Sexual Function and Depressive Symptoms in Hypoprolactinemia

In This Article

Abstract and Introduction

Abstract

Objective: Dopamine agonist treatment may result in hypersexuality in men. The aim of this study was to investigate for the first time female sexual functioning and depressive symptoms in women with very low prolactin levels.

Design: A prospective case-control study.

Patients and Measurements: The study population consisted of three age-matched groups of young women with normal, regular menstrual cycles: 15 subjects with cabergoline-induced hypoprolactinaemia (group A), 25 cabergoline-treated individuals with prolactin levels within the reference range (group B) and 30 dopamine agonist-naïve women with normoprolactinemia. Because of low prolactin levels, the dose of cabergoline in group A (but not in group B) was then reduced. Apart from measuring serum levels of prolactin, testosterone, sex hormone-binding globulin, dehydroepiandrosterone sulphate, estradiol and gonadotropins, at the beginning of the study and 6 months later, all included women filled in questionnaires evaluating female sexual function (FSFI) and depressive symptoms (BDI-II).

Results: At the beginning of the study, there were no differences between groups B and C in the mean total FSFI score, all domain scores and in the BDI-II score. In group A, the total FSFI score and domain scores for desire and arousal were lower, while the BDI-II score was higher than in the remaining study groups. Compared with groups of B and C, women with cabergoline-induced hypoprolactinaemia were also characterized by lower total testosterone levels and lower values of the free androgen index. Cabergoline dose reduction normalized the FSFI score, desire, arousal, the BDI-II score, as well as normalized prolactin, total testosterone and the free androgen index.

Conclusions: The obtained results suggest that dopamine agonist-induced hypoprolactinaemia impairs sexual functioning and well-being in young women, as well as that these disturbances are secondary to low prolactin levels, not to specific properties of cabergoline.

Introduction

The results of a few studies accordingly indicate that chronic hyperprolactinemia may exert a negative impact on female sexual functioning. Compared with healthy counterparts, women with elevated prolactin levels were characterized by a lower total score for the female sexual functioning index (FSFI), as well as by lower domain scores for sexual desire, sexual arousal, lubrication, orgasm, sexual satisfaction and pain.^[1,2] Both the total and all domain scores negatively correlated with prolactin levels but not with the other measured hormones.^[1,2] Hyperprolactinemic women with well-defined disorders of the hypothalamus or pituitary more frequently reported impaired sexual drive, which was accompanied by an increased prevalence of disturbances in lubrication or orgasm, than normoprolactemic subjects with hypothalamo-pituitary disorders.^[3] In another study, hyperprolactinemia was diagnosed in 16.8% of women with hypoactive sexual desire disorder.^[4] Moreover, despite similar concentrations as in the control group, prolactin levels in women with polycystic ovary syndrome inversely correlated with orgasm domain score.^[5] The unfavourable effect of prolactin excess on all aspects of sexual functioning as well as on depressive symptoms was markedly alleviated by short-term bromocriptine treatment.^[6]

Recent studies have shown that in addition to gambling, binge eating and compulsive shopping, male subjects treated with high doses of dopamine agonists are characterized by hypersexuality. Compulsive sexual behaviour, initially observed in men receiving dopamine agonists because of Parkinson's disease or restless leg syndrome,^[7,8] may also develop in men with prolactin-secreting tumours and usually resolves after treatment cessation.^[9,10] Unlike men, there were no differences in the overall prevalence of impulse control disorders between dopamine agonist-treated women with prolactinoma and the control group including dopamine agonist-naïve women with non-functioning pituitary adenomas.^[10] However, the authors reported three cases of hypersexuality in women with prolactinoma but did not mention how many control women complained of increased libido.^[10] Because of the paucity of data, the aim of this study was to compare female sexual functioning and depressive symptoms in women with cabergoline-induced hypoprolactinaemia and women with prolactin levels within the reference range.

Table 1. Sociodemographic characteristics of the study population
	Group A^a	Group B^b	Group C^c
Number of patients	15	25	30
Age (years; mean [SD])	32 (7)	31 (7)	31 (6)
Body mass index (kg/m²; mean [SD])	25.0 (4.0)	24.0 (3.6)	23.8 (3.4)
Smokers (%)/Number of cigarettes a day (n; mean [SD])/Duration of smoking (months, mean [SD])	27/9 (6)/91 (40)	32/10 (5)/88 (34)	30/9 (6)/82 (32)
Physical activity: total/once a week/several times a week/once a month (%)	87/20/40/27	92/20/40/32	93/27/40/27
Primary or vocational/secondary/university education (%)	20/40/40	28/28/44	23/40/37
Occupational activity/Blue-collar/white-collar/pink-collar workers (%)	87/20/27/40	88/20/28/40	90/16/37/37
Number of sexual partners (n; mean [SD])	2.5 (1.0)	2.8 (1.1)	3.0 (1.0))
Number of marriages (n; mean [SD])/duration of marriages (months; mean [SD])	1.3 (0.7)/47 (19)	1.2 (0.7)/49 (16)	1.2 (0.6)/45 (15)
Number of deliveries (n; mean [SD])/Number of miscarriages (n; mean [SD])	1.6 (0.8)/0.5 (0.5)	1.5 (0.7)/0.5 (0.4)	1.6 (0.7)/0.4 (0.4)
Stress exposure (%, mean [SD])	80	76	83
Systolic blood pressure (mm Hg; mean [SD])	130 (18)	128 (16)	126 (14)
Diastolic blood pressure (mm Hg; mean [SD])	73 (7)	72 (6)	71 (6)

Abbreviation: SD, standard deviation.
^aWomen with cabergoline-induced hypoprolactinaemia.
^bCabergoline-treated women with prolactin levels within the reference range.
^cCabergoline-naïve women with prolactin levels within the reference range.

Table 2. Biochemical variables in the study population
Variable	Group A^a	Group B^b	Group C^c
Prolactin (ng/mL; mean [SD]) (5.0–25.0)^d
At baseline	3.2 (1.5)*^#	15.1 (5.0)	14.0 (6.0)
After 6 mo	14.3 (5.1)^&	14.9 (5.2)	13.2 (5.8)
Total testosterone (nmol/L; mean [SD]) (0.62–3.12)^d
At baseline	1.23 (0.41)*^#	1.59 (0.35)	1.55 (0.31)
After 6 mo	1.62 (0.48)^&	1.68 (0.40)	1.59 (0.37)
Sex hormone-binding globulin (nmol/L; mean [SD]) (20–140)^d
At baseline	65 (23)	57 (14)	55 (15)
After 6 mo	60 (18)	59 (12)	58 (11)
Free androgen index (%; mean [SD]) (0.3–5.6)^d
At baseline	1.89 (0.43)*^#	2.79 (0.35)	2.82 (0.32)
After 6 mo	2.70 (0.59)^&	2.85 (0.41)	2.74 (0.34)
DHEA-S (μmol/L; mean [SD]) (1.65–9.25)^d
At baseline	4.23 (0.95)	4.78 (0.84)	4.55 (0.74)
After 6 mo	4.60 (1.10)	4.86 (0.92)	4.77 (0.68)
Estradiol (pmol/L; mean [SD]) (65–529)^d
At baseline	128 (59)	140 (38)	134 (46)
After 6 mo	135 (61)	143 (41)	146 (42)
FSH (U/L; mean [SD]) (2.60–10.30)^d
At baseline	4.46 (1.25)	3.95 (0.83)	4.07 (0.78)
After 6 mo	4.23 (1.03)	4.08 (0.91)	3.89 (0.71)
LH (U/L; mean [SD]) (2.40–11.30)^d
At baseline	4.11 (1.32)	3.85 (1.05)	3.68 (0.68)
After 6 mo	4.40 (1.42)	3.71 (0.82)	3.98 (0.73)

Abbreviations: DHEA-S, dehydroepiandrosterone sulphate; FSH, follicle-stimulating hormone; IU, international unit; LH, luteinizing hormone; SD, standard deviation; SHBG, sex hormone-binding globulin.
^aWomen with cabergoline-induced hypoprolactinaemia.
^bCabergoline-treated women with prolactin levels within the reference range.
^cCabergoline-naïve women with prolactin levels within the reference range.
^dReference values for the follicular phase.
*Statistically significant vs group B.
^#Statistically significant vs group C.
^&Statistically significant difference between post-treatment and baseline values within the same group.

Table 3. Female sexual function in the study population
Variable	Group A^a	Group B^b	Group C^c
FSFI score (mean [SD])
At baseline	29.72 (3.61)*^#	32.71 (2.85)	32.59 (2.52)
After 6 mo	32.79 (3.05)^&	32.88 (2.97)	32.52 (2.76)
FSFI score ≤ 26.55 (n [%])
At baseline	4 (27)*^#	3 (12)	3 (10)
After 6 mo	1 (7)^&	2 (8)	3 (10)
Sexual desire (mean [SD])
At baseline	4.12 (0.75)*^#	5.29 (0.71)	5.35 (0.65)
After 6 mo	5.23 (0.70)^&	5.36 (0.68)	5.40 (0.58)
Sexual arousal (mean [SD])
At baseline	4.39 (0.82)*^#	5.50 (0.48)	5.42 (0.61)
After 6 mo	5.50 (0.50)^&	5.54 (0.52)	5.29 (0.69)
Lubrication (mean [SD])
At baseline	5.25 (0.73)	5.43 (0.61)	5.39 (0.68)
After 6 mo	5.51 (0.55)	5.47 (0.58)	5.43 (0.60)
Orgasm (mean [SD])
At baseline	5.32 (0.69)	5.51 (0.52)	5.55 (0.56)
After 6 mo	5.56 (0.48)	5.49 (0.53)	5.42 (0.61)
Sexual satisfaction (mean [SD])
At baseline	5.34 (0.70)	5.52 (0.49)	5.48 (0.55)
After 6 mo	5.50 (0.51)	5.45 (0.51)	5.52 (0.57)
Pain (mean [SD])
At baseline	5.30 (0.75)	5.46 (0.57)	5.40 (0.58)
After 6 mo	5.49 (0.67)	5.57 (0.50)	5.46 (0.52)

Abbreviations: FSFI, Female Sexual Function Index; SD, standard deviation.
^aWomen with cabergoline-induced hypoprolactinaemia.
^bCabergoline-treated women with prolactin levels within the reference range.
^cCabergoline-naïve women with prolactin levels within the reference range.
* Statistically significant vs group B.
^#Statistically significant vs group C.
^&Statistically significant difference between post-treatment and baseline values within the same group.

Table 4. Depressive symptoms in the study population
Variable	Group A^a	Group B^b	Group C^c
BDI-II score (mean [SD])
At baseline	11.8 (4.0)*^#	7.6 (3.2)	6.9 (3.0)
After 6 mo	8.0 (3.5)^&	7.4 (3.8)	7.1 (3.4)
Depressive symptoms (n ([%])
At baseline	6 (47)*^#	2 (8)	3 (10)
After 6 mo	2 (13)^&	2 (8)	3 (10)
Mild symptoms (n [%])
At baseline	6 (47)*^#	2 (8)	3 (10)
After 6 mo	2 (13)^&	2 (8)	2(8)
Moderate symptoms (n [%])
At baseline	0 (0)	0 (0)	0 (0)
After 6 mo	0 (0)	0 (0)	0 (0)
Severe symptoms (n [%])
At baseline	0 (0)	0 (0)	0 (0)
After 6 mo	0 (0)	0 (0)	0 (0)

Abbreviations: BDI-II, Beck Depression Inventory-Second Edition; SD, standard deviation.
^aWomen with cabergoline-induced hypoprolactinaemia.
^bCabergoline-treated women with prolactin levels within the reference range.
^cCabergoline-naïve women with prolactin levels within the reference range.
*Statistically significant vs group B.
^#Statistically significant vs group C.
^&Statistically significant difference between post-treatment and baseline values within the same group.

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Sexual Function and Depressive Symptoms in Young Women With Hypoprolactinemia

Abstract and Introduction

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