Effects of Pharmacologically Induced Hypogonadism on Mood and Behavior in Healthy Young Women

Abstract

Objective The relationship between depression and estrogen withdrawal remains controversial. The authors examined the effects of gonadotropin-releasing hormone agonist-induced ovarian suppression on mood, sleep, sexual function, and nighttime hot flushes. They focused on whether participating women experienced clinically significant depressive symptoms and whether specific symptoms associated with hypogonadism (nighttime hot flushes and disturbed sleep) increased susceptibility to depression. Method Participants were 72 healthy pre-menopausal women, ages 19–52 years, with no current or past axis I psychiatric diagnosis or gynecological or other medical illness. After 2 months of baseline screening, women received monthly injections of leuprolide acetate (3.75 mg) for 2–3 months. Outcomes were measured using the Beck Depression Inventory (BDI) and a daily rating scale measuring the severity of several affective and behavioral symptoms. Data were analyzed by repeated-measures analysis of variance using PROC MIXED (for mixed models). Results BDI scores ≥10 were reported in four of the 72 women (5.6%). Relative to baseline, induced hypogonadism was associated with significantly decreased sexual interest, disturbed sleep, and more severe nighttime hot flushes, but no significant change in any mood-related symptom score. Hot flush severity was significantly correlated with disturbed sleep. Conclusions These data demonstrate that clinically significant depressive symptoms were rare accompaniments of short-term estradiol withdrawal and induced hypogonadism in healthy premenopausal women. Additionally, neither nighttime hot flushes nor disturbed sleep were sufficient to cause depressive symptoms in hypogonadal women.

Sex differences in visuospatial abilities persist during induced hypogonadism

“…None of the women or men reported day or night hot-flushes at baseline. Otherwise consistent with previous reports in these samples of healthy volunteers, Lupron administration was tolerated without the onset of significant mood or behavioral symptoms (Ben Dor et al, 2013; Schmidt et al, 2013; Schmidt et al, 2009). Plasma sex steroid levels during GnRH agonist-induced hypogonadism were consistently suppressed at the time of testing in all men and women relative to baseline conditions.…”

“…Nonetheless, it is possible that our study was not of sufficient duration to identify the longer-term effects of hot-flushes and the accompanying sleep disturbance on cognitive function in the tasks we measured. Similarly, in healthy volunteers, studies report only minor changes in mood or behavior in men and women (Ben Dor et al, 2013; Schmidt et al, 2013; Schmidt et al, 2009) receiving Lupron. Thus, we did not observe nor did we anticipate that the emergence of adverse mood symptoms would significantly impact cognitive performance in the participants of this study.…”

Role of Serotonin Transporter Changes in Depressive Responses to Sex-Steroid Hormone Manipulation: A Positron Emission Tomography Study

“…However, notably not through the hypogonadal state per se, since remitted PPD patients also experienced depressive symptoms in the replacement phase of the intervention where their sex-steroid hormone levels were elevated. Further, a study in healthy premenopausal women indicated that depressive symptoms emerging from pharmacologically induced sex-hormone changes (4 of 72 women) were not attributable to hypogonadism itself but were coupled to the initial stimulatory component of the GnRHa response (57).…”

Perimenstrual Exacerbation of Symptoms in Borderline Personality Disorder: Evidence from Multilevel Models and the Carolina Premenstrual Assessment Scoring System

“…Although most females do not show clinically significant menstrual cycle effects on emotional (Schwartz et al 2012;Ben Dor et al 2013;Hengartner et al 2017) or cognitive Leeners et al 2017) symptoms, experiments demonstrate that a subset of females suffer from abnormal sensitivity to normal ovarian steroid changes. This hormone sensitivity manifests as emotional, cognitive, and behavioral changes appearing only or primarily in the context of normative ovarian steroid changes, such as the midluteal and perimenstrual cycle phases, as in PMDD (Schmidt et al 1998) or perimenstrual exacerbation (PME) of symptoms related to a chronic underlying disorder; during pregnancy and postpartum (Bloch et al 2000); and during the menopause transition (Schmidt et al 2015;Gordon et al 2016).…”