1Department of Endocrinology and Metabolic Diseases, 2Department of Urology, Larissa University Hospital, Medical School, University of Thessaly, Larissa Greece
Diabetes mellitus (DM) is a common disease worldwide and a growing public health burden. The number of people with diabetes is increasing due to population growth, aging, urbanization, and increasing prevalence of obesity and physical inactivity.1 Diabetes is known to cause multiple medical,2 psychological,3 and sexual4 dysfunctions. Increased prevalence of diabetes will inevitably result in increasing prevalence of its complications and their associated consequences.
Impaired sexual function in men is a well-documented complication of diabetes. The first mention of this disorder was made in the 10th century AD when the Persian physician and philosopher Avicenna described the “collapse of sexual functions” in men with diabetes.5 Numerous presentday studies have shown that men with diabetes are indeed at increased risk for erectile dysfunction, which occurs at an earlier age6-10 than in non-diabetics and is related to duration of diabetes, poor metabolic control, and the presence of diabetic complications.11 Sexual dysfunction can be the first sign of the disease and also an indication of the patient’s vascular status.
In contrast, sexual problems of women with diabetes and associated risk factors are less clear and have received less attention than those of men,12 despite the fact that the risk for developing diabetic complications is the same in men and women with diabetes. Nevertheless, data on the sexual function of diabetic women have recently been published indicating that women with diabetes are also at increased risk for sexual dysfunction.4,13 Discrepancies, however, still exist regarding the prevalence of female sexual dysfunction (FSD) in women with diabetes and the possible mechanisms implicated in its pathogenesis, although both organic and psychological factors seem to act synergistically.
This review aims to discuss diabetic FSD, while defining the parameters of dysfunction, and to present suggested risk factors and pathogenetic pathways as well as offer evidence-based strategies for the evaluation of sexual dysfunction and management.
FEMALE SEXUAL DYSFUNCTION: DEFINITION, PREVALENCE, AND ETIOLOGIES
Female sexual function is complex and encompasses physical and emotional well-being across the lifespan. In general, studies of sexual dysfunction in women have lagged behind those in men due to several factors, the lack of standardized definitions of sexual dysfunction in women being one of them. Understanding the effect of diabetes on FSD presupposes knowledge of the various ways through which FSD has been defined and of the contribution of the ongoing changes to the conceptualization of sexual disorders.
Masters and Johnson in the early 1950’s14 and Kaplan in the late 1970’s15 defined human sexual response based on studies of the physiology and psychology of human sexuality. They developed the linear sexual response model for men and women that consists of sequential stages of desire, arousal, orgasm, and resolution.16,17 Thus, non-overlapping phases of sexual response have been described and according to this model discrete dysfunctions have been defined. However, over the past two decades research on women’s sexual problems have resulted in expanded definitions of women’s sexual dysfunctions due to the highly contextual nature of women’s sexuality. These new definitions continue to reflect phases of sexual response, but they additionally clarify the tendency of the phases to overlap.16,18 The newly defined models of female sexual response include physical, emotional, and cognitive feedback.19 Over the last few years, evidence has emerged supporting the inclusion of ‘‘distress’’ in the definition of FSD;20 however, the interpretation of the term “distress” can vary according to the woman’s perception, from a persistent deterioration of the female psychology to a simple concern.5
Three classical medical definitions for FSD are generally accepted and have been provided by well recognized medical resources. The ICD-10 classification focuses on physical factors that influence sexual response,21 the Diagnostic and Statistical Manual (DSM) – IV underlines the emotional and psychological factors involved in FSD,22 and the most recent classification from the American Foundation of Urological Disease (AFUD) combines the previous classifications with the newest cyclic sexual response model proposed by Basson.23 Newer and revised definitions of FSD by the American Psychiatric Association are expected to be published in their 2012 DSM – V.
Thus the prevalence rates of FSD differ in the various studies, depending on the criteria applied for its definition. Despite these uncertainties, sexual dysfunction in women seems to be more common than once thought. Large epidemiological studies of sexual attitudes and behaviours in men and women showed sexual difficulties to be common in middle-aged adults worldwide24 and in women the reported rates to range between 40-60% in women.25-28 Laumann et al25 reported that 43% of women in the United States, aged 18 to 59 years, had sexual concerns. Dennerstein et al showed that FSD prevalence increased from 42% to 88% from the early to late menopause period.29 The addition of sexual distress in the definition of FSD results in lower prevalence rates (9%) in the general population. Although data are scant and there is a great deal of uncertainty, lack of subjective arousal has been observed in 17% of women,30 insufficient vaginal lubrication in 5-28%,25,30,31 orgasmic disorder in 5%,32 and dyspareunia (painful intercourse) in 3-12%.25,30-33
The etiology of women’s sexual dysfunction is multifactorial and combines interpersonal, contextual (social), psychological, and biological factors.34 In fact, every factor implicated in normal female sexual function can be a potential sexual dysfunction cause, while there is a strong association with psychological health issues25,35,36 such as depression, anxiety, low self-esteem issues, body image perception disorders, fear of rejection, sexual performance anxiety, traumatic sexual experience in the past, and history of abuse. A second major factor is the quality of the relationship.35 Only recently have biological risk factors received attention, including several medical conditions (urogenital, neurological, and endocrine disorders, pelvic floor disorders, menopause, pregnancy, obesity) as well as pharmacological and other therapies (antineoplasmic agents, antipsychotic and antidepressant medications, antihypertensive agents, major surgical operations, radiation therapies).37 Finally, limited social relations, financial difficulties, employment status, religious beliefs, educational background, and lack of exercise38 comprise the sociocultural risk factors of FSD.39
DIABETES MELLITUS AND FEMALE SEXUAL DYSFUNCTION
Despite the inconsistency that exists in the literature concerning this issue, it seems evident that the effect of diabetes on female sexuality is variable and could affect all the domains of sexual function. A mixed pattern of dysfunctional symptoms has commonly been reported, such as reduction or loss of sexual interest or desire, arousal or lubrication difficulties, dyspareunia, and loss of the ability to reach orgasm.13 Studies in the literature conducted in several ethnic groups (US, Italian, Polish, Turkish, Iranian, Jordanian, Nigerian, Peruvian populations) have reported a high prevalence of sexual dysfunction in women with either type 1 or type 2 diabetes.40-53 These data are important since various cultures, religions, lifestyle habits and sexual behaviours are considered. Although the prevalence varies (Table 1 )40,42-53 depending on the criteria used to define sexual dysfunction in each study, it appears that sexual dysfunction is slightly lower in women compared to men,13,54,55 it is twice that of the population without diabetes,13,40,45,48,56 and it includes all the domains of sexual dysfunction. Whether desire is affected by diabetes remains controversial as some studies have shown a 20-78% decrease in desire in women with diabetes (with the higher prevalence encountered in type 2 diabetes), while others have found no effect at all.43-45,47,51,52 The incidence of arousal problems in women with diabetes is also variable, depending on the type of diabetes and the definition of arousal, and varies from 14 to 76% to no effect at all.42-47,49,51,52 Regarding orgasm, most studies have indicated problems in women with diabetes ranging from 10-84%,43-46,49 with a few studies showing no effect.56 Finally, the risk of dyspareunia in women with diabetes varies from zero to 43%, with the higher prevalence being observed in type 2 diabetes.42,49,50
PATHOGENESIS OF FEMALE SEXUAL DYSFUNCTION IN DIABETES
The pathogenetic factors of sexual dysfunction among diabetic women include hyperglycaemia, infections, as well as vascular, neural, neurovascular and psychosocial derangements. However, pertinent data in the few published studies are conflicting.5,13,60,61
It has been hypothesized that hyperglycaemia, by reducing hydration of mucus membranes, including those in the vaginal tissue, results in poor vaginal lubrication and dyspareunia.62 Also, hyperglycaemia may potentially lead to dyspareunia because of its association with an increased incidence of genitourinary infections. The symptoms of these infections (burning, itching, urgency, vaginal dryness or discharge, pain, general discomfort in the pelvic floor), the required treatment, the sexual abstinence recommended as part of some therapies, and the psychological distress involved could lead to vaginal discomfort and dyspareunia.
The normal female sexual response requires an intact sensory and autonomic nervous system to ensure proper interpretation of and response to erotic stimuli. Sexual arousal largely depends on the sympathetic nervous system. Moreover, nonadrenergic/noncholinergic neurotransmitters (NANC), e.g. vasoactive intestinal polypeptide (VIP) and nitric oxide (NO), are involved in smooth muscle relaxation and enhancement of genital blood flow and thus may influence sexual function. Diabetes causes vascular and nerve dysfunction which can lead to structural and functional changes in female genitalia and may impair sexual response.
Over the past two decades, advances have been made in exploring the basic hemodynamics and neuroregulation of female sexual function and dysfunction in both animal models and human studies. Studies in animals have indicated that diabetes, by inducing structural and functional changes in the female genital tract, may result in impaired arousal and orgasmic sexual response.63,64 In a rat model of streptozotocin-induced diabetes it has been shown that diabetes impaired the relaxation responses of the vaginal tissue to almost all transmitter systems [i.e. to electrical stimulation of nerves (EFS), to NO donors, and to calcitonin gene-related peptide (CGRP)] and the contractile response of vaginal tissue to norepinephrine and to EFS.65 Other rat studies have indicated that diabetes causes a significant decrease in nerve-stimulated clitoral and vaginal blood flow, induces diffuse fibrosis of the clitoris and the vaginal tissue, and reduces muscular layer and epithelial thickness in the vagina,63,64,66 thus impairing sexual response. Studies in humans, using vaginal plethysmography as an objective measure of physiological arousal, have found an association between diabetes and decreased vaginal lubrication.48,67 Moreover, in diabetic women a reduced vibration sense in their genitalia has been observed, but whether this symptom is related to sexual problems needs to be clarified.60 Vascular changes or damage due to diabetes may lead to changes in the local blood flow and inhibition of the engorgement of the clitoris and lubrication of the vagina during arousal, resulting in dyspareunia or decreased arousal during sexual activity.63,66 Additionally, the presence of diabetic neuropathy can have detrimental effects on the normal transduction of sexual stimuli as well as on the triggered sexual response61,68 and may cause changes to the vaginal wall and pelvic floor dysfunction as a result of the weakened muscular tone. Arousal, orgasmic, and sexual pain disorders comprise the main consequences of the diabetic neuropathy.
Within the central nervous system, hypothalamic, limbic-hippocampal structures play a central role in sexual arousal. Furthermore, various hormones such as estrogens, testosterone, and progesterone may influence female sexual function. Estrogens play a significant role in maintaining the mucosal epithelium, the sensory thresholds, and the genitalial blood flow, and thus are important for desire.37 Androgens primarily affect sexual desire, arousal, and orgasm and the overall sense of well-being, while progesterone seems to play a role in enhancing receptivity.37 It has been suggested that androgen glucuronides, the metabolic derivatives of testosterone and dehydrotestosterone, can be used as a marker for assessing androgenic activity in women. Moreover, recent data have shown that compared to testosterone or dehydrotestosterone, the glucuronides could identify cases of true androgen deficiency that might be related to sexual dysfunction and possibly require androgen therapy.69 Hormonal imbalance that accompanies DM has been hypothesized to play a potential role in the pathogenesis of the FSD. Epidemiological studies conducted in female diabetic populations have shown a correlation between the observed changes in the levels of androgens, oestrogens, and sex hormone binding globulin (SHBG) and the desire and arousal problems in these women.70 Additionally, several other endocrinopathies that may accompany diabetes, such as thyroid disorders, hypothalamic-pituitary disorders, and polycystic ovary syndrome, can contribute to sexual problems in these women.12 In a recent study, decreased sexual function and increased sexual distress was observed during the luteal phase of the menstrual cycle in women with type 1 diabetes. In this study the decreased sexual function during the luteal phase was independent of mood deflections and glycaemic control.71 More studies are obviously needed to define the effect of the various phases of the menstrual cycle on sexual function.
Depression seems to be the most established risk factor for sexual dysfunction in women with diabetes, especially considering that this cohort is at a high risk of developing depression.72 Several studies have demonstrated that in women with diabetes, sexual dysfunction is predominantly linked to psychological factors.40,47,48,62,73,74 Studies have also revealed that diabetic women with sexual dysfunction presented twice as many depressive symptoms as those without sexual dysfunction. In these women depression was related not only to decreased desire but also to arousal dysfunction.40 However, there are no data as to whether the sexual problems disappear when depression is treated in women with diabetes. Furthermore, diabetes and its complications can harm the woman’s self-image and self-confidence, her health and relationship status, her social life and daily routine, all of which could affect her sexual performance.75
Thus, in general, sexual dysfunction in women with diabetes appears to be quite complex, involving neurological, vascular, hormonal, and psychosocial aspects. Specific risk factors, however, including those related to DM, are difficult to identify. In contrast to studies in men, studies in diabetic women have indicated poor or no association between sexual problems and diabetes related parameters, such as cardiovascular, metabolic (i.e. glycemic control, diabetes duration) or other factors (i.e. age, BMI, menopause, use of hormone replacement therapy),40-42,46-48,56,58,62,74-76 and have shown that their sexual response is more likely affected by psychosocial aspects (e.g. depression).45,48,77 Several factors account for the differences in sex risk factor profiles in men and women. Differences in the underlying pathophysiological mechanisms, such as differences in neurotransmitter involvement of sexual response in men and women,78,79 might be implicated. Furthermore, although it is easy to quantify men’s physiological sexual response by their erection, it is much more difficult for many women to recognise and appraise genital arousal and congestion.5,77,78,80-83 Additionally, cultural and psychosocial factors seem to play a significant role in female sexuality, while depression is a more prevalent and potentially more powerful factor in women as compared to men.84
In general, the available data are controversial and the precise etiology and pathogenetic pathways of diabetes related female sexual disorders have not as yet been determined. Studies of sexual dysfunction in women with diabetes are few and have significant methodological drawbacks in that they include small sample sizes, lack standardized definitions of sexual dysfunction and well-validated scales and, finally, are inadequate in their characterization of diabetes, particularly with regard to type and glycemic control, existence of complications, psychological adjustment to diabetes, and presence or absence of depression.13,84,85 Additionally, variation and differences in sexual dysfunction have been found between the two types of diabetes, although many studies have made no distinction between the two types. Women with type 2 diabetes seem to face more sexual problems in comparison to those with type 1. Older age, age-related factors such as menopause, chronic disease, higher degree of complications, and higher depression rates reported in women with type 2 diabetes may account for these differences.4,62,75,86,87 Moreover, most studies make no distinction between pre- and post-menopausal women, while others exclude women with no relationship. In fact, women with no current sexual relationship might be those with the most severe sexual problems and distress that force them to avoid long-term relationships.
DIAGNOSTIC APPROACH TO DIABETIC FEMALES WITH SEXUAL DYSFUNCTION
Assessing a woman’s sexual function and its disorders can be very challenging. A free talk about her sexual life and its problems may develop into an uncomfortable discussion for both the doctor and the patient. Personal taboos regarding sex, confidentiality issues, worries about potential humiliation, time constraints, even the doctor’s limited experience in handling sexual problems, are a few of the factors that can impede the uncovering of possible sexual difficulties or disorders. Moreover, since many of the causes of FSD do not have a strict medical origin, one has to be careful when characterizing all woman’s sexual problems as organic, as this can lead to mistaken diagnoses and further complicate their management.
To identify whether a diabetic woman has sexual dysfunction and prescribe appropriate treatment, factors that contribute to sexual dysfunction, such as the woman’s current interpersonal and psychosocial status, her sexual and medical history, comorbid illness as well as her medication should be examined.31,88 Sexual dysfunction can be a symptom of an underlying disorder or have causes outside the patient herself. To begin with, a thorough general medical history is essential. The physician should be aware not only of the duration of diabetes, the glycemic control, the presence or absence of chronic diabetic complications, the pharmacological treatment of diabetes but mainly the mood of the diabetic woman as this is the key to the whole process of her sexual enjoyment.67 Even minor episodes of depression can affect the woman’s sexual desire. Poor diabetic control or diabetic complications may cause depression and thus sexual dysfunction in women with diabetes. Hypoglycemia can also impair sexual function in a diabetic woman, as arousal, foreplay, intercourse, and orgasm are all activities of energy expenditure. Comorbid factors, history of surgical operations, medication use, menopausal status, personal habits such as smoking, alcohol intake, and type of exercise can provide useful information on the possible risk factors. During the general systems enquiry, questions about sexual function can follow the gynecological history. If a woman acknowledges sexual problems, a detailed interview of her and her partner both individually and together is usually necessary. The age of initiation of sexual activity, enquiries about sexual abuse or other traumatic sexual experiences, number of sexual partners, impact of religious and social beliefs on sexuality should be taken into account. Moreover, information about the couple’s current sexual life, practices, and complaints along with the degree of satisfaction that results from the sexual activity should be obtained.
In order to facilitate medical practice in the field of sexual medicine, several tools that estimate female sexual function have been developed. To assist physicians in the initial approach and evaluation of sexual function, two simple models have been proposed, namely ALLOW and PLISSIT (Table 2 ).37,89 For a more detailed and extensive evaluation, structured interviews and self-reported validated questionnaires are the most commonly used methods. Structured interviews have a more personal character as they provide the opportunity for clarifying possible details, answering questions, and explaining terms; moreover, the physician has the chance to evaluate the patient’s reactions during the interview. Validated questionnaires on the other hand are characterized by privacy and confidentiality, are adjusted to the female population, and can include measurable data that can be further analyzed.90 The Female Sexual Function Index (FSFI), the Brief Index of Sexual Functioning for Women (BISF-W), the Derogatis Interview for Sexual Function (DISF/DISF – SR) and the Female Sexual Distress Scale (FSDS) are some of the available questionnaires that evaluate female sexual function and its disorders.91 Nevertheless, because of the complexity of the female sexual function, resistant cases of FSD require a multidisciplinary approach, preferably conducted by appropriately trained physicians and specialists.92
THERAPEUTIC APPROACH TO SEXUAL DYSFUNCTION IN WOMEN WITH DIABETES
There are no specific guidelines for the treatment of FSD in diabetic women. Due to the large number of factors that can lead to sexual dysfunction in women with diabetes, effective treatment may entail psychological as well as pharmacological treatment, both applied by trained clinicians. Pharmacotherapy alone without addressing psychosocial issues has been proven to be unsuccessful.93 In general, FSD that is identified early in the sexual response cycle and/or with long duration becomes more resistant to treatment. This means that the orgasmic disorder is easier to handle as compared with arousal or desire dysfunctions.94
Psychological issues, such as previous sexual education and experiences, relationship issues, anxiety and depression, and the mechanisms the patient has developed to cope with diabetes and life in general (seeking medical help, social or spiritual support, friendship, relaxing, pragmatism, anger, aversion) should be addressed. Cognitive-behavioral psychotherapy is the proposed treatment for women suffering from desire disorders or vaginismus, while couple therapy has been proven to result in greater partner intimacy.37,95 Women with arousal or orgasm disorders can benefit from the FDA approved Eros clitoral therapy device.37,96-100 The device is placed over the clitoris and creates a gentle vacuum that increases the genital blood flow, enhancing the genital sensitivity. The InterStim system is a nerve stimulation method originally intended as treatment for urine incontinence; it is now being tested for arousal disorders without, however, definite results.101
Treatment of depression is crucial for the diabetic women with sexual dysfunction, while appropriate and specific antidepressive medications are beneficial.37 Frequently, since improvement of the glycaemic control tends to improve depressive symptoms, antidepressive medications can be discontinued.102 Adequate glycaemic control is of paramount importance for the treatment of sexual dysfunction of diabetic women, who are encouraged to follow their antidiabetic treatment in order to ensure good glycaemic control and avoid complications. Furthermore, lifestyle changes such as implementation of a healthy and balanced diet, regular exercise, and body weight control are suggested not only for achieving better glucose levels but because they have been found to improve female sexual function.95
Pharmacological treatment for FSD is also available and current treatment options are based on hormonal therapies and agents that act either centrally or peripherally. However, further research is needed in this domain for design of improved treatments. The choice of the appropriate medication depends on the type of sexual dysfunction.
The finding that hormonal replacement therapy improves sexual function parameters of menopausal women has led to the use of estrogens for the treatment of FSD, in general. Estrogens may improve sexual function by inducing the proliferation of the superficial cell layer of the vaginal mucosa, improving the vaginal pH and elasticity, and increasing vaginal blood flow to enhance lubrication.103 However, when estrogens are used, the risks of such therapy should be taken into consideration, while careful choice of the most appropriate agent and route of administration are of major importance.95,103,104 Importantly, in women with diabetes the effects of estrogens on lipid profile should be taken seriously into account.105 Studies have established the role of testosterone in female sexual desire, arousal, genital sensation, and orgasm. Thus, finding that FSD is related to androgens deficiency should result in the systematic or topical use of testosterone for its management.106 Testosterone seems to improve desire, arousal, and orgasm; however, due to its side effects, such as masculinization as well as adverse hepatic and cardiovascular effects, the long-term use for the treatment of the FSD is not recommended and further research is needed to establish its action and safety.103,106
Several other pharmaceutical therapies have been suggested. Tibolone has androgenic, estrogenic, and progesterone activity and it has been shown to improve desire, arousal, and lubrication.95,103,107 Phentolamine is an a-antagonist that improves arousal and lubrication;108 apomorphine,94 a-melanocyte-stimulating hormones,109 serotonin receptor antagonists,110 and selective estrogen and androgen receptor modulators are in phase II trials.112 Vasodilators as L-arginin,112 alprostadile,113 and herbal therapy (gingko biloba)112 have an as yet undetermined role in the treatment of FSD.
Phosphodiesterase type 5 inhibitors block the degradative action of type 5 phosphodiesterase on the cyclic GMP (second messenger in the NO mediated smooth muscle relaxation) and amplify vasodilatation.104 Theoretically, they can assist the vaginal and clitoral vasodilation, improving vaginal lubrication and vulvar engorgement. Sildenafil use has had ambiguous results,114 while the role of vardenafil and tadalafil in the treatment of FSD is still to be determined.104 It has been proposed that the low levels of type 5 phosphodiesterase in the female reproductive system could account for these findings.115
DM seems to impair women’s normal sexual functioning. Recent evidence indicates that diabetic women are at higher risk for developing sexual dysfunction compared to those without diabetes. Type 2 diabetes seems to have a greater negative impact on female sexuality than type 1. It nevertheless remains unclear which domain of the sexual cycle is most affected in women with diabetes, the precise mechanisms via which diabetes adversely affects sexual function, and the importance of diabetes-related risk factors on the pathogenesis of FSD. However, current evidence indicates that psychosocial rather than organic factors are implicated in the pathogenesis of the sexual dysfunction in women with diabetes. Physicians should be aware of the problem and address issues of sexuality when they examine women with diabetes. They should be trained to use appropriate methodology for evaluating women’s sexual function in order to identify pertinent pathology and refer them for the appropriate therapeutic approach. Thus, treatment for sexual dysfunctions of diabetic women includes lifestyle changes, optimal diabetic control, psychotherapy, and appropriately selected pharmacotherapy. Further research is obviously necessary to investigate the effects of the different types of diabetes on female sexuality so as to provide effective management options for these women.
Potential conflicts of interest: None.
No grants received.
1. Wild S, Roglic G, Green A, Sicree R, King H, 2004 Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 27: 1047-1053.
2. Anon, 1993 The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med 329: 977-986.
3. Ryan CM Psychological factors and diabetes mellitus. In Textbook of Diabetes Pickup J, Williams G, (eds) Oxford, U.K., Blackwell Science 1997, pp; 1-17.
4. Thomas AM, LoPiccolo J, 1994 Sexual functioning in persons with diabetes: Issues in research, treatment, and education. Clinical Psychology Review 14: 61-86.
5. Giraldi A, Kristensen E. 2010 Sexual dysfunction in women with diabetes mellitus. J Sex Res 47: 199-211.
6. Veves A, Webster L, Chen TF, Payne S, Boulton AJ, 1995 Aetiopathogenesis and management of impotence in diabetic males: four years experience from a combined clinic. Diabet Med 12: 77-82.
7. McCulloch DK, Campbell IW, Wu FC, Prescott RJ, Clarke BF. 1980 The prevalence of diabetic impotence. Diabetologia 18: 279-283.
8. Close CF, Ryder RE, 1995 Impotence in diabetes mellitus. Diabetes Metab Rev 11: 279-285.
9. Webster L, 1994 Management of sexual problems in diabetic patients. Br J Hosp Med 51: 465-468.
10. Feldman HA, Goldstein I, Hatzichristou DG, Krane RJ, McKinlay JB, 1994 Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol 151: 54-61.
11. Fedele D, Bortolotti A, Coscelli C, et al, 2000 Erectile dysfunction in type 1 and type 2 diabetics in Italy. On behalf of Gruppo Italiano Studio Deficit Erettile nei Diabetici. Int J Epidemiol 29: 524-531.
12. Bhasin S, Enzlin P, Coviello A, Basson R, 2007 Sexual dysfunction in men and women with endocrine disorders. Lancet 369: 597-611.
13. Enzlin P, Mathieu C, Vanderschueren D, Demyttenaere K, 1998 Diabetes mellitus and female sexuality: a review of 25 years’ research. Diabet Med 15: 809-815.
14. Masters WH, Johnson VE (eds), 1966 Human Sexual Response. 1st ed. Lippincott Williams & Wilkins, Boston, pp; 1-366.
15. Kaplan HS (ed) 1979 Disorders of Sexual Desire And Other New Concepts and Techniques in Sex Therapy. Brunner-Mazel Inc, New York, pp; 1-237.
16. Basson R, 2000 The female sexual response: a different model. J Sex Marital Ther 26: 51-65.
17. Berman JR, Adhikari SP, Goldstein I, 2000 Anatomy and physiology of female sexual function and dysfunction: classification, evaluation and treatment options. Eur Urol 38: 20-29.
18. Basson R, Leiblum S, Brotto L, et al, 2004 Revised definitions of women’s sexual dysfunction. J Sex Med 1:40-48.
19. Marnach ML, Casey PM, 2008 Understanding women’s sexual health: a case-based approach. Mayo Clin Proc 83: 1382-1386; quiz 1387.
20. Hayes RD, Bennett CM, Fairley CK, Dennerstein L, 2006 What can prevalence studies tell us about female sexual difficulty and dysfunction? J Sex Med 3: 589-595.
21. Anon. Accessed October 9, 2010 WHO | International Classification of Diseases (ICD). Available at: http://www.who.int/classifications/icd/en/
22. Association AP (eds) 2000. In: Diagnostic and Statistical Manual of Mental Disorders DSM-IV-TR Fourth Edition. 4th ed. American Psychiatric Publishing, Washington DC, pp; 535-583.
23. Basson R, Leiblum S, Brotto L, et al, 2003 Definitions of women’s sexual dysfunction reconsidered: advocating expansion and revision. J Psychosom Obstet Gynaecol 24: 221-229.
24. Laumann EO, Nicolosi A, Glasser DB, et al, 2005 Sexual problems among women and men aged 40-80y: prevalence and correlates identified in the Global Study of Sexual Attitudes and Behaviors. Int J Impot Res 17: 39-57.
25. Laumann EO, Paik A, Rosen RC, 1999 Sexual dysfunction in the United States: prevalence and predictors. JAMA 281: 537-544.
26. Lewis RW, Fugl-Meyer KS, Bosch R, et al, 2004 Epidemiology/risk factors of sexual dysfunction. J Sex Med 1: 35-39.
27. Simons JS, Carey MP, 2001 Prevalence of sexual dysfunctions: results from a decade of research. Arch Sex Behav 30: 177-219.
28. Nazareth I, Boynton P, King M, 2003 Problems with sexual function in people attending London general practitioners: cross sectional study. BMJ 327: 423.
29. Dennerstein L, Randolph J, Taffe J, Dudley E, Burger H, 2002 Hormones, mood, sexuality, and the menopausal transition. Fertil Steril 77:Suppl 4: 42-48.
30. Cain VS, Johannes CB, Avis NE, et al, 2003 Sexual functioning and practices in a multi-ethnic study of midlife women: baseline results from SWAN. J Sex Res 40: 266-276.
31. Fugl-Meyer AR, Fugl-Meyer K, 2006 Sexual disabilities, problems and satisfaction in 18-74 year old Swedes. Scand J Sexology 2: 79-105.
32. Ventegodt S, 1998 Sex and the quality of life in Denmark. Arch Sex Behav 27: 295-307.
33. Harlow BL, Stewart EG, 2003 A population-based assessment of chronic unexplained vulvar pain: have we underestimated the prevalence of vulvodynia? J Am Med Womens Assoc 58: 82-88.
34. Berman JR. 2005 Physiology of female sexual function and dysfunction. Int J Impot Res 17 Suppl 1: S44-51.
35. Bancroft J, Loftus J, Long JS, 2003 Distress about sex: a national survey of women in heterosexual relationships. Arch Sex Behav 32: 193-208.
36. Cyranowski JM, Bromberger J, Youk A, et al, 2004 Lifetime depression history and sexual function in women at midlife. Arch Sex Behav 33: 539-548.
37. Frank JE, Mistretta P, Will J, 2008 Diagnosis and treatment of female sexual dysfunction. Am Fam Physician 77: 635-642.
38. Woodard TL, Diamond MP, 2009 Physiologic measures of sexual function in women: a review. Fertil Steril 92: 19-34.
39. Basson R, Berman J, Burnett A, et al, 2000 Report of the international consensus development conference on female sexual dysfunction: definitions and classifications. J Urol 163: 888-893.
40. Enzlin P, Mathieu C, Van den Bruel A, et al, 2002 Sexual dysfunction in women with type 1 diabetes: a controlled study. Diabetes Care 25: 672-677.
41. Erol B, Tefekli A, Ozbey I, et al,2002 Sexual dysfunction in type II diabetic females: a comparative study. J Sex Marital Ther 28: Suppl 1: 55-62.
42. Olarinoye J, Olarinoye A, 2008 Determinants of sexual function among women with type 2 diabetes in a Nigerian population. J Sex Med 5: 878-886.
43. Abu Ali RM, Al Hajeri RM, Khader YS, Shegem NS, Ajlouni KM, 2008 Sexual dysfunction in Jordanian diabetic women. Diabetes Care 31: 1580-1581.
44. Fatemi SS, Taghavi SM, 2009 Evaluation of sexual function in women with type 2 diabetes mellitus. Diab Vasc Dis Res 6: 38-39.
45. Enzlin P, Mathieu C, Van Den Bruel A, Vanderschueren D, Demyttenaere K 2003 Prevalence and predictors of sexual dysfunction in patients with type 1 diabetes. Diabetes Care 26: 409-414.
46. Doruk H, Akbay E, Cayan S, et al, 2005 Effect of diabetes mellitus on female sexual function and risk factors. Arch Androl 51: 1-6.
47. Mezones-Holguin E, Blumel JE, Huezo M, et al, 2008 Impact of diabetes mellitus on the sexuality of Peruvian postmenopausal. Gynecol Endocrinol 24: 470-474.
48. Enzlin P, Rosen R, Wiegel M, et al, 2009 Sexual dysfunction in women with type 1 diabetes: long-term findings from the DCCT/ EDIC study cohort. Diabetes Care 32: 780-785.
49. Veronelli A, Mauri C, Zecchini B, et al, 2009 Sexual dysfunction is frequent in premenopausal women with diabetes, obesity, and hypothyroidism, and correlates with markers of increased cardiovascular risk. A preliminary report. J Sex Med 6: 1561-1568.
50. Wallner LP, Sarma AV, Kim C, 2009 Sexual Functioning among Women with and without Diabetes in the Boston Area Community Health Study. J Sex Med 7: 881-887.
51. Ogbera AO, Chinenye S, Akinlade A, Eregie A, Awobusuyi J, 2009 Frequency and correlates of sexual dysfunction in women with diabetes mellitus. J Sex Med 6: 3401-3406.
52. Nowosielski K, Drosdzol A, Sipinski A, Kowalczyk R, Skrzypulec V, 2010 Diabetes mellitus and sexuality–does it really matter? J Sex Med 7: 723-735.
53. Esposito K, Maiorino MI, Bellastella G, et al, 2010 Determinants of female sexual dysfunction in type 2 diabetes. Int J Impot Res 22: 179-184.
54. Guay AT, 2001 Sexual dysfunction in the diabetic patient. Int J Impot Res 13 Suppl 5: 47-50.
55. Jackson G, 2004 Sexual dysfunction and diabetes. Int J Clin Pract 58: 358-362.
56. Dimitropoulos K, Bargiota A, Zachos I, Koukoulis G, Melekos M, Tzortzis V, 2010 Sexual dysfunction in Greek women with type 1 diabetes: A comparative study. J Sex Med 7: supp l6: 452-453.
57. Campbell LV, Redelman MJ, Borkman M, McLay JG, Chisholm DJ, 1989 Factors in sexual dysfunction in diabetic female volunteer subjects. Med J Aust 151: 550-552.
58. Basson R, Rucker B, Laird P, Conry R, 2001 Sexuality of women with diabetes. J Sex Reprod Med: 11-20.
59. Meeking D, Fosbury J, Cradock S, 1997 Assessing the impact of diabetes on female sexuality. Community Nurse 3: 50-52.
60. Erol B, Tefekli A, Sanli O, et al, 2003 Does sexual dysfunction correlate with deterioration of somatic sensory system in diabetic women? Int J Impot Res 15: 198-202.
61. Duby JJ, Campbell RK, Setter SM, White JR, Rasmussen KA, 2004 Diabetic neuropathy: an intensive review. Am J Health Syst Pharm 61: 160-173; quiz 175-176.
62. Rockliffe-Fidler C, Kiemle G, 2003 Sexual function in diabetic women: A psychological perspective. Sexual and Relationship Therapy 18: 143.
63. Park K, Ahn K, Chang JS, et al, 2002 Diabetes induced alteration of clitoral hemodynamics and structure in the rabbit. J Urol 168: 1269-1272.
64. Park K, Ryu SB, Park YI, et al, 2001 Diabetes mellitus induces vaginal tissue fibrosis by TGF-beta 1 expression in the rat model. J Sex Marital Ther 27: 577-587.
65. Giraldi A, Persson K, Werkstrom V, et al, 2001 Effects of diabetes on neurotransmission in rat vaginal smooth muscle. Int J Impot Res 13: 58-66.
66. Kim NN, Stankovic M, Cushman TT, et al, 2006 Streptozotocin-induced diabetes in the rat is associated with changes in vaginal hemodynamics, morphology and biochemical markers. BMC Physiol 6:4.
67. Wincze JP, Albert A, Bansal S, 1993 Sexual arousal in diabetic females: physiological and self-report measures. Arch Sex Behav 22: 587-601.
68. Brown JS, Wessells H, Chancellor MB, et al, 2005 Urologic complications of diabetes. Diabetes Care 28: 177-185.
69. Labrie F, Belanger A, Belanger P, et al, 2006 Androgen glucuronides, instead of testosterone, as the new markers of androgenic activity in women. J Steroid Biochem Mol Biol 99: 182-188.
70. Feldhaus-Dahir M, 2009 The causes and prevalence of hypoactive sexual desire disorder: part I. Urol Nurs 29: 259-260, 263.
71. Salonia A, Lanzi R, Scavini M, et al, 2006 Sexual function and endocrine profile in fertile women with type 1 diabetes. Diabetes Care 29: 312-316.
72. Schram MT, Baan CA, Pouwer F, 2009 Depression and quality of life in patients with diabetes: a systematic review from the European depression in diabetes (EDID) research consortium. Curr Diabetes Rev 5: 112-119.
73. Leedom L, Feldman M, Procci W, Zeidler A,1991 Symptoms of sexual dysfunction and depression in diabetic women. J Diabet Complications 5: 38-41.
74. Newman AS, Bertelson AD, 1986 Sexual dysfunction in diabetic women. J Behav Med 9: 261-270.
75. Schreiner-Engel P, Schiavi RC, Vietorisz D, Smith H, 1987 The differential impact of diabetes type on female sexuality. J Psychosom Res 31: 23-33.
76. Tyrer G, Steel JM, Ewing DJ, et al, 1983 Sexual responsiveness in diabetic women. Diabetologia 24: 166-171.
77. Laan E, Everaerd W, van Berlo R, Rijs L, 1995 Mood and sexual arousal in women. Behav Res Ther 33: 441-443.
78. Chivers ML, Rieger G, Latty E, Bailey JM, 2004 A sex difference in the specificity of sexual arousal. Psychol Sci 15: 736-744.
79. Basson R, 2001 Human sex-response cycles. J Sex Marital Ther 27: 33-43.
80. Chivers ML, Bailey JM. 2005 A sex difference in features that elicit genital response. Biol Psychol 70: 115-120.
81. Laan E, Everaerd W, Evers A, 1995 Assessment of female sexual arousal: response specificity and construct validity. Psychophysiology 32: 476-485.
82. Laan E, Everaerd W, van der Velde J, Geer JH, 1995 Determinants of subjective experience of sexual arousal in women: feedback from genital arousal and erotic stimulus content. Psychophysiology 32: 444-451.
83. Suschinsky KD, Lalumiere ML, Chivers ML, 2009 Sex differences in patterns of genital sexual arousal: measurement artifacts or true phenomena? Arch Sex Behav 38: 559-573.
84. Graham C, Bancroft J 2005 Assessing the prevalence of female sexual dysfunction with surveys: what is feasible? In: Goldstein I, Meston CM, Davis S, Traish A. (eds) Women’s Sexual Function and Dysfunction: Study, Diagnosis and Treatment. 1st ed. Informa Healthcare, New York, pp; 52-60.
85. Althof SE, Rosen RC, DeRogatis L, et al, 2005 Outcome measurement in female sexual dysfunction clinical trials: review and recommendations. J Sex Marital Ther 31: 153-166.
86. Sarkadi A, Rosenqvist U, 2003 Intimacy and women with type 2 diabetes: an exploratory study using focus
group interviews. Diabetes Educ 29: 641-652.
87. Eplov L, Giraldi A, Davidsen M, Garde K, Kamper-Jorgensen F, 2007 Sexual desire in a nationally representative Danish population. J Sex Med 4: 47-56.
88. Basson R, 2005 Women’s sexual dysfunction: revised and expanded definitions. CMAJ 172: 1327-1333.
89. Whitehouse CR, 2009 Sexuality in the older female with diabetes mellitus–a review of the literature. Urol Nurs 29: 11-18, 29; quiz 19.
90. Hatzichristou D, Rosen RC, Derogatis LR, et al, 2010 Recommendations for the clinical evaluation of men and women with sexual dysfunction. J Sex Med 7: 337-348.
91. Jones LR, 2002 The use of validated questionnaires to assess female sexual dysfunction. World J Urol 2: 89-92.
92. Aslan E, Fynes M, 2008 Female sexual dysfunction. Int Urogynecol J Pelvic Floor Dysfunct 19: 293-305.
93. Althof SE, 2010 What’s new in sex therapy (CME). J Sex Med 7: 5-13; quiz 14-15.
94. Pasqualotto EB, Pasqualotto FF, Sobreiro BP, Lucon AM, 2005 Female sexual dysfunction: the important points to remember. Clinics (Sao Paulo) 60: 51-60.
95. Al-Azzawi F, Bitzer J, Brandenburg U, et al, 2010 Therapeutic options for postmenopausal female sexual dysfunction. Climacteric 13: 103-120.
96. Wilson SK, Delk JR, Billups KL, 2001 Treating symptoms of female sexual arousal disorder with the Eros-Clitoral Therapy Device. J Gend Specif Med 4: 54-58.
97. Billups KL, Berman L, Berman J, et al, 2001 A new non-pharmacological vacuum therapy for female sexual dysfunction. J Sex Marital Ther 27: 435-441.
98. Billups KL, 2002 The role of mechanical devices in treating female sexual dysfunction and enhancing the female sexual response. World J Urol 20: 137-141.
99. Munarriz R, Maitland S, Garcia SP, Talakoub L, Goldstein I, 2003 A prospective duplex Doppler ultrasonographic study in women with sexual arousal disorder to objectively assess genital engorgement induced by EROS therapy. J Sex Marital Ther 29: Suppl 1: 85-94.
100. Schroder M, Mell LK, Hurteau JA, et al, 2005 Clitoral therapy device for treatment of sexual dysfunction in irradiated cervical cancer patients. Int J Radiat Oncol Biol Phys 61:1078-1086.
101. Ingber MS, Ibrahim IA, Killinger KA, Diokno AC, Peters KM, 2009 Neuromodulation and female sexual function: does treatment for refractory voiding symptoms have an added benefit? Int Urogynecol J Pelvic Floor Dysfunct 20: 1055-1059.
102. Jovanovic L, 2002 Finally, it is our turn! Diabetes Care 25: 787-788.
103. Wylie K, Malik F, 2009 Review of drug treatment for female sexual dysfunction. Int J STD AIDS 20: 671-674.
104. Raina R, Pahlajani G, Khan S, et al, 2007 Female sexual dysfunction: classification, pathophysiology, and management. Fertil Steril 88: 1273-1284.
105. Stevenson JC. 2009 Type and route of estrogen administration. Climacteric 12: Suppl 1: 86-90.
106. Shifren JL, 2004 The role of androgens in female sexual dysfunction. Mayo Clin Proc 79: Suppl 4: 19-24.
107. Nijland EA, Weijmar Schultz WCM, Nathorst-Boos J, et al, 2008 Tibolone and transdermal E2/NETA for the treatment of female sexual dysfunction in naturally menopausal women: results of a randomized active-controlled trial. J Sex Med 5: 646-656.
108. Rosen RC, Phillips NA, Gendrano NC, Ferguson DM, 1999 Oral phentolamine and female sexual arousal disorder: a pilot study. J Sex Marital Ther 25: 137-144.
109. Safarinejad MR., 2008 Evaluation of the safety and efficacy of bremelanotide, a melanocortin receptor agonist, in female subjects with arousal disorder: a double-blind placebo-controlled, fixed dose, randomized study. J Sex Med 5: 887-897.
110. Kennedy S, 2010 Flibanserin: Initial Evidence of Efficacy on Sexual Dysfunction, in Patients with Major Depressive Disorder. J Sex Med 7: 3449-3459.
111. Kessel B, Nachtigall L, Plouffe L, et al, 2003 Effect of raloxifene on sexual function in postmenopausal women. Climacteric 6: 248-256.
112. Rowland DL, Tai W, 2003 A review of plant-derived and herbal approaches to the treatment of sexual dysfunctions. J Sex Marital Ther 29: 185-205.
113. Liao Q, Zhang M, Geng L, et al, 2008 Efficacy and safety of alprostadil cream for the treatment of female sexual arousal disorder: a double-blind, placebo-controlled study in chinese population. J Sex Med 5: 1923-1931.
114. Brown DA, Kyle JA, Ferrill MJ, 2009 Assessing the clinical efficacy of sildenafil for the treatment of female sexual dysfunction. Ann Pharmacother 43: 1275-1285.
115. Uckert S, Ellinghaus P, Albrecht K, Jonas U, Oelke M, 2007 Expression of messenger ribonucleic acid encoding for phosphodiesterase isoenzymes in human female genital tissues. J Sex Med 4: 1604-1609.
Address for correspondence:
Alexandra Bargiota, Department of Endocrinology and
Metabolic Diseases, Larissa University Hospital, Biopolis,
41110, Larissa, Greece, Tel.: +30 2413 502987,
Fax: +30 2413 501024, e-mail: email@example.com
Received 05-02-11, Revised 18-05-11, Accepted 14-06-11