Depression as adverse effect of Hormonal contraception

Few studies focused on the depressogenic properties of the hormonal contraceptives(HC)  in spite of diffuse concern about mood changes(1). Several years   ago,it   was   affirmed   that   most   women   using   combined   oral contraceptives(COCs)  can expect minimal change in mood(2).

Furthermore,  the percentage of women who reported depressive symptoms seems to decline as the number of years of HCs use increase (3). Impairment of social functioning is a significant aspect of depression distinct from the symptoms of depression (4).

Cognitive –emotional factors including the appraisal of stress, loci of control and self-integration were implicated with specific patterns of negative affect and much more so for users than for nonusers (5).

A study carried by Parry in 2001 hypothesized that changing reproductive hormones, by affecting the synchrony or coherence between components of the circadian system,may alter amplitude or timing relationships and thereby contribute to the development of mood disorders in predisposed individuals(6).  It is known that neuroactive steroids as the gamma-aminobutyric acid receptor agonists are important in the modulation of affect and adaptation to stress(7).

A recent study reported that healthy women without underlying mood or anxiety disorder who were given a low-dose combined oral contraceptives did not experience adverse psychological symptoms despite a significant reduction in neuroactive steroids. Women have the greatest risk for developing depressive disorders compared with men.

In addition several biological conditions may be involved in the predisposition of women to depression, including genetically determined vulnerability,  hormonal fluctuations, and a particular sensitivity to such hormonal fluctuations in brain systems that mediate depressive states. Although considering cognitive-emotional functioning for HCs users and non users seems that the use may influence the saliency rather than the nature of cognitive-emotional pattern (5)

Relational events as role-stress,  sex-specific socialization and disadvantaged social status have been considered to be contributors to the increased vulnerabiliuty of women to depression.

In addition,it is known that a higher proportion of housewives than women going out to full-time work show depressive symptoms. It is hypothesized that several reproductive events may be related to depression as:  premenstrual dysphoric disorder, pregnancy, post-partum, menopause, miscarriage, infertility, hormone replacement therapy and hormonal contraceptive use (8,9).

A recent study performed on adolescent girls treated with depot-medroxyprogesterone acetate (DPMA)  over a period of 12 months,  showed that those do not present depressive symptoms (10).

Similar results were obtained by an australian study carried out on 9.688 young women,aged 22 to 27 years, taking combined oral contraceptives.  In fact,  the odds ratio of nonusers experiencing depressive symptoms is not significantly different from that of COC users (OR=0.90-1.21)(3). Another study reports that combined oral contraceptive(COC) users have more negative mood impact than vaginal ring users as well as, irritability is more frequent in COCs containing low-doseEE than in COCs containing very low-dose   EE.

However,  irritability   decreases   with   duration   of   pill-use (11). Besides,sporadic cases of panic attacks,  in women who had previously experienced depression, have been reported. However, these reports regarded the combined oral contraceptives containing high doses of ethinylestradiol(50 mcg) and appeared when these users had stopped taking the pill (12). While, a recent study has demonstrated in adolescent girls taking COCs,  higher prevalence of positive mood than in MPA users (13).  The problem of whether or not oral contraceptives affect the psyche function of the woman is still controversial.

Furthermore,  the widespread presence of the depression in the industrialized countries increases the difficulty. Although the major problems found in the clinical trials were selection bias, poor assessment of preexisting mood status and unclear definition and/or measurement of depression.

Rosa Sabatini and Raffele Cagiano
Department of Obstetrics and Gynecology
Department of Pharmacology General Hospital Policlinico-University of Bari, Italy


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