Sexual Function and Depressive Symptoms in Young Women With Hypoprolactinemia

Robert Krysiak; Karolina Kowalcze; Bogusław Okopień

Disclosures

Clin Endocrinol. 2020;93(4):482-488. 

In This Article

Discussion

The major finding of our study was that hypoprolactinaemia disturbed libido and arousal in women, as well as resulted in the development of mild depressive symptoms. Sexual dysfunction and depressive symptoms correlated with the degree of prolactin deficiency. Moreover, cabergoline dose reduction, resulting in prolactin levels within the reference range, normalized sexual drive and arousal, which was paralleled by the improvement in mood. The obtained results cannot be explained by age, body mass index, smoking, physical activity, education, occupational activity, a type of work, the number of sexual partners, the number and duration of marriages, the number of deliveries and miscarriages, stress exposure and blood pressure, all of which were similar in the study groups. They cannot be also a consequence of differences in disorders responsible for prolactin excess, cabergoline dose and treatment duration. In light of reports that dopamine agonists induced hypersexuality in men,[7–10] our findings seem a bit surprising, indicating sex-dependent diversity in the impact of dopamine agonists on sexual functioning. From a sexual point of view, the obtained results suggest that subnormal prolactin levels should be avoided, particularly in women with additional risk factors for developing sexual dysfunction.

Compared with hyperprolactinemic subjects,[1] the total FSFI score and domain scores in women with low levels of this hormone were less affected, suggesting that excessive prolactin secretion or reduced hormone metabolism pose a greater risk of developing sexual dysfunction than lactotrope hypofunction. The obtained results are in line with previous reports of our research group showing that unfavourable effects of mild endocrine disturbances on sexual functioning were limited either to impaired sexual drive (macroprolactinaemia[1] and vitamin D insufficiency[15]) or to both impaired sexual desire and impaired arousal (euthyroid autoimmune thyroiditis[16]). Based on these findings, it seems likely that libido and sexual arousal are more susceptible to the impact of hormonal disturbances than the remaining domains of female sexual functioning.

Another interesting finding of our study is that the unfavourable effect on sexual function was partially mediated by reduced testosterone production. Moreover, apart from normalizing serum prolactin concentrations, the improvement in sexual desire and arousal was paralleled by the increase in total testosterone and the free androgen index, regarded as an estimate of biologically active testosterone.[17] The association between abnormal testosterone production and a deteriorating effect of hypoprolactinaemia on female sexual functioning is also supported by the fact that sexual drive and arousal are regulated in women by testosterone in a greater degree than the remaining aspects of female sexual functioning.[18] Unlike testosterone, estradiol levels were similar in all study arms, did not correlate with sexual functioning and were not affected by the cabergoline dose reduction-induced increase in prolactin levels. Therefore, estradiol does not seem to mediate the impact of hypoprolactinaemia on libido and arousal. For similar reasons, impaired sexual functioning cannot be explained by the impact of hypoprolactinaemia on the secretory function of either pituitary gonadotropes or the adrenal reticular zone.

The lack of similar studies in women makes it difficult to explain the mechanisms underlying low testosterone levels in females hypoprolactinaemia. However, in males, hypoprolactinaemia was found to reduce testosterone levels and to impair maximum responses of plasma testosterone to human chorionic gonadotropin stimulation.[19] Moreover, testosterone levels below the reference range were observed in as many as 67% of male subjects with hypoprolactinaemia.[20] These low testosterone concentrations in hypoprolactinemic men are probably secondary to a reduction in the number of testicular LH receptors, found in bromocriptine-treated hypoprolactinemic animals but not observed in rodents receiving both bromocriptine and exogenous prolactin.[21] It is possible that analogous interactions occur in women.

The current study has also shown that hypoprolactinaemia increased the prevalence of mild mood disturbances. This finding is in line with the results of the study by Depue et al,[22] who observed decreased prolactin levels in women with seasonal affective disorder in comparison with healthy controls. Our study excluded antipsychotic-treated subjects, while baseline characteristics of all study arms were similar. Therefore, the obtained results cannot be related to differences in sociodemographic characteristics of the study groups. The presence of correlations between the FSFI score and domain scores for libido and arousal and the overall BDI-II score and the percentage of patients with total and mild depressive syndromes as well as of analogous relationships between the improvement in sexual functioning and in depressive symptoms after cabergoline dose reduction suggests that sexual dysfunction and impaired mood in the investigated population of hypoprolactinemic women were associated with each other. The obtained results do not allow, however, to conclude whether reduced sexual drive and impaired arousal are secondary to mood disturbances or their presence, in addition to the increased body mass index, physical inactivity, stress exposure and increased values of blood pressure, contributes to the development of depressive symptoms. At first glance, hypoprolactinaemia-induced deterioration in well-being seems surprising. Enhanced dopaminergic transmission in the mesolimbic system activates the reward system, and this mechanism is suggested to contribute to the development of impulse control disorders in men managed with dopamine agonists.[23] It cannot be excluded that the discrepancy between our study and previous male studies[9,10] may be, at least partially, associated with sex-dependent differences in central dopaminergic transmission. In line with this explanation, brain distribution of D2/D3 receptor binding was sex-dependent,[24] while dopamine release and metabolism in the mediobasal hypothalamus were lower in female than male rat foetuses.[25]

Several study limitations deserve mention. Although the number of participants exceeded the required sample size, this research should be regarded as a pilot study and our preliminary findings have to be confirmed by larger multicenter trials. Because the study included only premenopausal women, it is uncertain whether hypoprolactinaemia affects sexual functioning in postmenopausal women. The accuracy of both questionnaires is limited by their subjectivity. Finally, the question of whether hypoprolactinaemia secondary to the organic destruction of pituitary lactotropes is associated with the same sexual disturbances as cabergoline-induced hypoprolactinaemia remains unanswered.

Summing up, women with cabergoline-induced hypoprolactinaemia were characterized by impaired sexual drive and impaired sexual arousal, not observed in cabergoline-treated and cabergoline-naive women with serum prolactin levels within the reference range. This unfavourable effect, which was accompanied by lower total testosterone levels and lower values of the free androgen index, disappeared when prolactin levels returned to the reference range. The obtained results indicate that hypoprolactinaemia makes women more susceptible to the development of sexual dysfunction and to mild depressive syndromes. These disturbances are reversible and seem to result from lactotrope hypofunction, but not from specific properties of cabergoline.

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