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

Materials and Methods

Study Population

The participants were recruited among 50 premenopausal women (aged 18–45 years) with normal, regular menstrual cycles, who, because of hyperprolactinemia, had been treated with cabergoline (0.5–2 mg weekly) for at least 6 months before the beginning of the study. After excluding 10 normally menstruating subjects with mildly elevated prolactin levels, the study population was divided into two groups. Group A included 15 women with cabergoline-induced hypoprolactinaemia, defined as serum prolactin levels below 5 ng/mL, while group B consisted of 25 individuals with prolactin levels within the reference range (5–25 ng/mL). These two groups were compared with 30 age-matched dopamine agonist-naïve normoprolactinemic women, serving as a control group (group C). The sample size in each group exceeded the required number identified by power analysis.[1] Only patients unaware of their endocrine status were included. To minimize the impact of seasonal fluctuations on the obtained results, 35 women were enrolled in January or February, while the remaining ones in July or August.

Individuals were excluded if they met at least one of the following criteria: macroprolactinoma, mixed pituitary tumours, other hormonally active and non-functioning pituitary tumours, macroprolactinaemia, thyroid disorders, polycystic ovary syndrome, ovarian failure, galactorrhoea within 3 months preceding the study, kidney or liver failure, any acute or chronic disease, psychiatric problems, developmental or acquired anomalies of the female reproductive system, previous urogynaecological operations that might affect sexual function, sexual inactivity, pregnancy or lactation, as well as any pharmacological treatment (with the exception of cabergoline).

The study was designed and conducted in accordance with the principles of the Declaration of Helsinki. Written informed consent was obtained from each person, and the protocol was approved by the institutional review board.

Study Design

The dose of cabergoline in group A was reduced by 25% and remained unchanged in group B. Both groups were treated with this agent administered once or twice weekly at bedtime for the following 6 months. During this time, group C did not receive any specific treatment. Compliance was measured by tablet counts at each visit (every 6 weeks).

Laboratory Assays

Venous blood samples were collected from the antecubital vein between 7.00 and 8.00 AM after an overnight 12-hour fasting, in a quiet temperature-controlled room (24–25°C) in the first and last day of the study. They were taken in the early follicular phase (between days 2 and 5 of the menstrual cycle) after the patient had been resting in the seated position for a minimum 30 minutes. All measurements were conducted in duplicate to ensure the accuracy and reproducibility of the result by a person blinded to the patient's identity and the study design and details. Serum levels of prolactin, total testosterone, dehydroepiandrosterone sulphate (DHEA-S), estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and sex hormone-binding globulin (SHBG) were assayed by direct chemiluminescence using acridinium ester technology (ADVIA Centaur XP Immunoassay System, Siemens Healthcare Diagnostics, Munich, Germany). Free androgen index was calculated using the formula: testosterone [nmol//L] × 100/SHBG [nmol/L].

Questionnaires

Immediately after blood collection, all potential participants were requested to complete three questionnaires but only data of women fulfilling the inclusion and exclusion criteria were subjected to statistical analyses.

The first questionnaire evaluated sociodemographic characteristics of participants, who were asked about age, smoking, physical activity, education, occupational activity, profession, sexual partners, marital status, deliveries, miscarriages, stress exposure, as well as about obstetric and gynaecological history.

Then, the participants were asked to fill in a 19-item standardized multidimensional self-administered questionnaire assessing their sexual functioning. The questionnaire is divided into 6 domains: desire (questions 1 and 2), arousal (questions 3–6), lubrication (questions 7–10), orgasm (questions 11–13), satisfaction (questions 14–16) and pain (questions 17–19). Each answer was rated on a scale ranging from 0 to 5 or 1 to 5, with a higher score indicating better sexual function (0 indicates the lack of sexual activity during the last month).[11] The sum of basic points in each individual domain was then multiplied by a domain factor ratio (0.6 for desire; 0.3 for arousal; 0.3 for lubrication; 0.4 for orgasm; 0.4 for satisfaction; and 0.4 for pain) in order to obtain the final domain score (sexual desire: 1.2–6; sexual satisfaction: 0.8–6; sexual arousal, lubrication, orgasm and sexual pain: 0–6). The total FSFI score, obtained by adding all domain scores, may range from 2 to 36.[12] A score of 26.55 points or less indicated clinically significant sexual dysfunction.[11,12]

The last questionnaire, Beck Depression Inventory-II (BDI-II), consisting of 21 items assessing specific cognitive, affective and physical symptoms of depression, corresponds well to a clinical diagnosis of depressive disorders outlined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition.[13,14] The total BDI-II score is the sum of all item scores. The minimum score is 0, and maximum score is 63. The BDI-II scores of 0–13 denote no/minimal depression, scores of 14–19 denote mild depression, scores of 20–28 denote moderate depression, and scores of 29–63 denote severe depression.[13]

Statistical Analysis

All measured variables were log-transformed to mitigate the effects of the non-normal distributions. Between-group differences, as well as differences between per cent changes from baseline after adjustment for baseline values (reflecting the strength of cabergoline action), were analysed using one-way analysis of covariance followed by Bonferroni post hoc tests after consideration of age, smoking, body mass index and blood pressure as potential confounders. One-way within-subjects analysis of covariance followed by Student's paired t test was applied to compare pre-, inter- and post-treatment values within the same study arm. The proportional data were compared using the χ 2 test. Correlations were determined using the Pearson partial correlation coefficient (r). Statistical significance was defined as P-value corrected for multiple testing using Benjamini and Hochberg's false discovery rate less than .05.

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