Overview 

Chiari-Frommel Syndrome (CFS) is a rare hormonal disorder that affects people after childbirth and involves an absence of regular menstrual periods.¹ A classification of oral medication called Dopamine Agonists can effectively help to stop symptoms and restore hormone levels.² This article will explore how and why these treatments work, as well as practical considerations during treatment.

What is chiari-frommel syndrome?

Chiari-Frommel Syndrome is characterised by high levels of a hormone called prolactin in the blood, which is responsible for breast development and milk production. Prolactin is increased during pregnancy to support breastfeeding, but it doesn’t return to normal levels in patients with CFS.³ A high level of prolactin in the blood is otherwise known as hyperprolactinemia, and is distinguished as being more than 500 ml U/L. This leads to the overproduction of milk (galactorrhoea). Hyperprolactinemia decreases a hormone called GnRH,³ which is needed for the production of oestrogen and progesterone.⁴ In turn, these high prolactin levels and decreased oestrogen and progesterone can lead to an absence of menstrual periods (amenorrhoea) and stop ovulation (anovulation). These symptoms last well after childbirth, with milk production persisting for at least six months after weaning (stopping breastfeeding).¹ If someone born a female sees a lack of periods or irregular periods, it can be difficult to track their fertile days. If there is a lack of ovulation, it is not possible to get pregnant.

What causes chiari-frommel syndrome?

Any process that interferes with the production of dopamine, its transportation to the pituitary gland, or its action on the lactotroph can cause hyperprolactinemia - these can include stress, hypothyroidism, or certain medications. The most common cause of persistent high prolactin levels is a type of benign tumour called a prolactinoma.⁴ However, Chiari-Frommel Syndrome refers specifically to high prolactin levels after pregnancy, so prolactinoma and drug-induced hyperprolactinemia are first ruled out before Chiari-Frommel Syndrome is considered.¹

During pregnancy, prolactin levels rise sharply to help induce breast milk production. After weaning, dopamine usually signals to the brain to switch off prolactin production. In Chiari-Frommel Syndrome, this ‘off-switch’ fails, and prolactin levels remain high long after weaning. ^{3, 5}

How can dopamine agonists help?

Prolactin is produced and released from a part of the base of the brain named the anterior pituitary gland by special cells called lactotrophs.² Prolactin is packaged into small bubbles, which are known as secretory vesicles in the lactotrophs.⁵ The secretory vesicles are carried to the edge of the cell, where the membrane of the vesicle merges with the cell membrane and the prolactin is pushed outside the lactotroph and into the bloodstream. This process is called exocytosis: it requires energy to perform and is triggered by a form of Calcium.^6,7

Prolactin’s release is regulated by the hypothalamus, another part of the brain located just above the pituitary gland.² The hypothalamus releases the hormone dopamine, which acts like a brake on prolactin production. It travels to the pituitary gland and binds to lactotrophs on their D2(dopamine) receptors. This activates a cascade of activity that leads to Calcium being blocked from entry to the cells, thus inhibiting the release of prolactin into the bloodstream via exocytosis and reducing prolactin levels.^5,7

Dopamine agonists are drugs that mimic the inhibitory effect of Dopamine and bind to D2 receptors on lactotrophs to reduce prolactin levels. The most commonly prescribed are Bromocriptine and Cabergoline, which are both derived from a type of fungus called ergot.^8,9

Bromocriptine 

Bromocriptine is the first dopamine agonist ergot derivative to be used in clinical practice.¹⁰ It binds to and stimulates the lactotroph D2 receptors and inhibits the release of prolactin. It also stops the gene expression of prolactin, resulting in a decrease of prolactin synthesis.^9,10 Bromocriptine generally works well and is tolerated well, but some reported side effects include nausea, headache and dizziness.⁹ Bromocriptine is strongly attracted to D2 receptors, which is why it is effective in decreasing prolactin levels, but it also has an attraction and stimulates other receptors in the body, like D3 receptors. This could be the reason some people experience side effects. Bromocriptine has a half-life of 2-8 hours, which is the time it takes for the drug amount in our system to reduce by half, and it is taken once daily.⁹ 

Cabergoline

Cabergoline is a newer dopamine agonist and is also derived from the ergot fungus. It is reported to be more effective in normalising prolactin levels and returning to regular menstrual and ovulatory cycles, as well as stopping the overproduction of breast milk, than Bromocriptine^{2, 11} in a study with close to 500 women with hyperprolactinemia, 83% of the women on cabergoline treatment saw stable prolactin levels compared to 52% of the women taking bromocriptine.¹⁰

Cabergoline has a strong attraction to D2 receptors, and crucially, it has a low attraction to other receptors. This means that it only binds to D2 receptors and it has fewer and less severe side effects than Bromocriptine. It also has a longer duration of action than Bromocriptine and is only given once or twice a week, whereas Bromocriptine is taken once a day.² Cabergoline is the preferred dopamine agonist treatment, except during pregnancy, where Bromocriptine is favoured.²

Considerations 

While there is more data available for bromocriptine, as it is the older drug, there is a need for more research and clinical trials for both bromocriptine and cabergoline, as most of the data is extrapolated using trials for treating prolactinoma.

FAQs

Which is better - bromocriptine or cabergoline?

Both dopamine agonist treatments work, but cabergoline is often more effective and lasts longer in the body, meaning it has to be taken less frequently and is easier to use. Cabergoline also tends to produce fewer and less severe side effects. However, bromocriptine is preferred during pregnancy.²

Do I need to stay on dopamine agonist treatment for good?

Many people see their prolactin levels return to normal and their menstrual cycles resume after stopping dopamine agonist treatment.¹⁰ It is recommended to wait at least two years before tapering down or discontinuing treatment, but it does vary from person to person.¹² It is also possible for Chiari-Frommel Syndrome to resolve on its own.¹

What are the alternatives to dopamine agonist treatment?

There are medical alternatives to dopamine agonist treatment, but they require more research and testing. It is possible that a hormone called Kisspeptin could be used as an alternative. This is because when bromocriptine and cabergoline decrease prolactin levels, Kisspeptin is increased, which stops GnRH inhibition. This leads to a recovery of LH and FSH levels, and regular menstrual and ovulatory cycles are restored.¹³

Does chiari-frommel syndrome mean I can’t have children again?

Not necessarily. If Chiari-Frommel Syndrome is left untreated, it can be difficult to have children again because it can prevent ovulation. However, with the right medication, hormone levels are often brought back into balance. This restores menstrual cycles and fertility.²

Can lifestyle factors affect prolactin levels?

Yes. Stress can trigger the release of prolactin,¹⁴ and there is also some evidence suggesting that irregular sleep patterns or sleep disturbances can increase prolactin levels.15 However, spiked prolactin due to lifestyle factors is typically temporary, whereas Chiari-Frommel Syndrome causes persistently high prolactin levels.¹

Should I take dopamine agonist medication at a specific time? 

Your doctor will tell you when and how often to take dopamine agonist medication, but it has been reported that taking dopamine agonists with or after food decreases the side effects in the stomach and makes the medicine more tolerable.¹⁶

Summary 

Dopamine Agonist treatments are drugs that are used to treat Chiari-Frommel Syndrome. They are effective in reducing prolactin levels, hence stopping the overproduction of milk, returning oestrogen and progesterone to their usual levels and restarting regular menstrual and ovulatory cycles. They work by mimicking dopamine, binding to receptors on the cells that produce prolactin. 

Bromocriptine and Cabergoline are taken orally. They are both effective, but cabergoline is the preferred medication as it is slightly more effective and causes fewer and less severe side effects. Cabergoline is taken once or twice a week because it lasts longer in the body, while bromocriptine is taken once daily. Bromocriptine is preferred during pregnancy.

While there is more clinical information available on Bromocriptine, as it is older, both medications and Chiari-Frommel Syndrome require more research.