ORIGINAL RESEARCH—WOMEN'S SEXUAL HEALTH: Sexual Dysfunction in Women During Dialysis and after Renal Transplantation

Authors


Maria Teresa Filocamo MD, Urology, University of Florence, Viale Pieraccini 18 Florence Italy 50137, Viale Pieraccini 18, Florence, 50137, Italy. Tel: 055417645; Fax: +390554377755; E-mail: mariateresa.filocamo@unifi.it

ABSTRACT

Introduction.  Disorders of the reproductive system and menstrual abnormalities often associated with loss of libido and inability to reach orgasm are common in adults of both sexes with an end-stage renal disease. These symptoms may significantly contribute to depression and reduce the sexual activity of women.

Aim.  To determine if sexual function, as well as hormonal status, improves after kidney transplantation, comparing a group of pre-menopausal women during dialysis and after a successful renal transplantation.

Methods.  We enrolled 58 women that received kidney transplantation. Patients included were 18–45 years old, on hemodialysis for more than 6 months following a fully functioning kidney transplantation, and on a stable corticosteroids immunosuppressive regimen for at least 6 months. All women underwent a general and urogynecological examination, a hormonal profile determination, and filled out the Female Sexual Function Index (FSFI) and a Beck Depression Inventory questionnaire administered during dialysis and 12 months after transplantation.

Main Outcome Measures.  We evaluated the prevalence of Female Sexual Dysfunction according to the FSFI cutoff points, sexual hormonal status, and menstrual status during dialysis and 12 months after kidney transplantation.

Results.  Nineteen out of 58 women left the study prematurely. Thirty-nine women (mean age 36 ± 5.9 years) completed the study. A total of 74% of the patients had menstrual disturbances during dialysis, as opposed to 45% after transplantation (P < 0.001). Sixteen out of 39 (41%) patients acknowledged having an active sexual life during dialysis. Thirty-four out of 39 (88%) transplanted patients acknowledged having an active sexual life (Fischer's exact test P = 0.000039). The hormonal profile and FSFI results improved significantly after transplantation.

Conclusion.  This study demonstrates that a successful transplantation should improve the sexual life in women with chronic renal failure. Filocamo MT, Zanazzi M, Li Marzi V, Lombardi G, Del Popolo G, Mancini G, Salvadori M, and Nicita G. Sexual dysfunction in women during dialysis and after renal transplantation. J Sex Med 2009;6:3125–3131.

Introduction

Disorders of the reproductive system and abnormalities on the hypothalamic-pituitary-gonadal (HPG) axis are common in adults of both sexes with an end-stage renal disease (ESRD). Disturbances in sexual function are a common feature in women with chronic renal failure. Women with ESRD have a higher risk of sexual dysfunction than healthy women [1]. Abnormal menstrual cycles, especially amenorrhea, occur in the majority of pre-menopausal women undergoing long-term dialysis therapy, often associated with loss of libido and inability to reach orgasm [2,3].

Moreover, elevated circulating prolactin levels, because of both decreased metabolic clearance and an increased production, are common. It has been postulated that elevated prolactin levels may contribute to the impairment of hypothalamic-pituitary function and cause galactorrhea in these patients. Furthermore, loss of libido is reported to be one of the principal symptoms in females with hyperprolactinemia [4].

These symptoms may significantly contribute to depression and to the reduction of sexual activity [5].

After a successful kidney transplantation, menses and fertility of the majority of pre-menopausal women were restored, because of the normalization of the hormonal serum profile [6].

As the clinical outcomes of renal transplantation improved in terms of post-operative complications and patient survival, other results became important targets of evaluation. In particular, literature on sexual health, as a part of health-related quality of life for renal transplanted women, is limited.

Aim

The aim of this study is to determine if sexual function, as well as hormonal status, improves after kidney transplantation, comparing a group of pre-menopausal women during dialysis and 1 year after a successful renal transplantation.

Methods

This prospective study was conducted between January 2005 and December 2008. We enrolled 58 women with ESRD that then received kidney transplantation. Inclusion criteria were: women between the ages of 18–45 with ESRD who were in hemodialysis for more than 6 months, followed by a fully functioning kidney transplantation (serum creatinine 0.8–1.3 mg/dL and a glomerular filtrate rate (GFR) > 90 mL/min), and a stable corticosteroids immunosuppressive regimen for at least 6 months. Exclusion criteria were: hysterectomy and/or ovarectomy, history of overactive bladder or chronic pelvic pain, history of prolactinemia or presence of hypophisis adenoma prior to dialysis, and major psychiatric disorders. All women underwent a detailed general and urogynecological exam and a serum hormonal profile determination.

A detailed sexual anamnesis was taken focusing on the presence of sexual activity, eventual sexual dysfunctions, and risk factors for sexuality.

The Female Sexual Function Index (FSFI) and Beck Depression Inventory (BDI) questionnaires were filled out [7,8].

The scores for each instrument were calculated according to the recommended scoring system: a normal score for the FSFI was greater than 26.55 [9]. For the BDI, depression disturbance was indicated with a total score greater than 17. Four subgroups of female sexual dysfunctions (FSD), namely sexual desire disorder, sexual arousal disorder, orgasmic disorder, and sexual pain disorder, were identified. If the correspondent FSFI domain sub-score was less than two-thirds of the maximum score, we assumed that patients had one of the aforementioned FSD [10].

The questionnaires were administered during dialysis when patients were put on the waiting list for transplant and at least 12 months after a successful kidney transplantation. Questionnaires were administered by two different clinicians, by a nephrologist (GM) before transplant, and by a urologist after renal transplantation (MTF). The results were evaluated by two independent clinicians (VLM and GL) blinded to the studied population.

From all patients (menstruating and non-menstruating), serum samples for sexual hormones were taken twice. In particular, for menstruating women, both during dialysis and 12 months after transplantation, serum samples for prolactin, FSH, LH, and 17-beta-oestradiol determinations were taken on the sixth to eighth day of the cycle, and progesterone and testosterone concentration 4–6 days before anticipated menses. In non-menstruating women, both during dialysis and at least 12 months after transplantation, serum sex hormone concentrations were measured once in the same day. The menstrual cycles lasting 28–32 days were classified as normal, shorter ones as polymenorrhea and longer ones as oligomenorrhea. Absence of menses for at least 6 months was diagnosed as amenorrhea. Satisfactory renal function was determined by serum creatinine levels and GFR.

Women's sexuality post-transplant was considered enhanced if at least one of the following occurred: an increase of 60% or more for each FSFI domain, or a global improvement if the FSFI total score was 60% or more over baseline, as reported by other authors [10].

Informed consent was obtained from all of the patients and the design of the study was in accordance with the Declaration of Helsinki.

Statistical Analysis

The results of the hormonal determination and the FSFI total score pre- and post-transplantation were analyzed with the paired Wilcoxon test. The number of patients with an active sexual life during dialysis therapy and after renal transplantation was analyzed with Fisher's exact test. The univariate correlation between the hormonal profile and the FSFI total score, as well as between the BDI and the FSFI total score, was tested with Spearman's correlation coefficient. Moreover, a multivariate logistic model to analyze the independent influence on the FSFI total score, including significant parameters from univariate analysis (P < 0.05), was conducted by using multivariate linear regression analysis. Statistical significance was indicated by a two-tailed P < 0.05. Statistical analysis was performed with SPSS version 17.0 (SPSS Inc., Chicago, IL, USA).

Main Outcome Measures

  • 1) FSFI results during dialysis and after a successful kidney transplantation.
  • 2) Serum hormonal profile during dialysis and after a successful kidney transplantation.
  • 3) Menstrual status during dialysis and after a successful kidney transplantation.

Results

Ten out of 58 transplanted patients were removed from the study because of unsatisfactory allograft stable functioning (creatinine levels > 1.5 mg/dL and/or GFR < 90 mL/min). Seven out of the remaining 48 patients were removed because of acute rejection episodes during the post-transplant period requiring methylprednisolone therapy. Two patients left the study prematurely because of allograft nephrectomy because of vascular rejection. Overall, 39 patients (mean age 36 ± 5.9 years) completed the study protocol, all of whom were in a stable heterosexual relationship.

The mean length of dialysis was 18 months (range 12–36), and the mean time after transplantation was 16 months (range 13–46). Subject characteristics are summarized in Table 1.

Table 1.  Subject characteristics
 During dialysis1 year after transplantation
N° of patients3939
Body mass index (BMI)22.1 ± 3.6725.7 ± 3.16
Educational Level  
 Middle school or less88
 High School2424
 College77
Etiology of ESRD  
 Glomerulonephritis2121
 Diabetic nephropathy33
Polycistic kidney disease55
 Nephroangiosclerosis33
 Unspecified77
Medications  
 Beta-blockers910
 ACE98
 Alfa-blockers109
Calcium channel blockers1822
 Diuretics02
 EPO340
 Prednisolone039
 Cyclosporine034
Micophenolate mophetil029
 FK-50605

Prior to transplant, 15 out of 39 patients (39%) had amenorrhea, 12 oligomenorrhea, 2 polimenorrhea, and only 10 out of 39 had eumenorrhea. Following transplant, however, 21 out of 39 patients (54%) had eumenorrhea, and 18 (45%) patients had menstrual disturbances: 6 (15%) had amenorrhea, 9 (23%) had oligomenorrhea, and 3 patients (8%) had polymenorrhoea, with a statistically significant difference during dialysis and after transplantation (P < 0.001). Menstrual cycle characteristics during the two analyzed periods are shown in Table 2. The hormonal status of patients in dialysis and after transplantation is shown in Table 3.

Table 2.  Menstrual status during dialysis and 12 months after renal transplantation
 During dialysis (39 patients)12 months after transplant (39 patients)
Amenorrhea156
Oligomenorrhea129
Polimenorrhea23
Eumenorrhea1021
Table 3.  Hormonal status in menstruating and non-menstruating patients during dialysis and 12 months after renal transplantation
Menstruating patients
 During dialysis1 year after transplantationP
FSH5.99 ± 3.876.30 ± 2.70ns
LH9.09 ± 6.476.03 ± 2.60ns
Prolactin436 ± 211278 ± 90.7<0.01
17β– stradiol64.8 ± 30.059.2 ± 18.5ns
Testosterone0.35 ± 0.270.44 ± 0.22ns
Progesterone25.7 ± 23.251.6 ± 22.3<0.05
Non-menstruating Patients
 During dialysis1 year after transplantationP
FSH33.2 ± 53.515.42 ± 3.70<0.01
LH21.7 ± 31.913.9 ± 9.60<0.01
Prolactin1,704 ± 1,610739 ± 432<0.001
17β– estradiol18.6 ± 20.734.8 ± 32<0.001
Testosterone0.20 ± 0.220.34 ± 0.62<0.05
Progesterone11.0 ± 10.112.0 ± 9.8ns

Sixteen out of 39 (41%) patients acknowledged having an active sexual life before transplant, as opposed to 34 out of 39 (88%) after transplantation (Fischer's exact test P = 0.000039). Twenty-three out of 39 reported an absence of sexual activity before transplantation, 15 because of dialysis and the remaining 8 for other reasons. Five out of 39 transplanted patients confirmed an absence of sexual activity because of the presence of the allograft.

Sexual dysfunction was diagnosed in 10 out of 16 patients with an active sexual life before transplant, and in 11 out of 34 patients with an active sexual life after transplantation, with a significant difference between the groups (Fischer's exact test P = 0.05). FSFI results pre-and post-transplant were available for only 16 patients with an active sexual life before and after transplantation. We observed an improvement in the FSFI total score and in all domain sub-scores (Figure 1, paired Wilcoxon test P < 0.002). We also separately analyzed the questionnaires (pre- and post-transplant) of the 10 patients with FSD during dialysis and found a statistical significant improvement in total scores and in all domain sub-scores (Figure 2, paired Wilcoxon test P = 0.002). Female sexual disorders pre- and post-transplantation are summarized in Table 4.

Figure 1.

Results of FSFI questionnaire in 16 patients with an active sexual life both during dialysis and after transplant.

Figure 2.

Results of FSFI questionnaire in 10 patients with FSD during dialysis and the same patients after transplant.

Table 4.  FSD distribution during dialysis and 12 months after renal transplantation
 10 pts with FSD during dialysis11 pts with FSD after transplantation
Desire76
Arousal107
Orgasm94
Pain73

The mean score of the BDI questionnaire was 7 (range 6–11) and 11 (range 7–19) in transplanted and dialysis patients, respectively, with a statistically relevant difference (Wilcoxon test P = 0.01). We did not find a univariate correlation between the BDI and FSFI total scores pre- and post-transplantation (Spearman's coefficient of rank correlation P = 0.29).

The hormonal profile, the menstrual status, and the FSFI total scores had a significant statistical correlation (Spearman's correlation coefficient was always P < 0.05).

After adjustment for multiple testing, only prolactin and menstrual status remained significantly correlated with the FSFI total score as independent variables.

Discussion

Our study reports the positive effects of kidney transplantation on female sexual function, as well as on menstrual and hormonal status in a group of pre-menopausal women when a good graft function is present.

Few areas of human behavior are as complex as sexuality. Sexual function is very sensitive to illness, psychological distress, and bad interpersonal relationships. Chronic illness is largely associated with diminished sexual activity because of malaise, fatigue, and changes in body image. It is difficult to define “normal” sexual function or frequency of sexual activities because of the wide variation in sexual practices between different cultural groups and ethnicities [11]. Key to clinical assessment is a detailed sexual, medical, and psychosocial history [12]. Data about the concurrence of FSD with many medical disorders are scarce; in particular, we know little about the recovery of sexual activity after renal transplantation, especially in female patients. There are relatively few studies in literature investigating sexual dysfunction in renal transplanted patients, and among these, very few included women. Moreover, different methodological approaches were used for these studies; in fact, well-validated questionnaires about FSD, tested in a range of languages, have only recently become available. In addition, many studies include only patients who are sexually active, and exclude those for whom medical and/or psychological factors have precluded any sexual relationship.

The inclusion of non-sexually active women in the statistical analysis and the exclusion of women with either a bad graft function or an instable corticosteroids therapy are exclusive characteristics of this study.

Only one article in literature by Tauchmanova et al. takes into consideration the functioning of the graft and the hormonal status after kidney transplantation, but in this study sexual function was not investigated with validated tools [5]. The authors reported menstrual disturbances in 50% of their patients even after kidney transplantation, mainly amenorrhea [5].

In our study, 44% of patients presented menstrual disturbances 12 months after a successful kidney transplantation, significantly lower with respect to women on dialysis. In some cases menstrual disturbances persist after transplantation despite a significant improvement in hormonal status. The sexual endocrine pattern during dialysis includes generally elevated serum concentrations of gonadotropins and prolactin and a depression of circulating estradiol. After successful renal transplantation, we observed an improvement of hormonal status with a reduction of gonadotropin and an elevation of the circulating estradiol level. The prolactin levels decreased significantly in the majority of our patients as well, although the mean remained above the normal range. It has been postulated that the permanence of the HPG axis alteration, despite the normalization of hormonal status could be influenced prevalently by immunosuppressive treatments and other medications such as corticosteroids and beta-blockers [5].

Several pharmaco-therapies can increase the risk of FSD, and many of these drugs are used in the treatment of renal transplant recipients such as gluco-corticoids, calcineurine inhibitors, azathioprine, mycophenolate mofetile, rapamicime, anti-hypertensive medications, lipid-lowering agents, and histamine H2-receptor blockers [6,13,14]. The effect of some of these drugs and their interactions on genital and sexual function are still unclear. It is difficult to separate the drug effects from the underlying medical condition. Moreover, some medications are utilized both in transplanted and dialysis patients. To date, the correlations between the effects of immunosuppressive drugs and sexual function are not well understood. It could be an area of potential future studies.

The improvement in hormonal status and the restoration of menses positively influenced the sexual function of these women. The rate of women who declared having an active sexual life is significantly higher after transplantation (46% vs. 88%), and only 32% of women with an active sexual life after transplantation complained of an FSD, compared to 62% during dialysis.

If we consider the absence of sexual activity an FSD, the overall rate of sexual disorder in our study was 85% during dialysis vs. 35% after transplantation.

Other studies that included female patients have reported a wide percentage of sexual dysfunction after renal transplantation that range between 44% to 94%, but none of these studies take into consideration the graft function and the hormonal status of the patients [15–17].

In their comparison of female and male patients, Ozdemir et al. justify the higher sexual dysfunction rate in female patients with the lower level of education and higher level of depression [16]. In another recent study, Tavallaii et al. demonstrate how intercourse frequency is correlated to mental health in females, and intercourse satisfaction is correlated to physical health in male kidney transplant recipients [18]. Many studies have previously demonstrated that serum creatinine level is the major biochemical variable affecting FSFI scores both during dialysis and after renal transplantation [14].

Though we did not compare women with men, we decided to exclude the patients with bad or suboptimal graft function in order to reduce the bias derived by the alteration of creatinine levels and/or changes in immunosuppressive therapy. We found a significant difference in the BDI score before and after transplantation, although in both groups the BDI scores were not significant for clinical depression (major psychiatric disorders were excluded a priori). No correlation was found between the BDI and FSFI scores. The results of multivariate analysis indicated that the prolactin level and menstrual status are the two variables that independently influenced the FSFI final score.

Desire disorders and arousal disorders were equally present before and after transplantation. Other authors have already described a reduction in vaginal congestion in women on dialysis that can persist after renal transplantation, despite improved subjective arousal, which is probably caused by chronic damage because of hypertension or diabetes [19].

Orgasmic disorder is the most represented dysfunction in dialysis. Other studies have reported the high incidence of orgasmic disorders in patients with hyperprolactinemia [4].

Hyperprolactinemia and hypothalamic-pituitary axis abnormalities associated with low estrogenism cause pallor, dryness, increased fragility, and thinning of vulvovaginal epithelium with introital pain and post-coital burning. Vaginal moisture returns and pain during intercourse is reduced once hormonal status is restored after renal transplant [20]. The major limits of this study are the small sample size, the lack of a psychometric tool to investigate women's sexual distress, and the lack of any investigation into immunosuppressive therapy.

Though data showed an amelioration in women's sexual life after a successful renal transplantation, monitoring this aspect is required and, when needed, a sexual assessment should be integrated into the routine examination of female recipients.

Conclusions

This study demonstrates with validated tools that a successful kidney transplantation should improve the sexual life, as well as hormonal status, in women with chronic renal failure.

Conflict of Interest: None.

Statement of Authorship

Category 1

  • (a)Conception and DesignMaria Teresa Filocamo; Maria Zanazzi
  • (b)Acquisition of DataGiovanni Mancini; Maria Zanazzi; Maria Teresa Filocamo
  • (c)Analysis and Interpretation of DataVincenzo Li Marzi; Giuseppe Lombardi

Category 2

  • (a)Drafting the ArticleMaria Teresa Filocamo; Vincenzo Li Marzi; Giulio Del Popolo
  • (b)Revising It for Intellectual ContentGiulio Nicita; Maurizio Salvadori

Category 3

  • (a)Final Approval of the Completed ArticleMaria Teresa Filocamo; Maria Zanazzi; Vincenzo Li Marzi; Giovanni Mancini; Giuseppe Lombardi; Giulio Del Popolo; Maurizio Salvadori; Giulio Nicita

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