Sexual Function in Chronic Kidney Disease
2007; Elsevier BV; Volume: 14; Issue: 2 Linguagem: Inglês
10.1053/j.ackd.2007.01.002
ISSN1548-5609
AutoresPriya Anantharaman, Rebecca J. Schmidt,
Tópico(s)Reproductive Health and Contraception
ResumoEndocrine abnormalities are common in patients with chronic kidney disease (CKD) and lead to sexual dysfunction, anemia, hyperparathyroidism, and altered mineral metabolism. Common clinical problems include disturbances in menstruation in women, erectile dysfunction in men, and decreased libido and infertility in both sexes. Organic factors tend to be prominent and are related to uremia and other comorbid illnesses. Psychological factors and depression may exacerbate the primary problem. Alterations in the hypothalamic-pituitary axis are seen early in CKD and tend to worsen after patients start dialysis. Hypogonadism plays a dominant role in male sexual function, whereas changes in hypothalamic-pituitary function predominate in female sexual dysfunction. In patients on dialysis, treatment strategies include optimizing dose of dialysis, correction of anemia with erythropoietin, and correction of hyperparathyroidism. Successful kidney transplantation may restore normal sexual function, especially in younger patients. Endocrine abnormalities are common in patients with chronic kidney disease (CKD) and lead to sexual dysfunction, anemia, hyperparathyroidism, and altered mineral metabolism. Common clinical problems include disturbances in menstruation in women, erectile dysfunction in men, and decreased libido and infertility in both sexes. Organic factors tend to be prominent and are related to uremia and other comorbid illnesses. Psychological factors and depression may exacerbate the primary problem. Alterations in the hypothalamic-pituitary axis are seen early in CKD and tend to worsen after patients start dialysis. Hypogonadism plays a dominant role in male sexual function, whereas changes in hypothalamic-pituitary function predominate in female sexual dysfunction. In patients on dialysis, treatment strategies include optimizing dose of dialysis, correction of anemia with erythropoietin, and correction of hyperparathyroidism. Successful kidney transplantation may restore normal sexual function, especially in younger patients. A myriad of sexual problems affect men and women with chronic kidney disease (CKD), including decreased libido, erectile dysfunction, dysmenorrheal, and infertility. Hormonal changes are seen in prolactin, gonadotropins, and gonadal hormones. Hormonal alterations along with vascular, neurologic, psychogenic, and other factors, such as medications, contribute to the development of sexual dysfunction.1Palmer B.F. Sexual dysfunction in uremia.J Am Soc Nephrol. 1999; 10: 1381-1388PubMed Google Scholar In women, elevated levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are common.2Holley J.L. Schmidt R.J. Bender F. et al.Gynecologic and reproductive issues in women on dialysis.Am J Kidney Dis. 1997; 29: 685-690Abstract Full Text PDF PubMed Scopus (189) Google Scholar, 3Chryssicopoulos A. Koutsikos D. Kapetanski A. et al.Evaluation of the hypothalamic-pituitary axis in uremic males using dynamic tests: the possible role of testicular inhibin: A preliminary report.Ren Fail. 1996; 19: 911-921Crossref Scopus (11) Google Scholar, 4Handelsman D.J. Dong Q. Hypothalamic-pituitary gonadal axis in chronic renal failure.Endocrinol Metab Clin North Am. 1993; 22: 145-161PubMed Google Scholar Women with end-stage renal disease (ESRD) are usually amenorrheic or have irregular menstrual cycles.5Lim V.S. Henriquez C. Dieversten G. et al.Ovarian function in chronic renal failure Evidence of hypothalamic anovulation.Ann Intern Med. 1980; 93: 21-27Crossref PubMed Scopus (187) Google Scholar The frequency of menstruation in women of childbearing age with ESRD is variable, between 8% and 10%,6Perez R.J. Lipner H. Abdulla N. et al.Menstrual dysfunction of patients undergoing hemodialysis.Obstet Gynecol. 1978; 51: 552-555Crossref PubMed Scopus (26) Google Scholar, 7Schmidt R.J. Holley J.L. Fertility and contraception in end stage renal disease.Adv Ren Replace Ther. 1998; 5: 38-44PubMed Google Scholar and anovulatory cycles occur commonly.7Schmidt R.J. Holley J.L. Fertility and contraception in end stage renal disease.Adv Ren Replace Ther. 1998; 5: 38-44PubMed Google Scholar In contrast to women with ESRD, premenopausal women with normal kidney function have both tonic and cyclic components of gonadotropin secretion. The tonic component is regulated through basal gonadotropin secretion and the cyclic component through the midcycle surge of LH and its effects on the hypothalamus. Ovarian dysfunction in women on dialysis is characterized by the absence of cyclic gonadotropin and estradiol release, which results in the lack of progestational changes in the endometrium.5Lim V.S. Henriquez C. Dieversten G. et al.Ovarian function in chronic renal failure Evidence of hypothalamic anovulation.Ann Intern Med. 1980; 93: 21-27Crossref PubMed Scopus (187) Google Scholar Midcycle LH surge cannot be mitigated with endogenous administration of estrogen, confirming a central hypothalamic derangement.5Lim V.S. Henriquez C. Dieversten G. et al.Ovarian function in chronic renal failure Evidence of hypothalamic anovulation.Ann Intern Med. 1980; 93: 21-27Crossref PubMed Scopus (187) Google Scholar, 8Leavey S.F. Weitzel W.F. Endocrine abnormalities in chronic renal failure.Endocrinol Metab Clin North Am. 2002; 31: 107-119Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar Pregnancy is uncommon in women on dialysis, and successful conception in dialysis patients is rare.9Holley J.L. Reddy S.S. Pregnancy in dialysis patients: A review of outcomes, complications, and management.Semin Dial. 2003; 16: 384-388Crossref PubMed Scopus (121) Google Scholar, 10Okundaye I. Abrinko P. Hou S. Registry of pregnancy in dialysis patients.Am J Kidney Dis. 1998; 31: 766-773Abstract Full Text PDF PubMed Scopus (247) Google Scholar Pregnancy is more common in kidney transplant recipients and in women with chronic kidney disease. Fertility rates in patients with ESRD are extremely low and difficult to quantify.9Holley J.L. Reddy S.S. Pregnancy in dialysis patients: A review of outcomes, complications, and management.Semin Dial. 2003; 16: 384-388Crossref PubMed Scopus (121) Google Scholar Pregnancy is more common in women with reduced kidney function, although CKD is also associated with infertility.11Sturgiss S.N. Davidson J.M. Effect of pregnancy on long-term function of renal allografts.Am J Kidney Dis. 1992; 19: 167-172PubMed Scopus (77) Google Scholar Menopause tends to occur earlier in women on dialysis.12Holley J.L. Schmidt R.J. Bender F. et al.Gynecologic and reproductive issues in women on dialysis.Am J Kidney Dis. 1997; 29: 685-690Abstract Full Text PDF PubMed Google Scholar Accurate estimates of fertility rates for men on dialysis are not well known. Men with CKD suffer from low levels of free and total testosterone.1Palmer B.F. Sexual dysfunction in uremia.J Am Soc Nephrol. 1999; 10: 1381-1388PubMed Google Scholar, 8Leavey S.F. Weitzel W.F. Endocrine abnormalities in chronic renal failure.Endocrinol Metab Clin North Am. 2002; 31: 107-119Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar Approximately two thirds of men on dialysis have low serum testosterone levels. This may occur as a result of an inhibitory factor in uremic serum, which inhibits LH signaling at the level of the Leydig cells. Stimulation of testosterone release by administration of human chorionic gonadotropin results in a blunted response in uremic men.13Stewart-Bentley M. Gans D. Horton R. Regulation of gonadal function in uremia.Metabolism. 1974; 23: 1065-1072Abstract Full Text PDF PubMed Scopus (84) Google Scholar Changes in the pulsatile release of gonadotropin-releasing hormone and LH and reduced feedback inhibition of LH production (because of low levels of testosterone) contribute to high-serum LH levels.14Palmer B.F. Outcomes associated with hypogonadism in men with chronic kidney disease.Adv Chronic Kidney Dis. 2004; 11: 342-347Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar Decreased LH metabolism caused by kidney disease is a factor, and estrogen levels are also elevated in men with advanced kidney disease. FSH secretion is increased but to a lesser degree than LH so that the LH/FSH ratio increases. Feedback inhibition of FSH is impaired because of decrease in the peptide inhibin, which is produced by Sertoli cells.14Palmer B.F. Outcomes associated with hypogonadism in men with chronic kidney disease.Adv Chronic Kidney Dis. 2004; 11: 342-347Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar These hormonal changes are detected in the early stages of kidney disease and progressively worsen as kidney disease progresses,8Leavey S.F. Weitzel W.F. Endocrine abnormalities in chronic renal failure.Endocrinol Metab Clin North Am. 2002; 31: 107-119Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar particularly after initiation of dialysis. A successful kidney transplant restores balance in the hypothalamic-pituitary axis with restoration of pulsatile GnRH and LH release.14Palmer B.F. Outcomes associated with hypogonadism in men with chronic kidney disease.Adv Chronic Kidney Dis. 2004; 11: 342-347Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar Recovery of spermatogenesis depends on the extent of injury to the seminiferous tubules. Men with high FSH levels tend to have a poorer prognosis for improvement of sperm counts.14Palmer B.F. Outcomes associated with hypogonadism in men with chronic kidney disease.Adv Chronic Kidney Dis. 2004; 11: 342-347Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar Spermatogenesis and sperm motility are affected and oligo- or azoospermia are common and lead to male infertility. Prolactin levels are elevated in both men and women on dialysis because of increased production and reduced renal clearance. Strikingly high numbers of women on hemodialysis (70%-90%) and most peritoneal dialysis patients have hyperprolactinemia.15Lim V. Kathpalia S.C. Frohman L.A. Hyperprolactinemia and impaired pituitary response to suppression and stimulation in chronic renal failure: Reversal after transplantation.J Clin Endocrinol Metab. 1979; 48: 101-107Crossref PubMed Scopus (122) Google Scholar, 16Hou S.H. Grossman S. Molitch M.E. Hyperprolactinemia in patients with renal insufficiency and chronic renal failure requiring hemodialysis or continuous ambulatory peritoneal dialysis.Am J Kidney Dis. 1985; 6: 245-249PubMed Scopus (95) Google Scholar Secondary hyperparathyroidism may contribute to hyperprolactinemia.8Leavey S.F. Weitzel W.F. Endocrine abnormalities in chronic renal failure.Endocrinol Metab Clin North Am. 2002; 31: 107-119Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar Women with CKD tend to experience premature menopause, on average 4.5 years ahead of their healthy counterparts.17Weisinger J.R. Bellorin-Font E. Outcomes associated with hypogonadism in women with chronic kidney disease.Adv Chronic Kidney Dis. 2004; 11: 361-370Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar, 18Gipson D. Katz L.A. Stehman-Breen C. Principles of dialysis: Special issues in women.Semin Nephrol. 1999; 19: 140-147PubMed Google Scholar Thus, most women with CKD are postmenopausal. Short-term effects of hypogonadism in women include skin wrinkling, urinary incontinence, hypoactive sexual functions, hot flashes, sleep disorders, and depression. Long-term effects include osteoporosis, disorders of cognitive function, and cardiovascular disease.17Weisinger J.R. Bellorin-Font E. Outcomes associated with hypogonadism in women with chronic kidney disease.Adv Chronic Kidney Dis. 2004; 11: 361-370Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar Most women with CKD report decreased libido consistent with sexual aversion disorder or hypoactive sexual desire disorder (HSDD) as well as the inability to achieve an orgasm.17Weisinger J.R. Bellorin-Font E. Outcomes associated with hypogonadism in women with chronic kidney disease.Adv Chronic Kidney Dis. 2004; 11: 361-370Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar, 19Toorians A.W. Janssen E. Laan E. et al.Chronic renal failure and sexual functioning: Clinical status versus objectively assessed sexual response.Nephrol Dial Transplant. 1997; 12: 2654-2663Crossref PubMed Scopus (147) Google Scholar Hypoactive sexual desire disorder is defined as a persistent absence of sexual thoughts and or desire for and receptivity to sexual activity that causes personal distress.20Nappi R.E. Wawra L. Schmitt S. Hypoactive sexual desire disorder in postmenopausal women.Gynecol Endocrinol. 2006; 22: 318-323Crossref PubMed Scopus (32) Google Scholar Endocrine abnormalities in women with CKD, particularly decreased production of estrogen, lead to vaginal dryness and dyspareunia, which may contribute to reduced sexual function.17Weisinger J.R. Bellorin-Font E. Outcomes associated with hypogonadism in women with chronic kidney disease.Adv Chronic Kidney Dis. 2004; 11: 361-370Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar Up to 65% of women on hemodialysis report problems with sexual function, and up to 40% no longer engage in sexual intercourse.21Milde F.K. Hart L.K. Fearing M.O. Sexuality and fertility concerns of dialysis patients.ANNA J. 1996; 23: 307-313PubMed Google Scholar Thus, although infertility among women with renal disease is primarily the result of abnormalities in endocrinologic function leading to anovulation, lack of sexual activity may also contribute to the low rates of pregnancy in these women. Hypogonadism and low testosterone levels are the norm in men with CKD. Hypogonadism causes alterations in the hypothalamic pituitary gonadal.16Hou S.H. Grossman S. Molitch M.E. Hyperprolactinemia in patients with renal insufficiency and chronic renal failure requiring hemodialysis or continuous ambulatory peritoneal dialysis.Am J Kidney Dis. 1985; 6: 245-249PubMed Scopus (95) Google Scholar Low levels of testosterone in men can contribute to decreased libido, erectile dysfunction, oligospermia and infertility, decrease in muscle mass, osteopenia and osteoporosis, and anemia. The prevalence of erectile dysfunction (ED) may be as high as 70% to 80% in men with CKD and is similar to rates reported in men with ESRD.16Hou S.H. Grossman S. Molitch M.E. Hyperprolactinemia in patients with renal insufficiency and chronic renal failure requiring hemodialysis or continuous ambulatory peritoneal dialysis.Am J Kidney Dis. 1985; 6: 245-249PubMed Scopus (95) Google Scholar Endocrine abnormalities, especially low levels of testosterone and hyperprolactinemia, diminish libido and thereby contribute to ED. Decline in libido and ED contribute to decreased frequency of sexual intercourse. Comorbid illnesses commonly associated with CKD also lead to ED; risk factors for the development of ED in CKD patients are similar to cardiovascular risk factors including increasing age, diabetes, hypertension, dyslipidemia, and smoking. Psychological problems and anxiety are major contributing factors as well. Few studies address decreased libido and sexual function in women with CKD. Quality of life surveys suggest that discussion of sexual function and other reproductive issues are a key component of psychosocial assessment and that education on sexual function in the setting of CKD is widely needed.19Toorians A.W. Janssen E. Laan E. et al.Chronic renal failure and sexual functioning: Clinical status versus objectively assessed sexual response.Nephrol Dial Transplant. 1997; 12: 2654-2663Crossref PubMed Scopus (147) Google Scholar, 22Raiz L. Davies E.A. Ferguson R.M. Sexual functioning following renal transplantation.Health Soc Work. 2003; 28: 264-272Crossref PubMed Scopus (42) Google Scholar Pharmacologic therapy with estrogen/progesterone and androgens along with correction of anemia, ensuring adequate dialysis delivery, and treatment of underlying depression are important. Changes in lifestyle such as smoking cessation, strength training, and aerobic exercises may decrease depression, enhance body image, and have positive impacts on sexuality. Women with CKD who suffer from chronic anovulation and lack of progesterone secretion may be treated with oral progesterone at the end of each menstrual cycle to restore menstrual cycles. It is not clear whether unopposed estrogen stimulation of the endometrium (due to anovulatory cycles) predisposes women with CKD to endometrial hyperplasia or endometrial cancer. Routine gynecologic follow-up is recommended in these cases, and some women may also benefit from the use of a progestational agent several times a year to mitigate the effects of estrogen on the endometrium. Low estradiol levels in amenorrheic women on dialysis leads to vaginal atrophy and dyspareunia. Topical estrogen cream and vaginal lubricants may be helpful in this situation. Women with ESRD who do have menstrual cycles should be encouraged to use contraception; because of poor pregnancy outcomes, restoring fertility is not an advisable therapeutic goal. Transdermal hormone replacement therapy (HRT) allows sustained physiological serum estradiol concentrations in premenopausal women with estrogen deficiency on hemodialysis, with the restoration of regular menses and a marked improvement in sexual function.23Matuszkiewicz-Rowinska J. Skorzewska K. Radowicki S. et al.The benefits of hormone replacement therapy in pre-menopausal women with oestrogen deficiency on haemodialysis.Nephrol Dial Transplant. 1999; 14: 1238-1242Crossref PubMed Scopus (67) Google Scholar HRT with estrogens may positively affect sexual desire and may prevent loss of bone mass in postmenopausal women with ESRD.23Matuszkiewicz-Rowinska J. Skorzewska K. Radowicki S. et al.The benefits of hormone replacement therapy in pre-menopausal women with oestrogen deficiency on haemodialysis.Nephrol Dial Transplant. 1999; 14: 1238-1242Crossref PubMed Scopus (67) Google Scholar, 24Holley J.L. Schmidt R.J. Hormone replacement therapy in postmenopausal women with end stage renal disease: A review of the issues.Semin Dial. 2001; 14: 146-149Crossref PubMed Scopus (21) Google Scholar However, as in women with normal kidney function, there remains concern about increased risk of coronary artery disease and strokes in postmenopausal women on HRT. Treatment of decreased libido in women may be challenging, and coincident psychogenic factors such as depression warrant concomitant therapy. Hypoactive sexual desire disorder is the most common sexual problem reported by women with CKD. Testosterone replacement therapy to treat HSDD has been effective in some women without CKD.25Davis S.R. van der Mooren M.J. van Lunsen R.H. et al.Efficacy and safety of testosterone patch for the treatment of hypoactive sexual desire disorder in surgically menopausal women: A randomized, placebo-controlled trial.Menopause. 2006; 13: 387-396Crossref PubMed Scopus (225) Google Scholar, 26Simon J. Braunstein G. Nachtigall L. et al.Testosterone patch increases sexual activity and desire in surgically menopausal wimen with hypoactive sexual desire disorder.J Clin Endocrinol Metab. 2005; 90: 5226-5233Crossref PubMed Scopus (386) Google Scholar However, long-term safety data on the use of androgens in women with CKD and ESRD are very limited. The main adverse effects of testosterone are on lipid profiles, mainly lowering of high-density cholesterol; hepatotoxicity is also possible. Sildenafil citrate has been used to treat postmenopausal women with female sexual arousal disorder. In women with CKD, sildenafil treatment was successful in women with female sexual arousal disorder without concomitant HSDD; no significant improvements were observed in women with both disorders.27Berman J.R. Berman L.A. Toler S.M. et al.Safety and efficacy of sidenafil citrate for the treatment of female sexual arousal disorder: a double-blind, placebo controlled study.J Urol. 2003; 170: 2333-2338Abstract Full Text Full Text PDF PubMed Scopus (195) Google Scholar Bromocriptine may be used in patients with sexual dysfunction and high prolactin levels. However, it is poorly tolerated because of side effects. Other dopaminergic agonists such as lisuride may be better tolerated, but long-term data remain sparse.28Palmer B.F. Sexual dysfunction in men and women with chronic kidney disease and end-stage renal disease.Adv Ren Replace Ther. 2003; 10: 48-60Abstract Full Text PDF PubMed Scopus (124) Google Scholar Correction of secondary hyperparathyroidism with calcitriol may lower prolactin levels, which may be helpful in treating sexual dysfunction.8Leavey S.F. Weitzel W.F. Endocrine abnormalities in chronic renal failure.Endocrinol Metab Clin North Am. 2002; 31: 107-119Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar Treatment with recombinant human erythropoietin (rHuEPO) improves physical and sexual function as well as health-related quality of life in men and women with ESRD.29de Francisco A.L. Fernandez Fresnedo G. Rodrigo E. Past, present and future of erythropoietin use in the elderly.Int Urol Nephrol. 2002; 33: 187-193Crossref PubMed Scopus (9) Google Scholar Several studies have shown improvement in sexual function after rHuEPO use. Correction of anemia, improved sense of well-being, and direct endocrine effects seem to play a role.28Palmer B.F. Sexual dysfunction in men and women with chronic kidney disease and end-stage renal disease.Adv Ren Replace Ther. 2003; 10: 48-60Abstract Full Text PDF PubMed Scopus (124) Google Scholar There is some evidence that rHuEPO therapy may normalize the pituitary gonadal axis, lowering FSH, LH levels, and prolactin and raising serum testosterone.28Palmer B.F. Sexual dysfunction in men and women with chronic kidney disease and end-stage renal disease.Adv Ren Replace Ther. 2003; 10: 48-60Abstract Full Text PDF PubMed Scopus (124) Google Scholar, 30Kokot F. Wicek A. Schmidt-Gayk H. et al.Function of endocrine organs in hemodialysis patients of long term erythropoietin therapy.Artif Organs. 1995; 19: 428-435Crossref PubMed Scopus (52) Google Scholar, 31Schaefer F. van Kaick B. Veldhuis J.D. et al.Changes in the kinetics and biopotency of lutinizing hormone in hemodialyzed men during treatment with recombinant human erythropoietin.J Am Soc Nephrol. 1994; 5: 1208-1215PubMed Google Scholar Guidelines for the use of rHuEPO are currently dictated by the level of hemoglobin with any benefit in sexual function being salutary. Testosterone replacement may also be used to treat anemia, muscle wasting, and bone disease in both men and women in the absence of overt hypogonadism. Androgens were used in the treatment of anemia related to CKD before the availability of rHuEPO. There is a renewed interest in androgens as adjunctive therapy to rHuEPO. Weekly intramuscular nandrolone injections have been given with some success in patients with ESRD.32Johansen K.L. Treatment of hypogonadism in men with chronic kidney disease.Adv Chronic Kidney Dis. 2004; 4: 348-356Abstract Full Text Full Text PDF Scopus (27) Google Scholar Preliminary evidence suggests that nandrolone has anabolic effects in patients with ESRD, including weight gain, increase in serum creatinine, and muscle mass.32Johansen K.L. Treatment of hypogonadism in men with chronic kidney disease.Adv Chronic Kidney Dis. 2004; 4: 348-356Abstract Full Text Full Text PDF Scopus (27) Google Scholar The lack of secondary sexual characteristics and the presence of small soft testicles on physical examination suggest hypogonadism as a cause of impotence.28Palmer B.F. Sexual dysfunction in men and women with chronic kidney disease and end-stage renal disease.Adv Ren Replace Ther. 2003; 10: 48-60Abstract Full Text PDF PubMed Scopus (124) Google Scholar The presence of peripheral or cardiovascular disease may implicate a vascular cause as the etiology for ED, peripheral neuropathy, or a neurogenic bladder, a neurogenic etiology for impotence. Antihypertensive medications, particularly centrally acting agents such as clonidine, beta-blockers, and alpha-blockers, are commonly implicated in ED. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have a lower incidence of impotence. Other drugs commonly implicated in ED include cimetidine, tricyclic antidepressants, phenothiazines, and metoclopramide.28Palmer B.F. Sexual dysfunction in men and women with chronic kidney disease and end-stage renal disease.Adv Ren Replace Ther. 2003; 10: 48-60Abstract Full Text PDF PubMed Scopus (124) Google Scholar Psychological factors may also play a role in the pathophysiology of ED. Nocturnal penile tumescence testing may be used to differentiate organic and psychologic causes of impotence. A patient with normal nocturnal erections during rapid eye movement sleep may benefit from psychological testing and evaluation.28Palmer B.F. Sexual dysfunction in men and women with chronic kidney disease and end-stage renal disease.Adv Ren Replace Ther. 2003; 10: 48-60Abstract Full Text PDF PubMed Scopus (124) Google Scholar The measurement of penile blood flow and blood pressure by Doppler may be helpful to document a vascular etiology of ED. Neurogenic impotence is characterized by prolonged latency time of the bulbocavernous reflex or by the presence of a neurogenic bladder.28Palmer B.F. Sexual dysfunction in men and women with chronic kidney disease and end-stage renal disease.Adv Ren Replace Ther. 2003; 10: 48-60Abstract Full Text PDF PubMed Scopus (124) Google Scholar Sexual dysfunction related to hypogonadism that starts when a patient has moderate CKD often does not improve with institution of dialysis.32Johansen K.L. Treatment of hypogonadism in men with chronic kidney disease.Adv Chronic Kidney Dis. 2004; 4: 348-356Abstract Full Text Full Text PDF Scopus (27) Google Scholar Despite the wide prevalence of hypogonadism in CKD, there is little information on the use of androgens to treat hypogonadism in CKD. General principles of treatment include adequate nutritional intake, use of rHuEPO, and, in patients with ESRD, ensuring an adequate dose of dialysis.28Palmer B.F. Sexual dysfunction in men and women with chronic kidney disease and end-stage renal disease.Adv Ren Replace Ther. 2003; 10: 48-60Abstract Full Text PDF PubMed Scopus (124) Google Scholar Testosterone therapy is indicated in adult men as treatment of clinical problems because of hypogonadism. Clomiphene citrate has also been used to increase testosterone levels, with improvement in sexual function.28Palmer B.F. Sexual dysfunction in men and women with chronic kidney disease and end-stage renal disease.Adv Ren Replace Ther. 2003; 10: 48-60Abstract Full Text PDF PubMed Scopus (124) Google Scholar Oral testosterone and testosterone derivatives are not used because of their lack of efficacy and adverse effects on liver function and lipid profile32Johansen K.L. Treatment of hypogonadism in men with chronic kidney disease.Adv Chronic Kidney Dis. 2004; 4: 348-356Abstract Full Text Full Text PDF Scopus (27) Google Scholar; parenteral and transdermal testosterone preparations are the commonly used agents. Testosterone enanthate and cipionate are stored in adipose tissue and have effects for 2 to 4 weeks after intramuscular injection. However, serum testosterone fluctuates between injections. Permeability enhanced testosterone transdermal patches and gel formulations can be used to deliver steady levels of testosterone via nonscrotal skin.32Johansen K.L. Treatment of hypogonadism in men with chronic kidney disease.Adv Chronic Kidney Dis. 2004; 4: 348-356Abstract Full Text Full Text PDF Scopus (27) Google Scholar, 33Meikle A. Mazer N. Moellmer J. et al.Enhanced transdermal delivery of testosterone across nonscrotal skin produces physiological concentrations of testosterone and its metabolites in hypogonadal men.J Clin Endocrinol Metab. 1992; 74: 623-628Crossref PubMed Scopus (121) Google Scholar, 34Meikle A. Arver S. Dobs A. et al.Pharmacokinetics and metabolism of a permeation-enhanced testosterone transdermal system in hypogonadal men: Influence of application site—A clinical research center study.J Clin Endocrinol Metab. 1996; 81: 1832-1840Crossref PubMed Scopus (119) Google Scholar Testosterone replacement improves libido, sexual function, mood, and energy,32Johansen K.L. Treatment of hypogonadism in men with chronic kidney disease.Adv Chronic Kidney Dis. 2004; 4: 348-356Abstract Full Text Full Text PDF Scopus (27) Google Scholar, 35Wang C. Swedloff R. Iranmanesh A. et al.Transdermal testosterone gel improves sexual function, mood, muscle strength and body composition parameters in hypogonadal men Testosterone gel study group.J Clin Endocrinol Metab. 2000; 85: 2839-2853Crossref PubMed Scopus (767) Google Scholar, 36Morley J. Perry 3rd, H. Kaiser F. et al.Effect of testosterone replacement therapy in older hypogonadal males: A preliminary study.J Am Geriatr Soc. 1993; 41: 149-152Crossref PubMed Scopus (417) Google Scholar but the effect on libido is more pronounced than the effect on erectile response. Data on use of testosterone in patients with ESRD are limited, and several studies suggest that erectile function in the ESRD population does not improve with testosterone.32Johansen K.L. Treatment of hypogonadism in men with chronic kidney disease.Adv Chronic Kidney Dis. 2004; 4: 348-356Abstract Full Text Full Text PDF Scopus (27) Google Scholar The response of ESRD patients to testosterone may be modulated by the patient's nutritional status, activity level, and growth hormone levels. Testosterone replacement may adversely affect the lipid profile. The effects on lipid profile depend on the age of the patient, dose of androgens, route of administration, and duration of use.37Wu F. Eckardstein A.V. Androgens and coronary artery disease.Endocr Rev. 2003; 24: 183-217Crossref PubMed Scopus (516) Google Scholar Changes in lipid profile include decreases in high-density lipoprotein, fibrinogen, and lipoprotein(a) with smaller decreases seen in triglycerides and low-density lipoprotein. Intramuscular injections seem to have a more significant impact on lipid profile. The overall impact of testosterone treatment on cardiovascular disease remains uncertain. Testosterone may potentiate prostate cancer and increase prostate volume, exacerbating symptoms of benign prostate hypertrophy.32Johansen K.L. Treatment of hypogonadism in men with chronic kidney disease.Adv Chronic Kidney Dis. 2004; 4: 348-356Abstract Full Text Full Text PDF Scopus (27) Google Scholar Hepatotoxicity with jaundice and altered liver functions are usually seen with oral alkylated preparations, warranting periodic liver function testing.32Johansen K.L. Treatment of hypogonadism in men with chronic kidney disease.Adv Chronic Kidney Dis. 2004; 4: 348-356Abstract Full Text Full Text PDF Scopus (27) Google Scholar Other adverse effects are polycythemia (seen in 6%-25% of patients treated with testosterone) and exacerbation of sleep apnea.32Johansen K.L. Treatment of hypogonadism in men with chronic kidney disease.Adv Chronic Kidney Dis. 2004; 4: 348-356Abstract Full Text Full Text PDF Scopus (27) Google Scholar, 36Morley J. Perry 3rd, H. Kaiser F. et al.Effect of testosterone replacement therapy in older hypogonadal males: A preliminary study.J Am Geriatr Soc. 1993; 41: 149-152Crossref PubMed Scopus (417) Google Scholar Sildenafil is a potent and selective inhibitor of guanosine monophosphate–specific phosphodiesterase type 5, the enzyme metabolizing cyclic guanosine monophosphate in the corpus cavernosum, which allows for facilitated flow of blood to the penis.28Palmer B.F. Sexual dysfunction in men and women with chronic kidney disease and end-stage renal disease.Adv Ren Replace Ther. 2003; 10: 48-60Abstract Full Text PDF PubMed Scopus (124) Google Scholar Sildenafil citrate is now the first-line agent for treatment of ED and is effective in patients with ESRD with 65% to 80% of patients reporting improvement.38Rosas S.E. Wasserstein A. Kobrin S. et al.Preliminary observations of sildenafil treatment for erectile dysfunction in dialysis patients.Am J Kidney Dis. 2001; 37: 134-137Abstract Full Text PDF PubMed Scopus (45) Google Scholar, 39Chen J. Mabjeesh N.J. Greenstein A. et al.Clinical efficacy of sildenafil in patients on chronic dialysis.J Urol. 2001; 165: 819-821Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar, 40Barrou B. Cuzin B. Malavaud B. et al.Early experience with sildenafil for the treatment of erectile dysfunction in renal transplant recipients.Nephrol Dial Transplant. 2003; 18: 411-417Crossref PubMed Scopus (37) Google Scholar Sildenafil has similar efficacy in patients on hemodialysis and peritoneal dialysis.28Palmer B.F. Sexual dysfunction in men and women with chronic kidney disease and end-stage renal disease.Adv Ren Replace Ther. 2003; 10: 48-60Abstract Full Text PDF PubMed Scopus (124) Google Scholar, 41Turk S. Karalezli G. Tonbul H.Z. et al.Erectile dysfunction and the effects of sildenafil treatment in patients on hemodialysis and continuous ambulatory peritoneal dialysis.Nephrol Dial Transplant. 2001; 16: 1818-1822Crossref PubMed Scopus (79) Google Scholar It is now common practice to use sildenafil in patients with ED with further evaluation reserved for those patients who are nonresponders to sildenafil. Sildenafil should be used with caution in patients with coronary artery disease and is contraindicated in patients using organic nitrates. To minimize effects of sildenafil on blood pressure, some advocate its use only on nondialysis days.28Palmer B.F. Sexual dysfunction in men and women with chronic kidney disease and end-stage renal disease.Adv Ren Replace Ther. 2003; 10: 48-60Abstract Full Text PDF PubMed Scopus (124) Google Scholar Improvement in sexual function has been reported after transplantation,22Raiz L. Davies E.A. Ferguson R.M. Sexual functioning following renal transplantation.Health Soc Work. 2003; 28: 264-272Crossref PubMed Scopus (42) Google Scholar with 85% to 90% of both men and women kidney transplant recipients reporting improvement in libido.22Raiz L. Davies E.A. Ferguson R.M. Sexual functioning following renal transplantation.Health Soc Work. 2003; 28: 264-272Crossref PubMed Scopus (42) Google Scholar, 42Ghahramani N. Behzadi A. Gholami S. et al.Post renal transplant improvement of sexual function.Transplant Proc. 1999; 31: 3144Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar Restoration of normal sexual function is most common in younger patients.43Tsujimura A, Matsumiya K, Tsuboniwa N, et al: Effect of renal transplantation on sexual function. Arch Androl 48:467-474, 1002Google Scholar Moderate improvements in libido and frequency of sexual intercourse are reported after transplantation and have been linked to normalization of hormonal profiles.43Tsujimura A, Matsumiya K, Tsuboniwa N, et al: Effect of renal transplantation on sexual function. Arch Androl 48:467-474, 1002Google Scholar The hormonal profile in patients with ESRD (low testosterone levels in men and high FSH, LH, and prolactin levels in both men and women) is often reversed with a successful kidney transplant.44Saha M.T. Saha H.H. Niskanen L.K. et al.Time course of serum prolactin and sex hormones following successful renal transplantation.Nephron. 2002; 92: 735-737Crossref PubMed Scopus (83) Google Scholar Regular menstrual cycles are restored in a majority of premenopausal women after a successful kidney transplant, and ovulatory cycles are similar to those of healthy age-matched women. Mean estradiol levels in the follicular phase of the cycle are significantly higher in transplant patients compared with their dialysis-dependent counterparts.45Pietrzak B. Wielgos M. Kaminski P. et al.Menstrual cycle and sex hormone profile in kidney-transplanted women.Neuro Endocrinol Lett. 2006; 27: 198-202PubMed Google Scholar Significantly lower levels of progesterone and testosterone have been observed in kidney transplant recipients.45Pietrzak B. Wielgos M. Kaminski P. et al.Menstrual cycle and sex hormone profile in kidney-transplanted women.Neuro Endocrinol Lett. 2006; 27: 198-202PubMed Google Scholar Sperm counts and morphology do not appear to change after transplant, although sperm motility has been shown to improve.46Akbari F. Alavi M. Esteghamath A. et al.Effects of renal transplantation on sperm quality and sex hormone levels.Br J Urol. 2003; 92: 281-283Crossref Scopus (83) Google Scholar Calcineurin inhibitors (cyclosporine and tacrolimus) have favorable hormonal effects in men after kidney transplantation, although there have been no reported differences in sexual function between cyclosporine and tacrolimus-treated patients.47Kantarci G. Sahin S. Uras A.R. et al.Effects of different calcineurin inhibitors on sex hormone levels in transplanted male patients.Transplant Proc. 2004; 35: 178-179Abstract Full Text Full Text PDF Scopus (30) Google Scholar There are little data about the effects of immunosuppressive medications on hormonal profiles in women. However, sexual dysfunction may remain common after kidney transplantation and is reported by 45% of patients.22Raiz L. Davies E.A. Ferguson R.M. Sexual functioning following renal transplantation.Health Soc Work. 2003; 28: 264-272Crossref PubMed Scopus (42) Google Scholar, 48Diemont W.L. Vruffink P.A. Mueleman E.I.H. et al.Sexual function after renal replacement therapy.Am J Kidney Dis. 2000; 35: 845-851Abstract Full Text Full Text PDF PubMed Scopus (127) Google Scholar Erectile dysfunction, hypoactive sexual desire, and diminished sexual satisfaction are the most commonly encountered problems. Sexual dysfunction is common in patients with kidney disease and often adversely affects quality of life. It is strongly associated with increasing age, dyslipidemia, and depression. The evaluation of sexual function should be included in the clinical assessment of patients with CKD. Particular attention to fertility and contraception are important in patients after kidney transplantation. The management of sexual dysfunction in CKD requires a multifaceted approach. Ensuring optimal delivery of dialysis, adequate nutritional intake, and screening for and management of underlying depression is important. Correction of anemia with rHuEPO has been shown to improve sexual function. Control of secondary hyperparathyroidism with vitamin D may help by lowering prolactin levels and improving sexual function in some patients. Additional definitive pharmacologic therapy of sexual dysfunction in patients with ESRD must be individualized.
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