce some of the risks of taking estrogen.

This article provides information about progesterone and combined HRT.

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During menopause, the ovaries produce much lower levels of the hormones estrogen and progesterone than they did previously. This can result in widespread menopause symptoms such as:

HRT uses synthetic forms of estrogen and progesterone to replenish levels of these hormones in the body.

According to the United Kingdom’s National Health Service (NHS), there are two types of HRT. Estrogen-only HRT involves only estrogen, and combined HRT involves both estrogen and progesterone.

Estrogen can relieve menopause symptoms and reduce the risk of certain diseases. However, it can also cause abnormal thickening of the lining of the uterus, which increases the risk of uterine cancer.

Progesterone helps prevent thickening of the uterine lining, thereby decreasing the risk of uterine cancer. For this reason, doctors may prescribe combined HRT to people who are in postmenopause and still have a uterus.

According to the label for Prometrium, a progesterone pill, common and less serious side effects of the medication include:

Side effects that are less common and more serious include:

  • sudden new, severe headaches
  • changes in vision or speech
  • dizziness
  • severe chest and leg pain
  • vomiting

A person should contact a healthcare professional as soon as possible if they experience any of these side effects.

Common side effects of combined HRT are similar to those of the Prometrium pill. They include:

According to the NHS, serious side effects from continuous combined HRT are rare but may include:

  • pain, swelling, or redness in one leg, which may indicate deep vein thrombosis (DVT)
  • one or more of the following changes in the breasts, which could indicate breast cancer:
    • a lump
    • dimpled skin
    • changes in the nipple
  • changes in vaginal bleeding after taking HRT for several months, which could indicate uterine cancer

Additionally, combined HRT may increase a person’s risk of breast cancer compared with estrogen-only HRT.

Tips for coping with combined HRT side effects include:

  • taking pain relievers to alleviate headaches
  • taking HRT medications with food to help reduce nausea
  • performing gentle stretches and exercises to help prevent muscle cramps
  • drinking plenty of fluids to prevent dehydration during episodes of diarrhea

Anyone who experiences side effects while taking HRT should make an appointment with a doctor to discuss their options.

Doctors may recommend adjusting the dosage or switching to a different HRT medication.

One possible complication of taking the Prometrium progesterone pill is abnormal blood clotting, which can cause a stroke, a heart attack, a pulmonary embolism, or vision problems.

Taking a progesterone pill can also cause developmental irregularities in any fetus that may be present if a person is still able to become pregnant while they are taking HRT. Using a barrier method, such as condoms, during sex can reduce this risk.

Combined HRT may also increase a person’s risk of breast cancer compared with estrogen-only HRT.

Doctors will not prescribe Prometrium to anyone who:

  • is experiencing abnormal vaginal bleeding without a known cause
  • has a suspected or known history of breast cancer
  • has DVT or a pulmonary embolism or has had either in the past
  • has a history of stroke or heart attack
  • has liver problems
  • is pregnant or may be pregnant

A doctor will assess all risks before prescribing the medication. A person should report any concerning side effects or symptoms to a medical professional immediately.

A person should contact a doctor if HRT does not help relieve their menopause symptoms or if they experience any of the following:

  • headaches that are severe or last longer than 1 week
  • nausea or sickness that lasts longer than 1 week
  • diarrhea that lasts longer than 1 week
  • muscle cramps that persist for more than a few months after starting HRT
  • mood changes that persist for more than a few months after starting HRT

People with one or more of the following symptoms should see a doctor as soon as possible:

  • breast pain or tenderness lasting more than 6 weeks
  • changes to the breast or nipple
  • heavy or unexpected vaginal bleeding 6 months or more after starting HRT

Below are some answers to frequently asked questions about progesterone HRT.

What are the benefits of progesterone HRT?

Doctors typically prescribe progesterone alongside estrogen as part of combined HRT.

Taking estrogen alone thickens the lining of the uterus and can increase the risk of uterine cancer.

Taking progesterone alongside estrogen helps prevent thickening of the uterine lining, thereby helping to protect against uterine cancer.

Which progesterone HRT has the least side effects?

According to the UK-based organization The Menopause Charity, micronized progesterone typically causes fewer side effects than other types of progestogen.

This type of progesterone is “body identical,” which means it has the same molecular structure as the progesterone that the body produces naturally.

People who are going through menopause may take synthetic progesterone as part of hormone replacement therapy (HRT).

Doctors typically prescribe combined HRT, which involves taking progesterone alongside estrogen. The addition of progesterone helps thin the lining of the uterus, thereby reducing the risk of uterine cancer.

Combined HRT can cause side effects such as headaches, nausea, and breast pain or tenderness. These side effects usually resolve with time, but a person should consult a doctor if symptoms persist. A doctor may recommend adjusting the dosage or switching to a different type of HRT.

People should contact a doctor as soon as possible if they experience particularly concerning symptoms such as changes to their breasts or nipples or heavy or unexplained vaginal bleeding 6 months or more after starting HRT.

These symptoms could indicate a more serious issue that requires further investigation and treatment.