Table 2.
Sex-related differences in ADRs.
| Pharmacological Class/Drug | ADRs’ Frequency/Intensity | Comments and Conclusion | Reference | ||
|---|---|---|---|---|---|
| Results | Consistency | Type of ADRs | |||
| Morphine | F > M | A | Nausea, vomiting, respiratory depression | Gastrointestinal and respiratory ADRs are considerably more frequent in women. There are hints that cardiovascular ADRs are also influenced by sex, but the available data are scarce. | [36,37,38,39,40,41,42] |
| TCAs | F > M | B | Dry mouth, constipation, sedation, sweating, and tremor | Pharmacokinetic studies revealed that women have higher plasma levels of TCAs than men, therefore being more sensitive to side effects. | [56,78,79] |
| SSRIs | M > F | B | Sexual dysfunction | SSRIs deteriorate the sexual function precisely through: impairment in desire and arousal, inhibition of orgasm, delayed ejaculation, and male impotence. | [90,91,92] |
| Anticonvulsants | - | I | Sex-hormone-related ADRs | Generally, AEDs can lead to changes within sex hormones’ metabolism. However, since these drugs have a multitude of mechanisms of action, a general conclusion over sex-related differences cannot be drawn. | [101,112,113,114,115,116] |
| Valproic acid | F > M | B | Polycystic ovary syndrome, hyperinsulinism, hyperandrogenism, hypothalamic amenorrhea | Valproic acid has been incriminated in producing gender-related side effects, especially among women, increasing the incidence of the mentioned ADRs, apart from the acknowledged effects on offsprings. | [116] |
| CarbamazepinePhenytoinPhenobarbital | F > M | B | Alteration in bone metabolism | They increase the levels of sex-hormone-binding-globulin and decrease the levels of total serum testosterone, free androgen index, dehydroepiandosterone sulfate, and estradiol. | [112,113] |
| Antipsychotics | F > M | B | metabolic dysfunctions, cardiovascular disorders, hyperprolactinemia | Females exhibit lower fasting plasma glucose levels, elevated waist circumference and waist-to-hip ratio, prolonged QTc interval, and reduced bone density due to hyperprolactinemia. | [124,134,135,136,137] |
| M > F | C | acute dystonic reactions, tardive dystonia, akathisia | Males are generally more prone to developing extrapyramidal side effects. | [122] | |
| M = F | B | Sexual dysfunction | ADRs are due to dopaminergic antagonists (females) or drugs having α1-antiadrenergic/anticholinergic properties (males). | [138,139,140,141,142,143] | |
Legend: A—Indicated by the majority of studies; B—Indicated by many studies, although there are some stating the opposite; C—conflicting results, but there is a tendency towards the indicated direction; F—Females; M—Males; I—Inconsistent Results.