What is Prolactin?
Prolactin is a hormone also known as Lactotropin. It is a protein that enables mammals to produce milk, this mostly happens in females. When a woman is ready to give birth, her mammary gland is the target organ/ tissue, that is enabled with the help of prolactin. Prolactin is the one that tells your breasts to make more milk, another hormone, oxytocin is the one that gets the milk from your breasts to your baby. So Does Prolactin Cause Weight Gain? Find out how!
It is made in the pituitary gland, which gets the signal from the hypothalamus which secretes prolactin-producing hormone. It is a chain of reactions that causes the creation of prolactin and that makes it do its work.
Increase in Prolactin levels, Increase in body weight:
Increased body weight is associated with prolactin-secreting pituitary adenomas. Several animal studies and few human studies, especially in men, with hyperprolactinemia (HPL). However, the exact reason behind this mechanism is unclear.
Prolactin has a large variety of effects on metabolism. A combination of factors: Decreased dopaminergic tone, hypogonadism with or without associated leptin resistance, low adiponectin could contribute to weight gain.
Hyperprolactinemia stimulates food intake. Also, alterations are seen in plasma glucose homeostasis, insulin sensitivity, and lipid parameters.
It is also found that Serum lipids, postheparin plasma lipase activities, and glucose tolerance are seen in patients with prolactinoma. The serum lipid profile is checked for cardiovascular risk prediction.
Why does weight gain happen?
Studies have shown that an increased level of functional prolactin in women who are not pregnant or breastfeeding can reduce the metabolism of fat which can result in weight gain. But activation of dopamine D2 receptors improve metabolic parameters of obese women.
Patients with elevated PRL levels on at least two occasions and magnetic resonance imaging (MRI) evidence of pituitary adenoma were included.
Obesity Research shows that Increased body weight is associated with prolactin-secreting pituitary adenomas. These pituitary adenomas have an unregulated and continuous secretion of the hormone prolactin. The high levels of prolactin that is hyperprolactinemia, have a different effect on women and men.
Receptor Gene Expression
Prolactin and growth hormone regulate adiponectin secretion and receptor expression in adipose tissue. Large tumors can compress surrounding structures, primarily the normal pituitary gland and optic pathways, causing symptoms. The symptoms that result from the compression are independent of the effects of excess growth hormone secretion.
Obesity may be related to a prolactinoma, although uncommon, and can lead to adverse effects like insulin resistance and metabolic syndrome.
Recent research suggests that hyperprolactinemia causes an abnormal lipid profile, weight gain, and cardiovascular diseases. Moreover, high prolactin levels lead to decreased testosterone production by disrupting 17-b-estradiol synthesis.
Increased prevalence of high Body Mass Index in patients presenting with pituitary tumors and severe obesity in patients with macroprolactinoma we noticed. To reduce this subsequent weight loss treatment with dopamine agonists has also been suggested.
Bodyweight due to Prolactinoma:
Quite many studies have shown that patients with prolactinoma have higher body weight than those who have pituitary tumors. It is discussed that most of the patients had subsequent weight loss after the treatment for prolactinoma but there was one study that showed proof of weight gain after the treatment.
Case Study :
This was a study conducted by H Soran, MacFarlane, and J Wilding published in the International Journal of Obesity.
They had taken 37 patients with prolactinoma into consideration. Out of these 37, 15 had Microprolactinoma and the rest, 22 had Macroprolactinoma. Their Tumor size was defined by MRI, where prolactinomas can be detected using magnetic resonance imaging (MRI) of the pituitary gland.
The patient’s tumor size, body weight, and prolactin concentrations were taken into consideration. The patients had received a dopamine agonist.
They were all given different treatments depending on their diagnose, like surgical treatment, radiotherapy, growth hormone replacement therapy, thyroxine, hydrocortisone, and sex hormone replacement.
It was noticed that the initial body weight of patients with macroprolactinoma was higher than that of the patients with macroprolactinomas. Most of these male patients and were average older than those with microadenomas.
During the initial consultation, only two patients had complained about recent weight gain. This was despite the decrease in serum prolactin concentration after the treatment.
This study proved that the weight fluctuations after treatment are not related to the serum prolactin concentration of the treatment given to the patients. And there is no relationship found between change in body weight and circulating prolactin concentration.
This proved that Hyperprolactinaemia is not a reversible cause for weight gain.
Although Hyperprolactinemia has been associated with changes in body composition and metabolic abnormalities. Normalization of prolactin with dopamine agonists has been found to reverse these abnormalities.
This was the start of the research, which was proved wrong.
Case study on how Hyperprolactinemia simulates food in the female rat:
A prolactin-deficient mouse/rat has an unaltered metabolic phenotype. It is known that in rats the lactation is marked by hyperphagia. This study with rats is conducted to examine the possibility of elevated prolactin levels.
Prolactin stimulates leptin secretion by rat white adipose tissue. But this study evaluates the effects of hyperprolactinemia on brown adipose tissue and carcass composition.
Case study: Elevated prolactin
The scientists took virgin Osborne-Mendel rats. They were made hyperprolactinemic using ectopic pituitary transplants (PIT) and sham-operated (SHAM).
Gradually food ingestion, body weight, and rectal temperature were noted down daily.
After 11-12 days the rats were turned into carcasses, these were subjected to body composition analysis. It Was noticed that before the operation, both the PIT and the SHAM rats weighed the same. The post result was that the PIT rats gained significantly more weight than the SHAM rats.
They also demonstrated higher serum prolactin, to levels that are well within physiological limits, are capable of stimulating food intake and white fat deposition in the female rat. It is presently unclear whether these results are a direct or an indirect effect of hyperprolactinemia.
Hyperprolactinemia does not affect plasma ghrelin levels in patients with prolactinoma:
This is another case study that accumulates data to show that prolactin is a modulator of body weight. It also suggests that prolactin regulates some transporters in adipose tissue.
It showed that hyperprolactinemia is associated with weight gain and obesity. There is a hormone, Ghrelin, that secretes many organs including the pituitary gland. This hormone acts by regulating stimulating appetite and homeostasis.
Ghrelin is given the main role and is found if it acts as a weight gain traction in patients with prolactinoma.
Forty-four patients with prolactinoma were taken into consideration. In this group, both newly diagnosed and undergoing cabergoline treatment were included along with healthy subjects in a control group.
Their different levels were continuously measured, the serum fasting glucose, lipid profile, insulin, and ghrelin.
Patients who had prolactinoma showed significantly higher serum levels of fasting insulin, triglyceride. And they seemed to have a huge difference in their hip and waist measurements.
But, there was no difference shown between fasting glucose, high-density lipoprotein cholesterol, low density lipoprotein cholesterol, and the HOMA-IR levels. The body mass index was also higher in patients with prolactinoma than in the control group.
And there were no changes between prolactin or ghrelin levels and body fat distribution percentage.
This shows that ghrelin does not affect weight gain in patients with prolactinoma.
Metabolic abnormalities in patients with prolactinoma:
Hyperprolactinemia has been associated with changes in body metabolic abnormalities and body composition. This study is to show the anthropometric and metabolic alterations with prolactinoma and the response of these abnormalities to the cabergoline treatment.
There were 19 patients taken into consideration, they all had a prolactinoma. And 20 people were case studied who were age, gender, and mass index-matched to the prolactinoma patients.
The metabolic parameters in cases and controls were recorded. Metabolic parameters before and after cabergoline treatment and the hormonal profile of cases and controls were recorded all the time.
It showed that, Out of 19 patients, 15 had microadenoma and four had macroadenoma. Out of 18 women, one had primary amenorrhoea, 12 had secondary amenorrhoea and the other five were eumenorrheic. Four women had primary infertility and two had secondary infertility.
Patients with prolactinoma have adverse metabolic profiles when compared with matched controls. And the normalization of prolactin with cabergoline corrects all the metabolic abnormalities.
Metabolic abnormalities in prolactinoma
Many metabolic abnormalities have been described in men and women with Hyperlactinoma (HPL). Patients with HPL have insulin resistance and glucose intolerance compared to normal individuals.
In the present study, we documented higher levels of fasting plasma glucose in patients with prolactinoma compared to age, gender, and weight-matched controls.
Insulin Sensitivity and plasma glucose
Many previous case-control studies have documented higher insulin resistance and abnormal glucose tolerance in patients with prolactinoma compared to healthy controls. Prolactinoma inhibits lipoprotein lipase activity in human white adipose tissue, was used in the identification of functional prolactinoma.
In the present study, fasting plasma insulin and glucose were high in patients with prolactinoma compared to age, gender and BMI matched healthy controls implying that the diabetogenic effect of HPL may be independent of gender and body weight.
In another study, total cholesterol and LDL-cholesterol concentration were found to be higher in women with hyperprolactinemic amenorrhea compared to an age-matched control group.
The abnormal lipid profile in people with Hyperlactinoma is contributed partly by an increase in body weight and partly because of the lipogenic action of prolactinoma.
A reversible weight gain along with prolactin levels-in children:
Frequent complaints of body weight gain were absorbed with people with hyperprolactinemia this was associated with high obesity.
It was commonly known that normalization of prolactin levels results in body weight loss. But the nature of this was poorly defined. To prove this they had taken a 14-year-old female as a subject, who had primary amenorrhea and persistent progressive weight gain.
The patient was 152 cm in height, 70 kg in weight, and 30.3 kg/m2. Her serum prolactinoma level was very high and the MRI scan showed the presence of the pituitary microadenoma. A basal hormonal investigation showed normal free thyroxin, TSH, IGF-I, cortisol, and ACTH values.
Treatment with the non-selective dopamine agonist pergolide caused a significant reduction of serum Prolactinoma concentration with a remarkable decrease in body weight. And during the follow-up, a repeat MRI scan revealed the disappearance of the microadenoma.
Similarly, the reduction of the daily dose of pergolide was associated with an increase of serum Prolactinoma concentration with significant weight gain. A further reduction of body weight was subsequently observed with an increase of pergolide dosage.
This study shows that Serum Prolactonima measurement may be useful as part of the endocrine work-up of obese children with a history of unexplained recent weight gain, especially if associated with pituitary-gonadal axis dysfunction.
But the relationship between Prolactinoma secretion and weight change needed to be examined more with different and higher studies.
Significant Weight loss with normalization of prolactin levels:
For hypothyroid-related hyperprolactinemia, treatment of hypothyroidism with thyroxine will result in the normalization of prolactin levels in the body. It was also seen that raised prolactin levels in a woman who is not pregnant or breastfeeding reduce lipid metabolism also known as fat metabolism.
Normalization of prolactin (PRL) levels results in weight loss. Prolactinomas with obesity can be treated with proper medications. This is mostly done with dopamine agonist therapy.
In women, an abnormally high level can cause menstrual disturbances and infertility, and may also result in insulin resistance. In recent years scientists have also recognized the role of prolactin in the development of obesity, but only a little research has been done into the precise mechanism by which prolactin regulates metabolism.
For macroprolactinomas, surgical resection is less effective due to the invasive nature of the tumor. Surgery is usually reserved for patients planning a pregnancy, patients with visual deterioration not reversed by dopamine agonists, or those who are intolerant of medical therapy.
Treatment for the increased levels of prolactin depends on the cause. It is shown that the Normalization of prolactin levels results in immediate restoration of menstrual function and fertility in women. Subsequent weight loss after treatment with dopamine agonists has also been reported.
Recently, there has been a lot of research linking prolactinoma with insulin resistance and metabolic syndrome. Clinical endocrinology treatment options are considered for patients with Metabolic Syndrome.
Increased prevalence of high body mass index in patients presenting with pituitary tumors which show obesity in patients with macroprolactinoma.
Many signs show the presence of pituitary adenoma. The main ones depend on whether they are Functional or Non-functional, ie. if they make excess hormones or make less hormone.
They are divided into small tumors also called microadenomas, most of the time this functional type makes too much of a single pituitary hormone. And then there are the large tumors, the macroadenomas, these become big before we can notice them.
Non-functional adenomas cause no symptoms and are sometimes found because of MRI or CT scans. A few symptoms of different types of tumors and cancers are listed and explained below.
Pituitary carcinomas and Large tumors-macroadenomas:
Pituitary macroadenomas which are more than 1 cm and carcinomas which are cancers, can be large enough to press on nearby nerves or parts of the brain. Even these are functional or not.
This can lead to symptoms such as:
- Eye muscle weakness so the eyes don’t move in the same direction at the same time
- Blurred, double, or loss of peripheral vision
- Sudden blindness
- Headache and facial numbness or pain
- Can cause you to pass out.
The Macroadenomas and Pituitary carcinomas can also press on and destroy the normal parts of the pituitary gland. This causes a shortage of one or more pituitary hormones. Low levels of body hormones such as cortisol, thyroid hormone, and sex hormones cause symptoms.
Depending on which hormones are affected, symptoms might include:
Nausea, Weakness, Unexplained weight loss, or weight gain, loss of body hair, feeling cold, feeling tired or weak, Menstrual changes, or loss of menstrual periods in women. Erectile dysfunction, Growth of breast tissue, decreased interest in sex in men
Diabetes insipidus: Large tumors can sometimes press on the posterior (back) part of the pituitary, causing a shortage of the hormone vasopressin. This can lead to diabetes insipidus. In this condition, too much water is lost in the urine, so the person urinates often and becomes very thirsty as the body tries to keep up with the loss of water.
If left untreated, this can cause dehydration and altered blood mineral levels, which can lead to coma and even death. Diabetes insipidus is easily treated with a drug called desmopressin, which replaces vasopressin.
Growth hormone-secreting adenomas:
The major symptoms from these tumors are caused by having too much growth hormone (GH). These effects are quite different in children and adults.
In children, high GH levels can stimulate the growth of nearly all bones in the body. The medical term for this condition is gigantism. Signs include:
- Being very tall or very rapid growth
- Joint pain
- Increased sweating
In adults, the long bones especially in the arms and legs can’t grow anymore, even when GH levels are very high. This causes a condition called acromegaly. Signs and symptoms are:
- Growth of the skull, hands, and feet
- Deepening of the voice
- Change in how the face looks
- Wider spacing of the teeth and protruding jaw
- Joint pain
- Increased sweating
- High blood sugar or even diabetes mellitus
- Kidney stones
- Heart disease
- Vision changes
- Numbness or tingling in the hands or feet
- Thickening of tongue and roof of the mouth, leading to sleep disturbances such as snoring and pauses in breathing.
- Thickened skin
- Increased growth of body hair
Corticotropin (ACTH)-secreting adenomas:
High ACTH levels cause the adrenal glands to make steroid hormones such as cortisol. Having too much of these hormones causes symptoms that doctors group as Cushing’s syndrome. When the cause is too much ACTH production from the pituitary it’s called Cushing’s disease. In adults, the symptoms can include:
- Unexplained weight gain causing purple stretch marks on the chest or belly
- New or increased hair growth
- Swelling and redness of the face
- Extra body fat on the back of the neck
- Moodiness or depression
- Vision changes
- Easy bruising
- High blood pressure
- Decreased sex drive
- Changes in menstrual periods in women
- Weakening of the bones can even cause fractures
Prolactin-secreting adenomas (prolactinomas or lactotroph adenomas)
Prolactinomas are most common in young women and older men.
In women before menopause, high prolactin levels cause menstrual periods to become less frequent or to stop. High prolactin levels can also cause abnormal breast milk production, called galactorrhea.
In men, high prolactin levels can cause breast growth and erectile dysfunction (trouble with erections)
Both men and women can have: Loss of interest in sex, infertility, Weakening of the bones is called osteoporosis
If the tumor continues to grow, it can press on nearby nerves and parts of the brain, which can cause headaches and vision problems. In females who don’t have periods (such as girls before puberty and women after menopause), prolactinomas might not be noticed until they cause these symptoms.
Thyrotropin (TSH)-secreting adenomas:
These rare tumors make too much thyroid-stimulating hormone (TSH), which then causes the thyroid gland to make too much thyroid hormone. This can cause symptoms of hyperthyroidism:
- Rapid or irregular heartbeat
- Decreased interest in sex
- Tremors or shaking of the body
- Frequent bowel movements
- A lump in the front of the neck
- Weight loss
- Increased appetite
- Feeling warm or hot
- Trouble falling asleep
Gonadotropin-secreting adenomas: luteinizing hormone or Follicle Stimulating Hormone
These rare tumors make luteinizing hormone (LH) and/or follicle-stimulating hormone (FSH).
This can cause irregular menstrual periods in women or low testosterone levels and decreased interest in sex in men.
Many gonadotropin-secreting adenomas don’t make enough hormones to cause symptoms, so they are non-functional adenomas. These tumors may grow large enough to cause symptoms such as headaches and vision problems before they are found. They are also part of large tumors.