What are the essential drugs for treating hyperprolactinemia?

Hyperprolactinemia is also known as hyperprolactinemia. Patients may clinically present with symptoms such as amenorrhea, lactation, frequent menstruation, oligomenorrhea, infertility, sexual dysfunction, headache, obesity, etc. Patients may therefore seek treatment in the departments of obstetrics and gynecology, reproductive medicine, andrology, breast medicine, neurology, and neurosurgery.

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 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 one year of treatment with bromocriptine, prolactin and menstrual function permanently returned to normal in 11% of women with microadenomas. After two 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 higher 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 the 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%. Plasma prolactin levels returned to normal 6 months later and the drug was gradually discontinued. 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 cannot tolerate bromocriptine, those who are ineffective in treatment, and those who relapse. The dosage range is 0.04-0.1 mg/d. The therapeutic effect is related to the dosage. For example, oral administration of 0.04 mg/d reduces PRL by more than 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 74% 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. After taking the drug, plasma GH temporarily increases, 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.

(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 the pituitary tumors shrank by 25%, 77% of the pituitary tumors shrank by more than 50%, and 45% of the pituitary tumors shrank by more than 75%. Most patients' visual fields returned to normal (Orrego, 2000).