What to do if you have hyperprolactinemia

As for what to do if you have hyperprolactinemia, we must actively grasp it and correctly grasp it. Only symptomatic treatment can achieve good results. So what should we do if we have hyperprolactinemia? Next, we will introduce what to do if you have hyperprolactinemia.

Treatment for hyperprolactinemia

1. Anti-prolactin drugs

Antiprolactin drugs include bromocriptine, long-acting bromocriptine, tergoline, cabergoline, tergoline, methylergoline, quinagoline (nogonin), and lisuride.

(1) Bromocriptine therapy:

Bromocriptine is a semi-synthetic ergot alkaloid derivative and a dopamine receptor agonist. Bromocriptine promotes the production and secretion of hypothalamic PRI-IH and inhibits the production of pituitary PRI by enhancing the function of dopamine receptors. Bromocriptine also directly inhibits the growth of pituitary tumors and the secretion of pituitary PRI, GH, TSH and ACTH.

Bromocriptine therapy is suitable for various types of hyperprolactinemia and is also the first choice for the treatment of pituitary adenomas. The oral dose is 2.5-5.0 mg/d. The blood concentration of bromocriptine reaches its peak 1-3 hours after oral administration, and the inhibitory effect on prolactin secretion lasts for 14 hours. After taking 2.5 mg of bromocriptine orally once, prolactin levels in about 90% of patients decrease, and prolactin levels in 1/3 of patients decrease to normal. Vaginal medication can be used for those who cannot tolerate oral administration.

The purpose of bromocriptine treatment is to suppress galactorrhea, restore menstruation, and promote ovulation and pregnancy. The average treatment time for non-tumor hyperprolactinemia is 12 months, and the average treatment time for tumor hyperprolactinemia is 47 months. Univariate and multivariate analysis found that the treatment effect was correlated with age, gender, initial dose of bromocriptine, duration of treatment, tumor size, pregnancy during treatment, and previous radiotherapy.

After bromocriptine treatment of tumor-induced hyperprolactinemia, 80% to 90% of pituitary microadenomas shrink, and 10% to 20% permanently disappear, mostly within the first few weeks of treatment. After discontinuation of bromocriptine, the tumor recurrence rate is 35%. Although there is no evidence that bromocriptine has teratogenic effects and does not affect pregnancy outcomes, treatment should be stopped if pregnancy occurs during treatment.

After 1 year of bromocriptine treatment, 11% of women with microadenomas had permanent restoration of normal prolactin and menstrual function. After 2 years of treatment, the permanent regression rate of pituitary tumors was 22%. Although high-dose bromocriptine (10 mg/d) is more effective than low-dose, the side effect rate is high and difficult to tolerate. Bromocriptine (5-12.5 mg/d) can cause 50% of pituitary macroadenomas to shrink, of which 2/3 occur within 6 weeks before treatment and 1/3 shrink after 6 months of treatment. For details on the ovulation rate, pregnancy rate, dosage and efficacy of bromocriptine treatment, please refer to the anti-prolactin section.

(2) Cabergoline:

It is a long-acting, highly effective anti-prolactin preparation with good clinical efficacy and tolerability. Cabergoline has a high affinity for dopamine receptor D2, directly inhibits pituitary prolactin-secreting cells, and reduces prolactin secretion. The therapeutic dose range is 0.25-1.0 mg/week. Start with a small dose of 0.25 mg, twice a week, and change to 1 mg after 4 weeks, twice a week. 2-3 hours after taking the medicine, the blood drug concentration reaches its peak, and the plasma half-life is 65 hours. After treatment with cabergoline, 80% of patients' prolactin levels dropped to normal, the ovulation rate was 72%, and the galactorrhea cessation rate was 90%. The drug was gradually discontinued 6 months after the plasma prolactin level returned to normal. Clinical observations have shown that cabergoline is superior to bromocriptine in efficacy and tolerability, and is the first choice, safe and effective new generation of drugs for the treatment of hyperprolactinemia.

Cabergoline can significantly shrink pituitary tumors or even completely eliminate them, and can be used to treat giant pituitary adenomas that are resistant to bromocriptine. Clinical data show that although cabergoline has no adverse effects on pregnancy, once ovulation resumes during treatment, treatment should be stopped one month before the desired pregnancy.

(3) Quinagarin (Nuoguoning):

It is a non-ergot alkaloid dopamine agonist and a new generation of specific, highly effective and long-acting anti-PRL drugs. The plasma half-life is 22h. CV205-502 is a powerful dopamine receptor (D1, D2) agonist. It inhibits PRL production at the level of PRL cells in the hypothalamus-pituitary axis by enhancing dopamine receptor function. It has strong and lasting effects, good tolerance and mild side effects. Headache, dizziness, nausea, vomiting, etc. may occur at high doses. It has no adverse effects on heart, lung, liver, kidney and blood functions. Patients tolerate quinacrine well, and the chance of discontinuation due to adverse reactions is 7%, which is better than bromocriptine.

Quinacolin is used to treat patients who are intolerant to bromocriptine, those who are ineffective in treatment, and those who have relapsed. The dosage range is 0.04-0.1 mg/d. The therapeutic effect is dose-related. For example, oral administration of 0.04 mg/d reduces PRL by >50% and lasts for 8 hours; oral administration of 0.06 mg/d reduces PRL by 66% and lasts for 24 hours. It still reduces PRL by 47% after 36 hours, and the sleep PRL peak disappears. Quinacolin inhibits TSH synthesis and release, but does not affect FSH, LH, T. and adrenal axis function. Quinacolin increases the release of GH-RH and inhibits the release of GH-IH. Plasma GH temporarily increases after taking the drug, but GH remains normal at night.

Quinacolin treatment should start with a low dose, 0.025 mg per day for the first 3 days, 0.050 mg/d for the next 3 days, and then 0.075 mg/d. The dose is then adjusted based on the treatment response, reaching 0.1 mg/d in 3 months. Prolactin levels begin to decrease in most patients after 1 month of treatment, and patients tolerate it well.

After treatment with quinacrine, the average volume of pituitary giant adenomas shrank by 324 mm3 (46%), and that of microadenomas shrank by 73 mm3 (57%). The average plasma prolactin level of giant adenomas decreased by 163 μg/L (65%), and that of microadenomas decreased by 113 μg/L (73%). 107 cases were observed in 27 medical centers in France, and significant clinical efficacy appeared after 2 years of treatment. Schultz (2000) observed (50 cases, dose of 100 μg/d, average treatment of 31.6 months) that the rate of prolactin recovery to normal was 82% for non-tumor hyperprolactinemia, 73% for microadenomas, and 67% for giant adenomas. The rate of tumor volume reduction was 55% for microadenomas and 75% for giant adenomas, and vision improved or returned to normal. The pregnancy rate was 26%. Nobels (2000) found that high-dose quinacridone could not effectively inhibit the growth of non-functional pituitary tumors, and its effect may be related to the expression of dopamine receptors in the tumor.

DiSarno (2000) first used quinagoline (0.075-0.6 mg/d, 12 months), and then used cabergoline (0.5-1.5 mg/time, twice a week, 12 months). The rate of prolactin recovery to normal was 100% for microadenomas and 87.5% for macroadenomas. The tumor volume reduction rate was more than 80%, 21.7% for microadenomas and 25% for macroadenomas. All patients had recurrence of hyperprolactinemia 15 to 60 days after stopping quinagoline. Both drugs were well tolerated. Some patients may experience nausea and postural hypotension in the first week of quinagoline treatment, but the symptoms disappeared naturally in the third week of treatment.

(4) Pergolide:

It is a new generation of safe, inexpensive, well-tolerated anti-prolactin drugs. It is the first choice for the treatment of giant pituitary adenomas. The dosage is 0.05-0.5 mg/d. After 12 months of treatment (3-36 months), PRL decreased by 88%, 86% of pituitary tumors shrank by 25%, 77% shrank by more than 50%, and 45% shrank by more than 75%. Most patients' visual fields returned to normal (Orrego, 2000).

2. Ovulation induction therapy

It is suitable for patients with hyperprolactinemia, anovulatory infertility, and those who cannot successfully ovulate and become pregnant after simple bromocriptine treatment. That is, a comprehensive treatment with bromocriptine as the main ingredient and other ovulation-promoting drugs is used:

(1) Bromocriptine-CC-hCG.

(2) Bromocriptine-hMG-hCG.

(3) GnRH. Pulse therapy - bromocriptine, etc. Combined therapy can save anti-prolactin drugs, shorten the treatment cycle and improve ovulation rate and pregnancy rate.

3. Surgery

It is suitable for patients with giant adenomas that present intracranial compression symptoms, who are ineffective with bromocriptine treatment, giant adenomas, and serotonin-induced cell tumors that secrete multiple pituitary hormones. The current transsphenoidal microsurgery is safe, convenient, and easy to perform, and its efficacy is similar to that of bromocriptine therapy. The combination of bromocriptine before and after surgery can improve the efficacy. The disadvantages of surgery are that pituitary tumors have no obvious capsule and unclear boundaries, and it is not easy to be thorough or damaged during surgery, which can cause cerebrospinal fluid nasal fistula and postoperative hypopituitarism. It is worth noting that although preoperative bromocriptine treatment can shrink the tumor, it can cause tumor fibrosis, sclerosis, and adhesion of surrounding tissues, which is not conducive to surgical separation and resection. Therefore, if surgery is determined, medication can be temporarily stopped before surgery, and medication or radiotherapy can be supplemented after surgery.

The mortality rate of microsurgical resection of pituitary prolactin adenoma is less than 0.5%, the incidence of temporary diabetes after surgery is 10% to 40%, and permanent diabetes and iatrogenic hypothyroidism are less than 2%. The probability of prolactin and ovulation returning to normal after microadenoma surgery is 65% to 85%, while that of macroadenoma is 20% to 40%, and the visual field returns to normal in 85%.

4. Chemotherapy (radiotherapy)

It is suitable for non-functional tumors of the hypothalamus-pituitary system and those who have not responded to drug and surgical treatment. Currently, advanced stereo focused radiotherapy methods are mostly used, including: deep X-rays, γ, 60Co, α particles and proton rays, radionuclide 90Y, 198Au pituitary implantation, etc.