What is Chiari-Frommel Syndrome (CFS)?

Chiari-Frommel syndrome (CFS) is a rare genetic disorder that affects women who have recently given birth (postpartum).^1,2 Also known as lactation‐uterus atrophy, postpartum galactorrhoea‐amenorrhea syndrome, it is characterised by the absence of regular menstrual periods (amenorrhea) and ovulation (anovulatory), and an abnormal production of breast milk (galactorrhoea).^1,2

Before pregnancy, these symptoms are considered to be normal, and these initial symptoms are not seen as a reason for concern; however, if these symptoms continue for longer than 6 months after birth, it is considered CFS.^1,2

What are the symptoms of CFS?

CFS usually affects young women between the ages of 17 and 35, and the majority of them are underweight or poorly nourished.^1,2 They often seek medical help because of persistent breast milk production (even though they’re not breastfeeding), as well as low energy, headaches, and abdominal discomfort.^1,2 Other symptoms include feeling emotionally drained or depressed, especially if treatments have been unsuccessful in preventing milk flow or bringing back their periods.^1,2

Doctors often notice enlarged breasts with ongoing milk discharge, and a smaller-than-normal uterus and cervix.^1,2 The vaginal area is typically dry, and uterine shrinkage (atrophy) is a common occurrence.^1,2 Many women also experience weight gain and increased tiredness over time.^1,2

Other signs include thinning of the uterine lining, low oestrogen levels (which cause the vaginal tissues to become thin and dry), and low levels of FSH, a hormone important for ovulation. ^1,2

What causes CFS?

The exact cause of CFS is unknown, but there is a link to hyperprolactinemia (HP), which is abnormally high levels of the hormone prolactin (a stimulator of lactation) in the blood, due to abnormal hypothalamic and/or pituitary gland activity.^1,2 The causes of an abnormal hypothalamus and/or pituitary gland have been linked to very small tumours found in them, caused by hormones associated with pregnancy, i.e. prolactin.^1,2,4

There is also a theory that oral contraceptives, such as birth control, may play a role in causing this; however, there is no research that proves this theory as of yet.¹

Treatments for CFS

Dopamine agonists

In our bodies, dopamine is a natural brain chemical that helps control the release of the hormone prolactin.³ Under normal conditions, dopamine helps regulate prolactin levels.³ When prolactin levels are too high in conditions like Chiari-Frommel Syndrome, medications called dopamine agonists can be prescribed by a health professional to help restore balance.^3,5

How do dopamine agonists work?

Dopamine agonists act like dopamine in the body by attaching to receptors on the cells that produce prolactin.³ This sends a signal to the cell to slow down or stop producing prolactin.³ By doing this:³

• Prolactin levels in the blood go down
• Menstrual cycles and ovulation return to normal
• If there's a prolactin-secreting tumour (a prolactinoma), dopamine agonists can shrink it in size

The dopamine agonists work by quickly reducing how much prolactin the cells release, slowing the cells’ ability to make prolactin long-term and sometimes even causing the cells to shrink or die off naturally, decreasing prolactin release.³

Which dopamine agonists are commonly used?

There are several effective dopamine agonists:³

• Bromocriptine (widely used and well-studied)
• Cabergoline (usually better tolerated and longer-lasting)
• Pergolide (less commonly used now)

Each dopamine agonist varies slightly in terms of effectiveness, side effects, and cost, and a health professional can help decide which is the best for an individual.³

Bromocriptine

Bromocriptine is a medication that helps lower high prolactin levels.³ Bromocriptine mimics the action of dopamine.³

 Prolactin levels usually drop within the first few days or weeks of starting treatment.³ In earlier studies, prolactin levels normalised in 80–90% of patients with small tumours (microadenomas), and about 70% with larger ones (macroadenomas).^3,5 Recent studies show slightly lower success rates, especially when compared with newer medications.³

Its effect on fertility and pregnancy?

Bromocriptine is often used to help women with high prolactin regain fertility.^3,5 It is considered safe during early pregnancy (first 4–6 weeks) and has not been linked to higher risks of miscarriage, birth defects, or other pregnancy problems.³ Once pregnancy is confirmed, many women can stop the medication unless they have a large tumour.

How long do I need to take it?

Bromocriptine controls the tumour and prolactin levels, but does not cure the condition.³ If the medication is stopped suddenly, prolactin levels can rise again; therefore, it is recommended to slowly reduce doses. With some individuals being able to stop the treatment after 2-5 years when prolactin has returned to normal.³

 What are the side effects?

Most of the side effects occur at the start of treatment and gradually stop. These include:

• Nausea
• Headache
• Dizziness
• Abdominal pain
• Fatigue

Less common side effects include low blood pressure, breast pain, flushing, mood changes, and rare cases of confusion or anxiety.³ If side effects are severe, doctors may consider a vaginal form of bromocriptine, which some patients tolerate better.³

Cabergoline

Cabergoline works by acting like dopamine.³ It attaches to dopamine receptors in the pituitary gland and helps lower prolactin production.^3,6

One of the biggest advantages of cabergoline is that it only needs to be taken once or twice a week, as it remains in the body for a long time due to slow release from pituitary tissue^, and strong attachment to dopamine receptors.³

How effective is it?

For small tumours or high prolactin without a tumour, cabergoline normalises prolactin in a majority of individuals, and for larger tumours, prolactin levels return to normal in most cases.³

Pergolide

Pergolide is a medication that works like dopamine, helping to lower prolactin levels in the body.³ It’s part of a group of drugs called dopamine agonists, like Bromocriptine. ³ Pergolide is much stronger than bromocriptine and only needs to be taken once a day.⁶

How effective is it?

Pergolide helps prolactin get to normal levels in most patients with small tumours (microprolactinomas) and in about 68% of those with larger tumours (macroprolactinomas).³

Is Pergolide safe in pregnancy?

Currently, there is no known research and safety data on using Pergolide during pregnancy, so it is not recommended for use by women who are trying to conceive or are pregnant.³

What are the side effects?

Pergolide can cause side effects, including:³

• Nausea
• Headaches
• Dizziness

However, the majority of individuals report some level of intolerance to the drug. Due to this, it is less commonly used, and doctors may only prescribe it if other medications aren’t working or have lots of side effects.³

Hormone replacement therapy

Oestrogen as hormonal replacement therapy

Oestrogen is a hormone, usually combined with a hormone called progestogen and is used as a treatment option for women who have high prolactin levels and small pituitary tumours (microadenomas).³

This form of treatment is used when individuals can’t tolerate or do not respond to dopamine agonist medications, or if they do not have a desire to get pregnant.³

Women with mild symptoms who are not planning a pregnancy, or those who can’t take or don’t respond to dopamine agonists and individuals seeking symptom control and hormone balance are individuals who can benefit from this therapy.³

Risks of Oestrogen as replacement therapy

There is a small risk that oestrogen therapy could cause the pituitary tumour to grow slightly, so doctors monitor patients regularly to keep an eye on this.³

Surgery

Surgery is usually not the first choice, but may be considered if:

• Medications don’t work
• An individual can’t tolerate the side effects of medications
• Individuals prefer not to take long-term medication
• There are serious complications like bleeding into the tumour or leakage of brain fluid.

How is the surgery performed?

Most tumours are removed using a procedure called transsphenoidal surgery, where the surgeon reaches the tumour through the nose and sinus area—this is minimally invasive and relatively safe.^3,7 If the tumour is very large and has grown upward into the brain area (suprasellar extension), a more complex surgery through the skull (transcranial approach) may be needed.³

What are the risks of the surgery?

While generally safe in experienced hands, surgery carries some risks:

• Hormone deficiencies occur if the pituitary gland is damaged
• Bleeding or infection (like meningitis)
• A small risk of death (less than 1%)
• Side effects are more likely in patients with larger tumours

Fertility outcomes in CFS

With the right treatment therapy, patients can restore their menstrual cycle and have a chance at becoming pregnant.

How soon will my periods and ovulation return?

Most women begin ovulating again within 1 to 3 months after starting treatment with medications like bromocriptine or cabergoline. These medicines help lower prolactin levels, which allows your body to start producing the hormones needed for regular menstrual cycles and ovulation.³ With medical treatment, around 70% to 85% of women can conceive naturally.³

Summary

Chiari-Frimmel syndrome (CFS) is a condition that is caused by abnormal prolactin production, leading to symptoms such as amenorrhoea, galactorrhoea and the absence of ovulation seen in women postpartum. There are 3 main forms of treatment: dopamine agonists (Bromocriptine, Cabergoline and Pergolide), hormonal therapy with hormones such as oestrogen and progesterone and in rare cases, surgery. With the correct treatment, women can have regular menstrual cycles, ovulation and increased fertility and chances of being able to conceive naturally.