agent which is unlikely to cause this side effect and has been used successfully in the management of prolactinomas [22]. Further potential side effects of dopamine agonists include psychological disturbances, either de novo or as exacerbations of prior psychiatric disease. Patients with hyperprolactinemia treated with dopamine agonists need to be warned about and monitored for changes in mood and behavior, impulse control disorders, depression, mania and other types of psychosis [27].
Fertility, pregnancy and prolactinoma
Women with prolactinomas who are pregnant or who wish to become pregnant should be managed with the involvement of an endocrinologist. The main issues which need addressing are hyperprolactinemia and fertility, safety of dopamine agonists, tumor growth and lactation [13].
Hyperprolactinemia and fertility
Ovulation and fertility may be restored immediately following dopamine agonist treatment, even before the first normal menstruation. The couple should be informed about that, and mechanical contraception should be advised if they do not want pregnancy that month [13].
Safety of dopamine agonists
There is considerable worldwide experience with the use of bromocriptine to induce pregnancy and during pregnancy. The incidence of miscarriage, ectopic pregnancies or congenital malformations is no higher in mothers who conceived while taking bromocriptine than in the general population [1,28,29]. Cabergoline has also demonstrated a good safety record, although the number of pregnancies studied is smaller [1,22]. Despite this, it is recommended that dopamine agonists be stopped once the first menstrual period has been missed and a positive pregnancy test is obtained [1].
Tumor growth
The incidence of clinically significant tumor enlargement during pregnancy is < 3% in women with microadenomas (tumors < 1cm in diameter) and approximately 30% in women with macroadenomas (> 1cm in diameter) [1]. Dopamine agonists can therefore be safely stopped in patients with microadenomas as soon as pregnancy has been confirmed, and the patients advised to seek urgent medical attention in the event of severe headaches or visual disturbance [1]. Continuation of dopamine agonist therapy during pregnancy may be considered in cases of macroprolactinoma or where there is evidence of tumor enlargement [1]. If dopamine agonist therapy is discontinued in women with macroprolactinomas, visual‐field testing is recommended in each trimester or more often if necessary. Routine monitoring of PRL levels and MRI should not be performed during pregnancy in patients with prolactinomas, but if visual field defects or progressive headaches develop, a limited MRI without gadolinium can be performed [1].
Lactation
Women wishing to breastfeed should not be given dopamine agonists because the resulting decrease in serum PRL levels will impair lactation. There are no data to suggest that breastfeeding leads to an increase in tumor size [13].
Key points
Challenge: Hyperprolactinemia and ART treatment.
Background:
Hyperprolactinemia inhibits ovulation, causing infertility.
Treatment of hyperprolactinemia restores fertility.
Transient hyperprolactinemia during ART is not clinically significant.
Causes of hyperprolactinemia:Physiologic: pregnancy and lactation, macroprolactin, stress, excessive exercise, nipple stimulation.Pharmacologic: antipsychotics (phenothiazines, thioxanthenes, atypical antipsychotics); antidepressants (tricyclic antidepressants, monoamine oxidase [MAO] inhibitors, selective serotonin reuptake inhibitors [SSRIs]); gastrointestinal medications (metoclopramide, domperidone, cimetidine); antihypertensives (α‐methyldopa, reserpine, verapamil); estrogens; opioids.Pathologic (i) pituitary tumors; (ii) renal failure; (iii) primary hypothyroidism; (iv) polycystic ovary syndrome; (v) liver cirrhosis; (vi) chest wall lesions and trauma; (vii) idiopathic hyperprolactinemia.
Management of hyperprolactinemia:
Treat the underlying cause.
If safe, withdraw offending medication.
Dopamine agonists for pituitary tumors.
Surgery and/or radiotherapy if dopamine agonist resistance/intolerance.
It is safe to continue with bromocriptine or cabergoline during an ART cycle and until a positive pregnancy test.
Pregnancy and breastfeeding:
Monitor for pituitary tumor growth during pregnancy.
Withhold dopamine agonists in women wishing to breastfeed.
Answers to questions patients ask
1 Q1 Why haven’t you checked my prolactin level before starting our IVF treatment? A1. You have regular periods, and if the prolactin is high it will make your periods irregular or absent. So, there is no need to check the prolactin in your case. Also, we know from studies that ovarian stimulation for IVF makes the prolactin slightly high, but that does not affect the success rate.
2 Q2 Will the treatment with dopamine agonists have any effect on the pregnancy or the baby? A2. There is a lot evidence confirming treatment with the dopamine agonists bromocriptine and cabergoline is safe for both mom and baby. The incidence of miscarriages, ectopic pregnancies or congenital malformations is no higher in mothers who got pregnant while taking bromocriptine or cabergoline than in the general population [1].
3 Q3 Will I be able to breastfeed? A3. In cases where treatment is stopped following conception, patients are able to breastfeed as normal, but not in cases where treatment is continued throughout pregnancy. There is no evidence to suggest that breastfeeding leads to an increase in tumor size.
References
1 1 Melmed S, Casanueva FF, Hoffman AR, et al. Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011; 96:273–88.
2 2 Saleem M, Martin H, Coates P. Prolactin Biology and Laboratory Measurement: An Update on Physiology and Current Analytical Issues. Clin Biochem Rev 2018; 39:3–16.
3 3 Voogt JL, Lee Y, Yang S, et al. Regulation of prolactin secretion during pregnancy and lactation. Prog Brain Res 2001; 133:173–85.
4 4 Evers JL. Female subfertility. Lancet 2002; 360:151–9.
5 5 Chen AX, Burt MG. Hyperprolactinaemia. Aust Prescr 2017; 40:220–4.
6 6 Pattinson HA, Taylor PJ, Fleetham JA, Servis SA. Transient hyperprolactinemia has no effect on endocrine response and outcome in in vitro fertilization (IVF). J In vitro Fert Embryo Transf. 1990; 7(2):89–93.
7 7 Hofmann GE, Denis AL, Scott RT, Muasher SJ. The incidence of transient hyperprolactinemia in gonadotropin‐stimulated cycles for in vitro fertilization and its effect on pregnancy outcome. Fertil Steril. 1989; 52(4):622–6.
8 8 Gonen Y, Casper RF. Does transient hyperprolactinemia during ovarian hyperstimulation interfere with conception or pregnancy outcome? Fertil Steril. 1989; 51(6):1007–10.
9 9 Piekos MW, Binor Z, Rawlins RG, Radwanska E. Effects of induced hyperprolactinemia on in vitro fertilization cycles. Fertil Steril. 1995; 63(2):371–6.
10 10 Holt RI. Medical causes and consequences of hyperprolactinaemia. A context for psychiatrists. J Psychopharmacol 2008; 22:28–37.
11 11 Molitch ME. Drugs and prolactin. Pituitary 2008; 11:209–18.
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