Introduction

Chiari-Frommel syndrome is a rare postpartum condition and endocrine disorder that is characterized by the over-production of breast milk, lack of ovulation and irregular or absent menstrual periods.¹ Patients who experience these symptoms for more than 6 months should be evaluated for this disorder. The exact causes of this condition are not fully understood, but some research suggests an abnormality of the hypothalamus or pituitary glands.²

Studying the various historical perspectives and observations of Chiari-Frommel Syndrome can provide valuable insight into how modern endocrinology has developed. From studying the history of this syndrome, we can see how early clinical observations gradually led to a clearer understanding of hormonal regulation, particularly the role of prolactin. This article will explore the history of Chiari-Frommel Syndrome, from its initial clinical descriptions in the 19th century to its current classification within reproductive endocrinology. It will aim to highlight challenges that researchers faced in diagnosing and differentiating the syndrome and the developments in treatments and pathology that helped us gain a better understanding of this and other similar disorders.

19^th-century understanding

The earliest known study exploring the symptoms of the syndrome was in 1832. Chiari and his colleagues, Braum and Spaeth, described a clinical syndrome consisting of an absence of the menstrual period, discharge of milk unrelated to pregnancy, and a shrinking of the uterus and ovaries post-childbirth. Chiari believed it was due to uterine atrophy and described it as a clinical syndrome in 1855.³ 

In 1882, a German gynecologist called Frommel developed upon this and explored uterine atrophy (the decrease in uterus size).⁴ He investigated 3000 women in labour and during the period immediately after childbirth. He stated that the average age of patients presenting symptoms of the syndrome was 29.6 years. He found that the patients coming to the physicians wanted to be consulted not because of a lack of menstruation, but because of complaints and symptoms like backache, abdominal pain and mental distress. He concluded that women may experience uterine atrophy after undergoing consecutive pregnancies in a short amount of time; this is because it puts a lot of strain on the genital organs. He suggested that uterine atrophy is caused by prolonged lactation.⁵

These two publications were then brought up by Schiller in 1932, and the condition was then officially termed Chiari-Frommel syndrome.⁴ Since then, there have been more investigations and cases that have helped contribute to our understanding of this syndrome. 

One example of a case was a 19-year-old who delivered a male child on January 12, 1953. Though the pregnancy was relatively normal, she observed a weight gain of 41 pounds and milk discharge during the third trimester. Additionally, after pregnancy, she continued producing breast milk, and her menstrual cycle had not resolved. She also made complaints of severe incapacitating right-sided headaches, often associated with nausea, vomiting. Tiredness and malaise, and denied any visual disturbances in vision. When a physical examination was taken, her neck was full, but no definite thyroid enlargement could be palpated; her chest and heart were normal. Thick, white, milky secretion could be easily expressed from her nipples. During her session, she was prescribed cyclic estrogen-progesterone medication; this helped slow down milk secretion and induced withdrawal periods. She was also prescribed gonadotropin.³

However, with these cases have also come confusion between other conditions. This is mainly explained by the lack of understanding of hormonal regulation and the discovery of important hormones, such as prolactin. A syndrome that was difficult to distinguish between Chiari–Frommel syndrome, due to its similar characteristics, is Ahumada-del Castillo syndrome. Ahumada-Del Castillo syndrome, like Chiari–Frommel syndrome, is a rare endocrine disorder affecting adult females.⁶ It is a condition which, like Chiari-Frommel syndrome, is characterized by lactation and an absence of menstruation. It involves a deficiency in estrogen levels and decreased urinary gonadotropin levels. Research has also suggested that it may involve a disruption in the hypothalamus-pituitary axis.⁷ 

These overlapping symptoms between the two disorders may explain why they were difficult to differentiate. Additionally, nowadays, we know that a key difference between the two disorders is that Chiari-Fremmel syndrome occurs in women who have just given birth. In contrast, Ahumada-Del Castillo syndrome is not associated with pregnant women or lactation. However, the hormone that induces milk production, prolactin, and concepts of pituitary tumours were not discovered until the 20th century, so researchers would’ve been unable to carry out blood hormone tests that would’ve presented this distinction between the two conditions. Thankfully, due to developments in the 20^th century regarding pituitary imaging and prolactin physiology, we can now identify the difference between the two. 

20^th-century developments

A major development in the study of this order emerged in the 20^th century; this was the discovery of prolactin. Prolactin is a hormone essential for milk production and breast development produced by the pituitary gland. Prolactin was identified in 1928 by Stricker and Grueter when they found that extracts of this pituitary hormone induced milk production in rabbits.^8,9 They found that human prolactin plays a crucial role in milk production and pregnancy.⁸ In Chiari-Fremmel syndrome, the pituitary gland or the hypothalamus is thought to be dysfunctional. This often leads to excessive prolactin secretion due to factors like microscopic pituitary tumours or impaired hypothalamic inhibition. This discovery and development of prolactin assays and imaging help researchers clearly differentiate between other similar conditions, such as Ahumada del Castillo syndrome and Forbes-Albright syndrome. 

More developments were made in the late 20^th century as diagnostic tools and modern treatments improved. By the early 21st century, significant advances in both diagnostic tools and treatment greatly enhanced our understanding of Chiari-Frommel Syndrome. One notable development was the discovery of bromocriptine. Bromocriptine is a derivative of ergot alkaloid and a dopamine agonist.¹⁰ It acts upon the pituitary and blocks the production and release of prolactin, which can be overproduced when a tumour is present in the pituitary gland. It was first discovered in 1965 at Sandoz and officially patented in 1968.¹¹

 Furthermore, the development and implementation of neuroimaging techniques, such as CT and MRI, in the early 1980s helped researchers finally observe and visualize the pituitary gland, revealing microadenomas (tumours) or enlargement that helped explain the persistent lactation in patients with the syndrome. These advances facilitated clearer differentiation from conditions like Forbes-Albright Syndrome, reducing historical diagnostic confusion. All these developments helped identify Chiari-Frommel Syndrome as a distinct endocrine disorder. They helped us better understand the hormonal mechanisms behind postpartum lactation and amenorrhea (lack of menstruation), and contributed to our broader understanding of pituitary function, postpartum function, and reproductive endocrinology.

Modern understanding of chiari-frommel syndrome and current treatment

Chiari-Frommel syndrome was reclassified under a broader category of disorders called hyperprolactinemia disorders. The term hyperprolactinemia describes disorders with elevated levels of prolactin. It was reclassified because it is now understood that the symptoms that characterize the disorder (such as elevated milk production and absence of menstruation) are caused by elevated levels of prolactin.¹³

Currently, there are a few treatments that can be implemented to help combat Chiari-Frommel syndrome. One treatment is prescribing bromocriptine, which can decrease levels of prolactin. It may also help tackle and restore irregular menstrual cycles. If there are any abnormalities associated with the hypothalamus or the pituitary gland, specific treatment is done to tackle those issues. Additionally, if symptoms persist for a long period of time, then the patient should be monitored, via CT scan or MRI, to check if a pituitary tumour is present.¹ This is because a tumour can be difficult to treat if it is very small. Surgery may not be able to be carried out on microscopic tumours found in the pituitary gland. In contrast, larger pituitary tumours can be easily removed with the help of surgical excision.²

Summary

• Studies of this syndrome and its symptoms first emerged in the 19^th century by Johann Baptist Chiari. This study was expanded upon by Frommel, who studied the decrease in uterus size
• Early on, it was often confused with conditions like Ahumada-del Castillo syndrome. This is because pituitary pathology was not fully understood, and our knowledge of modern endocrinology was not yet fully developed
• As our knowledge in endocrinology evolved, our knowledge of the pituitary gland and its hormones became more sound. More notably, prolactin was identified as a key hormone contributing to lactation and reproductive function
• Developments in diagnostic tools, such as serum prolactin and CT and MRI neuroimaging, and laboratory testing, enabled us to be able to differentiate Chiari-Frommel syndrome from related conditions such as Forbes-Albright and Argonz del Castillo syndrome
• Bromocriptine and cabergoline treatments were developed
• “Chiari-Frommel Syndrome” became reclassified under the broader category of hyperprolactinemia disorders. This is now used mainly in historical or academic contexts