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PHYSIOLOGY: Periovulatory Morphometric and Vascular Modifications of the Clitoris in Young Adult and Middle-Aged Women. A Pilot Study
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ORIGINAL RESEARCH—ANATOMY/PHYSIOLOGY Periovulatory Morphometric and Vascular Modifications of the Clitoris in Young Adult and Middle-Aged Women. A Pilot Study
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Cesare Battaglia, MD,* Rossella Elena Nappi, MD,† Arianna Cianciosi, MD,* Paolo Busacchi, MD,* Giovanni Sisti, MD,* Roberto Paradisi, MD,* and Stefano Venturoli, MD* *Department of Gynecology and Pathophysiology of Human Reproduction, University of Bologna, Bologna, Italy; † Research Centre for Reproductive Medicine, University of Pavia, Pavia, Italy DOI: 10.1111/j.1743-6109.2009.01402.x
ABSTRACT
Introduction. A decline in sexual activity has been reported as women age. Aim. To compare, in young adult and middle-aged women, the clitoral volumetric and vascular modifications during the periovulatory phase of the menstrual cycle, and to analyze their relationship with circulating hormones, nitric oxide levels, and with questionnaires on sexuality, relationship, and depression. Methods. Fifteen young (18–25 years; Group I), and 16 middle-aged (35–45 years; Group II) eumenorrheic women were submitted, on day 14 of their menstrual cycle, to utero-ovarian and clitoral ultrasonographic analysis, and to color Doppler evaluation of the uterine and dorsal clitoral arteries. On the same day, hormonal parameters and plasma concentrations of nitrites/nitrates were assayed, and the two-factor Italian McCoy female questionnaire and the Beck’s Depression Inventory questionnaire were administered. Main Outcomes Measures. Utero-ovarian and clitoral ultrasonographic analysis, color Doppler evaluation of the uterine and dorsal clitoral arteries; evaluation of hormonal and nitrites/nitrates plasma concentrations; administration of the two-factor Italian McCoy Female Sexuality Questionnaire and the Beck’s Depression Inventory questionnaire. Results. The plasma levels of estradiol, testosterone, sex hormone binding globulin, and nitrites/nitrates were similar in both groups. Neither the ultrasonographic assessment of the clitoral body volume (0.82 ⫾ 0.24 mL vs. 0.73 ⫾ 0.26 mL) nor the Doppler analysis of the dorsal clitoral artery [pulsatility index (PI) = 1.35 ⫾ 0.31 vs. PI = 1.36 ⫾ 0.19] evidenced any significant differences in either Group I or Group II. The two-factor Italian McCoy Female Sexuality Questionnaire and the Beck Depression Inventory questionnaire gave the same results in Group I and Group II. The relationship between the different parameters evidenced that the NO2-/NO3- circulating levels are inversely correlated with uterine artery (r = -0.4611; P = 0.008) and dorsal clitoral artery (r = -0.331; P = 0.041) PIs. Furthermore, estradiol resulted inversely correlated with depression (r = -0.332; P = 0.045). The two sections (sexuality and partnership) of Italian McCoy Female Sexuality Questionnaire were positively correlated (r = 0.849; P < 0.0001) between each other. Conclusions. In eumenorrheic young adult and middle-aged women, the periovulatory clitoral anatomic and vascular modifications similarly occur. Battaglia C, Nappi RE, Cianciosi A, Busacchi P, Sisti G, Paradisi R, and Venturoli S. Periovulatory morphometric and vascular modifications of the clitoris in young adult and middle-aged women. A pilot study. J Sex Med 2009;6:2707–2714. Key Words. Age; Sexuality; Depression; Ultrasound; Doppler
Introduction
S
ex involves: a successful integration between an intact neural, vascular, and muscular circuitry; complex interactions between multiple © 2009 International Society for Sexual Medicine
neurotransmitter systems; and critical modulating influences from the endocrine system. One of the earliest changes in the female sexual excitation is an increase in vulval, clitoral, and vaginal blood flow. The increased blood flow is mediated by J Sex Med 2009;6:2707–2714
2708 autonomic fibers from the hypogastric plexus and the nerve roots S2–S3. Estrogens exert a huge influence on maintaining uro-genital tissue integrity and have local regulatory effects on nerve transmission and vascular mediators [vasoactive intestinal peptide; neuropeptide Y, nitric oxide (NO)] [1,2]. The modifications in clitoral anatomy and blood flow may be objectively evaluated by ultrasonography and color Doppler [3–7]. In the lower mammals, there is a strict relationship between ovarian cycle and sexual behavior such that virtually all sexual activities take place around estrous (the time of maximal fertility). This association is less evident with regard to the sexuality of women and their menstrual cycles. In fact, although Stanislaw and Rice [8] reported that sexual desire is generally experienced a few days before the basal body temperature shift (around the expected ovulation date), and Battaglia et al. [6] showed an increased clitoral vascularization in the periovulatory phase of the menstrual cycle, Meuwissen and Over [9] evidenced that the female sexual response does not vary during the menstrual cycle. Probably in humans, sexual function results are conditioned by education, social position, cultural and religious beliefs, past sexual experiences, relationship duration and satisfaction, partner sexual function, stress, general well-being, use of contraceptives, and other factors. Although healthy young adult and middle-aged women have, in general, stable menstrual cycles and a comparable hormonal milieu, psychorelational and socio-cultural factors varying during the entire reproductive life span (i.e., teen-age, young adulthood, pregnancy and post-partum, lactation, middle-age, perimenopause and menopause) may induce significant changes in female sexual desire, arousal, orgasm, and satisfaction. The aim of the present study was to compare, independently from sexual stimulation, in healthy young adult and middle-aged women, the clitoral volumetric and vascular modification during the periovulatory phase of the menstrual cycle, and to analyze their relationship with circulating hormones, NO levels, and with questionnaires on sexuality, relationship, and depression. Materials and Methods
Study Population Between June and December 2007, 15 young adult (18–25 years; Group I) and 16 middle-aged (35– 45 years; Group II) Caucasian (native Italians) women, who were referred to our Clinic for conJ Sex Med 2009;6:2707–2714
Battaglia et al. traceptive necessities, were recruited into the study. All the enrolled patients, in a pre-screening analysis, were selected among 47 women who resulted: eumenorrheic (menstrual cycle >25 and <35 days); with regular ovulatory cycles documented by ultrasonography (presence of a corpus luteum) and by normal serum midluteal progesterone levels (>15 nmol/L) in the previous cycle; and with a normal body mass index (BMI) (weight in kg/weight in m2; BMI = 19–25). Furthermore, the patients were married or in a stable heterosexual relationships (>1 year). In addition, all subjects were nonsmokers; made no use of psychoactive drugs, recreational substances, or alcohol; did not exercise intensely on a regular basis; and had not received any hormonal therapy for at least 6 months prior to the study. Women with neurological, psychiatric, cardiovascular and endocrine disorders, hypertension (systolic blood pressure >140 mm Hg and/or diastolic pressure >90 mm Hg), hirsutism, diabetes, renal or hepatic illnesses, were excluded from the study. Further exclusion criteria were: uterine malformations, dyspareunia, endometriosis, polycystic ovaries, ovarian functional cyst, unilateral ovarian resection or ovariectomy, urologic and proctologic diseases, and a history of perineal surgery or trauma. The subjects prior to the enrolment undertook a pregnancy test which resulted negative. During the subscription of the informed consent, 16 women refused the enrollment considering the study time-consuming (N = 11) or prejudicial of their privacy (N = 5). An informed consent was obtained from all women who participated in the study. The study protocol was in accordance with the Helsinki II declaration and was approved by the Hospital Research Review Committee. During the first screening evaluation, participants communicated their educational and job status and were assessed with a detailed history and medical examination. The mean BMI was calculated. Patients were further submitted to transvaginal ultrasonography to exclude any uteroovarian pathology. The patients who fulfilled the inclusion criteria were submitted, in the periovulatory phase of the cycle (day 14), to utero-ovarian and clitoral ultrasonographic analysis and to color Doppler evaluation of the uterine, and dorsal clitoral arteries [6]. On the same day, fasting blood samples were drawn for testing hormonal parameters and plasma concentrations of nitrites/nitrates (NO2-/ NO3-). In addition, each woman completed the
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two-factor Italian McCoy Female Sexuality Questionnaire (MFSQ) [10] and the Beck’s Depression Inventory (BDI) questionnaire [11]. On day 20, to assess the ovulatory cycles, we evaluated by ultrasonography the presence or absence of a corpus luteum and the rise in midluteal serum progesterone (>15 nmol/mL).
They rested in a recumbent position and were evaluated between 8:00 and 11:00 am to exclude the effects of hormonal and NO2-/NO3- circadian rhythmicity on blood flow [15,16]. A 50-Hz filter was used to eliminate low-frequency signals originating from vessel wall movements. The maximum Doppler ultrasonography energy was <80 mW/cm2. This intensity is within the safety limits suggested by the American Institute for Ultrasound in Medicine. Color flow images of the ascending branches of the uterine arteries were sampled laterally to the cervix in a longitudinal plane. The angle of insonation was always adjusted to obtain maximum color intensity. When adequate signals were obtained, blood flow velocity waveforms were recorded by placing the sample volume across the vessel and activating the pulsed Doppler mode. The pulsatility index (PI), defined as the difference between the peak systolic and end-diastolic flow divided by the mean maximum flow velocity, was electronically calculated by the machine for the uterine arteries. The PI has been shown to reflect blood flow impedance and may be used when the end-diastolic frequency shift is absent or reversed. For each examination, the mean value of three consecutive waveforms was obtained. No significant differences between the PIs of the left and right side for uterine arteries were observed, and therefore, the average value of both side arteries was used. The correlation between PIs and heart rate was not tested. Immediately after the previously described US and Doppler scanning, the patients were evaluated, in the same noiseless laboratory with constant heat and light, to analyze the clitoral anatomy and the blood flow in the dorsal clitoral artery [6,7]. After that, abundant coupling gel was applied, and a high resolution ultrasound transducer (7–10 MHz multi-frequency linear array transducer-Aspen-) was placed on the upper part of the vulva for the clitoral transverse and axial section and on the labia majora for the sagittal section. To prevent artifacts, care was taken to avoid excessive pressure on the clitoris. The clitoris was studied where the paired corpora join in a single body that projects into the glans [17,18]. The clitoral body volume was calculated. Volumes were measured by reporting length, width, and depth assuming the forms to be ellipsoid, using the formula based on a prolate ellipsoid: V = p/ 6 ¥ D1 ¥ D2 ¥ D3, where D1, D2, and D3 are the maximal longitudinal, antero-posterior, and transverse diameter.
Assays Peripheral blood flow was obtained from all patients between 08.00 and 11.00, after an overnight fast, on the same day that Ultrasound and Doppler examinations took place, and different hormonal and biochemical parameters were analyzed. Plasma concentration of estradiol (E2) and testosterone (T) were assayed (by A.C. and P.B.) as previously described [12,13]. Sex hormone binding globulin (SHBG) was immunoassayed using Immulite 1000 (EURO/Diagnostic Products Corp. Ltd., Los Angeles, CA, USA). The free androgen index (FAI) was calculated using the equations: FAI = T (nmol/L)/SHBG (nmol/ L) ¥ 100. Results of hormonal values were converted to SI units using the following conversion factors: E2 (pmol/L) = pg/mL ¥ 3.761; T (nmol/ l) = ng/mL ¥ 3.467; A (nmol/L) = ng/dL ¥ 0.0349. An aliquot of peripheral blood was immediately centrifuged and its serum stored at –70° until assays were performed. NO production was assessed by monitoring the serum levels of stable oxidation products of NO metabolism (NO2-/ NO3-). As very little or no NO2- is normally found in serum, we did not attempt to differentiate between NO2- and NO3- amounts and therefore we have reported our results as NO2-/NO3-. The NO2-/NO3- were assayed by F.F. and R.E.N., with the Greiss reaction using procedures previously described [14]. The serum NO2-/NO3 values are expressed in mmol/L. Ultrasound and Color Doppler Examination Ultrasonographic (US) examination of the uterine and ovarian morphology was performed with the use of a 6.0–8.0 multi-frequency transvaginal transducer (Aspen, Acuson-Siemens, Milan, Italy). Doppler flow measurements of the uterine vessels were performed transvaginally with a multi-frequency color Doppler system (Aspen color Doppler). To ensure standardized conditions, the patients rested in a waiting room for at least 15 minutes before being scanned. Furthermore, in order to minimize external effects on blood flow, all the patients were scanned in a noiseless laboratory with constant heat and light.
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Battaglia et al.
Color flow images of the dorsal clitoral artery were sampled, in a longitudinal plane, on the outer surface of the clitoral body [6]. Ultrasound and color Doppler analyses were performed by a single examiner (C.B.).
Behavioral Assessment On the same day, in a separate room, and just before that ultrasound and Doppler examinations took place, and the different hormonal and biochemical parameters were analyzed, the patients completed the questionnaires on sexuality and depression [10,11]. The two-factor Italian MFSQ [10] is a validated tool to adequately discriminate between women with and without sexual dysfunction measuring on a 7-point Likert scale twodimensions: sexuality (desire, orgasm, arousal, pain, and satisfaction) and partnership (partner’s sexual health, feeling, and relationship). Female sexual dysfunction was diagnosed with a score <35 for sexuality. The BDI [11] is a well-validated 21-item self-administered rating inventory measuring characteristic attitudes and symptoms of depression (sadness, pessimism, dislike of self, change in body image, fatigability, etc.). The score on each of the 21 questions is 0–3 (absent to severe), and the highest possible total for the whole test is 63. Values up to 9 are considered normal; 10–18 express a mild/moderate depression; 19–29 moderate/severe depression; 30–63 severe depression. Statistical Analysis
Statistical analysis (SPSS 12.0 software, SPSS Inc., Chicago IL, USA) was performed using the
analysis of variance test. The evaluation of educational and job distribution was performed with Z-test for two proportions. The relationship between the parameters analyzed was assessed using the linear regression method. A P value of 0.05 was considered statistically significant. Data are presented as mean ⫾ standard deviation, unless otherwise indicated. The statistical analysis was independently performed by two researchers (N.P., G.S.). Results
All 31 patients completed the study. As expected by inclusion criteria, the mean age was significantly lower in Group I than in Group II women and the BMI index did not show any difference between the groups (Table 1). The hormonal assays, carried out in the periovulatory phase of the cycle (day 14), demonstrated that the plasma levels of E2, and T were similar in both groups (Table 1). The SHBG values and the FAI resulted as reported in Table 1. No significant differences were observed in hormonal and NO2-/ NO3- circulating levels (Table 1). In the mid luteal phase of the cycle (day 20), all the patients showed regular ovulatory cycles as documented by the US evidence of corpus luteum and serum progesterone levels >15 nmol/mL. The US assessment, in the periovulatory phase of the cycle (day 14), allowed an easy evaluation of uterus and ovaries in 100% of the cases. A normal endometrial thickness (Table 2) and an adequate follicular growth (Table 2) were evidenced in both Group I and Group II.
Table 1 Clinical, educational, socioeconomic, hormonal, and biochemical profile in young adult (Group I: 18–25 years) and middle-aged (Group II: 35–45 years) healthy, eumenorrheic women. Statistical analysis was performed using the one-way analysis of variance test. Data are presented as mean ⫾ standard deviation. The evaluation of educational and job distribution was performed using the Z-test for two proportions
Age (years) Body mass index (kg/m2) Education
J Sex Med 2009;6:2707–2714
Group I (N = 15)
Group II (N = 16)
Significance P
23.6 ⫾ 2.6 21.8 ⫾ 2.6
40.2 ⫾ 1.5 21.5 ⫾ 1.9
<0.0001 NS
0/15 10/15 5/15 8/15 5/15 2/15 722 ⫾ 883 1.22 ⫾ 1.01 51 ⫾ 22 2.8 ⫾ 2.0 42.7 ⫾ 22.5
1/16 9/16 6/16 0/16 6/16 10/16 876 ⫾ 409 1.08 ⫾ 0.78 56 ⫾ 19 1.8 ⫾ 1.0 36.4 ⫾ 13.9
-0.041 (NS) 0.226 (NS) -0.133 (NS) 2.98 0.226 (NS) 2.44 NS NS NS NS NS
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Table 2 Ultrasonographic and color Doppler parameters in young adult (Group I: 18–25 years) and middle-aged (Group II: 35–45 years) healthy, eumenorrheic women
Ultrasound Endometrial thickness (mm) Follicular diameter (mm) Clitoral body volume (mL) Color doppler Uterine artery (PI) Dorsal clitoral artery (PI)
Group I (N = 15)
Group II (N = 16)
Significance P
7.8 ⫾ 2.0 17.5 ⫾ 4.6 0.82 ⫾ 0.24
8.7 ⫾ 2.0 17.5 ⫾ 3.5 0.73 ⫾ 0.26
NS NS NS
2.35 ⫾ 0.54 1.35 ⫾ 0.31
2.50 ⫾ 0.55 1.36 ⫾ 0.19
NS NS
NS = not significant; PI = pulsatility index.
In the 31 not sexually aroused women, the US assessment of the clitoral body volume (day 14 of the menstrual cycle) evidenced no significant differences between young adult and middle-aged patients (Table 2). As a result of the Doppler analysis (day 14 of the menstrual cycle), a similar mean uterine pulsatility index was found in Group I and Group II (Table 2). Similarly, the resistances registered at the level of the dorsal clitoral artery did not show any difference between Group I and Group II (Table 2). The mean duration of US and Doppler procedures lasted <15 minutes and no patient claimed any discomfort during the exam. The two-factor Italian MFSQ and the BDI questionnaire resulted similar in both Group I and Group II patients (Figure 1). The relationship between the different parameters evidenced that the NO2-/NO3- circulating levels were inversely correlated with the uterine
Figure 1 The Beck Depression Inventory (BDI) resulted not significantly different in both young adult and middle-aged women. The values were, in both groups, in the normal range (up to 9). Similarly, the two-factor Italian McCoy Female Sexuality Questionnaire (MFSQ) administered for sexuality (Sex) and partnership (Rel) resulted not significantly different among the studied patients. None showed a condition of female sexual dysfunction (a score < 35 for sexuality) either in young adult and middle-aged women.
artery and the dorsal clitoral artery PIs (Table 3). Furthermore, estradiol resulted inversely and significantly correlated with depression (Table 3). In addition, the two sections (sexuality and partnership) of Italian MFSQ were positively and highly significantly correlated (r = 0.849; P ⱕ 0.0001). Discussion
In the young adult women, the risk of academic and social difficulties, the definitive acceptance of body image, and the new feeling of autonomy may contribute to impair the quality of life. In the middle-aged women, the difficulties in the maintenance of a positive self-image, the empty “nest” syndrome, and the difficulties in home or job organization are factors that may have the same negative effects. Furthermore, independently from age, a sense of sexual inadequacy may induce a loss of self-esteem with profound effects on both intimate and social relationships. Although we were aware that the study presents several shortcomings (no evaluations of peri- and postmenopausal women; the number of patients is limited; and that the single US and color Doppler evaluation was arbitrary chosen), in the present study, other than confirming the role of ultrasonography as a noninvasive analysis of the clitoral structures [6,13], we observed that the technique is easy, not time consuming, and is well accepted by the patients. In addition, although clitoral ultrasonography depends on free hand placement and manipulation of the ultrasound probe on the clitoris, we believe that the extreme care we used to not apply any pressure on the studied structures, allowed us to avoid decreasing clitoral artery blood flow and to obtain reproducible results. At the best of our knowledge and for the first time in literature, we showed that, independent of age, in the periovulatory phase of the menstrual cycle of healthy, not sexually aroused, eumenorrheic women, there is no difference in the function J Sex Med 2009;6:2707–2714
2712 Table 3
Battaglia et al. Relationship between different measures analyzed using the linear regression method
Age Body mass index Estradiol FAI Clitoral volume Clitoral dorsal artery Uterine artery NO2-/NO3BDI MFSQ Sex MFSQ Rel
Clitoral r
volume P
Clitoral dorsal r
Artery P
-0.031 0.164 0.174 0.295 = -0.166 0.262 -0.033 0.012 0.201 0.164
0.430 0.390 0.360 0.058 = 0.382 0.067 0.426 0.472 0.127 0.177
-0.078 -0.135 -0.049 0.013 -0.166 = 0.139 -0.331 -0.227 -0.105 -0.030
0.331 0.223 0.392 0.471 0.175 = 0.216 0.041 0.098 0.278 0.434
Estradiol
Age Body mass index Estradiol FAI Clitoral volume Clitoral dorsal artery Uterine artery NO2-/NO3BDI MFSQ Sex MFSQ Rel
FAI
NO2-/NO3-
r
P
r
P
r
P
0.067 0.009 = -0.133 0.174 -0.049 0.114 -0.048 -0.332 0.269 0.237
0.352 0.479 = 0.226 0.360 0.392 0.261 0.393 0.045 0.062 0.088
-0.059 -0.096 -0.133 = 0.295 0.013 -0.285 -0.118 -0.005 -0.101 -0.058
0.370 0.294 0.226 = 0.058 0.471 0.061 0.253 0.488 0.284 0.373
-0.059 -0.136 -0.048 -0.118 -0.033 -0.331 -0.461 = -0.152 0.118 -0.064
0.370 0.222 0.393 0.253 0.426 0.041 0.008 = 0.195 0.254 0.360
BDI = Beck Depression Inventory; FAI = Free Androgen Index; MFSQ = McCoy Female Sexuality Questionnaire; Rel = partnership; Sex = sexuality.
of uterine and clitoral structures. Furthermore, we observed that clitoral volume and vascularization, and circulating estrogen and NO2-/NO3- values were superimposable to those we had found in a previous study using young eumenorrheic women in the periovulatory phase [6]. The role of estrogens in the regulation of female sexual function has been frequently reported. Estrogens are known to be vasoprotective and to regulate the vascular smooth muscle tone. Dennerstein et al. [19] recently demonstrated that “sexual responsivity” (a measure of interest, arousal, enjoyment, and orgasm) improves when, in a spontaneous cycle, estradiol circulating levels are comprised between 650 and 759 pmol/L. These values match those we observed in our patients during the periovulatory period. In addition, we observed that NO2-/NO3circulating levels were inversely correlated with the PIs of the dorsal clitoral artery. We speculated, as did Gragasin et al. [20], that NO, produced by the estrogen-mediated action of NO synthase on L-arginine, induces a rise of cyclic guanosine monophosfate in postjunctional cells and causes a calcium influx to the clitoral vascular smooth muscle. This phenomena cause vasodilatation, relaxation of the clitoral cavernosal tissue, and an increase in the clitoral size. This confirms that J Sex Med 2009;6:2707–2714
estrogens and NO play a key role in the clitoral morpho-functional modifications during the menstrual cycle. The androgens were not different among the studied young adult and middle-aged women. In addition, FAI and testosterone circulating values were not correlated with clitoral volume and vascularization. Thus, we speculated that probably, in eumenorrheic women, the androgens are not involved in modulating the clitoral morphostructural functions. The exact physiological and biochemical role of androgens in female sexual function remains controversial and poorly understood. Whether the effects of androgens are mediated by a direct action on the nervous system, or by an effect on the genital system, or both, has yet to be determined. In women, the role of androgens is confounded by the fact that their synthesis and metabolism take place in the ovaries, the adrenal glands, and the peripheral tissue. Furthermore, active androgens may be locally synthesized in peripheral target tissues by tissue-specific steroidogenic enzymes according to the intracrine process [21–23]. Thus, the levels of circulating androgens may not provide the correct information on the bioavailability of their metabolites. However, it was suggested that androgens have no
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effects on sexual arousal “per se” but may influence other aspects of sexual desire, such as thoughts and fantasies. It is well known that sexuality is far more than a simple biological reaction to visual, auditory, or tactile stimuli; quite often, it has been emphasized that a satisfying sexuality is principally based on psychological factors. In the studied patients, we observed that in the periovulatory period (the phase of maximal production of estrogens during the menstrual cycle), the incidence of depression was nearly absent (BDI values <9). Furthermore, we did not note any sexual dysfunction (as resulting by the two-factor Italian MFSQ: MFSQ = ⱖ35) both in young adult and middleaged women. The partnership section of MFSQ demonstrated high values and resulted significantly correlated with the sexual section. We therefore speculate that, in healthy women, a stable and satisfactory relationship with one’s partner (i.e., characterized by concern for each other’s well-being, a willingness to disclose private information, and commonality of interests and activities) results in reassurance for the females’ psychological well-being and may result confirmatory of their sex appeal.
ultrasonography before and after sexual stimulation in women with sexual dysfunction: Gray scale, volumetric, and hemodynamic findings. Fertil Steril 2005;83:995–9. Nappi RE, Federghini F, Sampaolo P, Vaccaro P, De Leonardis C, Albani F, Salonia A, Polatti F. Clitoral circulation in postmenopausal women with sexual dysfunction: A pilot randomized studt with hormone therapy. Maturitas 2006;55:288–95. Kukkonen TM, Paterson L, Binik YM, Amsel R, Bouvier F, Khalifè S. Convergent and discriminant validity of clitoral color Doppler ultrasonography as a measure of female sexual arousal. J Sex Mar Ther 2006;32:281–7. Battaglia C, Nappi RE, Mancini F, Cianciosi A, Persico N, Busacchi P, Facchinetti F, de Aloysio D. Menstrual cycle-related morphometric and vascular modifications of the clitoris. J Sex Med 2008;5: 2853–61. Buisson O, Foldes P, Paniel BJ. Sonography of the clitoris. J Sex Med 2008;5:413–7. Stanislaw H, Rice FJ. Correlation between sexual desire and menstrual cycle characteristics. Arch Sex Behav 1988;17:499–508. Meuwissen I, Over R. Sexual arousal across phases of the human menstrual cycle. Arch Sex Behav 1992; 21:101–19. Rellini AH, Nappi RE, Vaccaro P, Federghini F, Abbiati I, Meston CM. Validation of the McCoy Female Sexuality Questionnaire in an Italian sample. Arch Sex Behav 2005;34:641–7. Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J. An inventory for measuring depression. Arch Gen Psychiatry 1961;4:561–71. Battaglia C, Regnani G, Mancini F, Iughetti I, Flamigni C, Venturoli S. Polycystic ovaries in childhood: A common finding in daughters of PCOS patients. A pilot study. Hum Reprod 2002;17:771–6. Battaglia C, Nappi RE, Mancini F, Cianciosi A, Persico N, Busacchi P, Facchinetti F, Sisti G. PCOS, sexuality and clitoral vascularization. A pilot study. J Sex Med 2008;5:2886–94. Facchinetti F, De Martis S, Neri I, Caputo A, Volpe A. Effects of transdermal glyceryltrinitate on 24-h blood pressure changes in patients with gestational hypertension. Prenat Neonat Med 1997;2:22–8. Battaglia C, Mancini F, Cianciosi A, Busacchi P, Facchinetti F, Reggiani Marchesini G, Marzocchi R, de Aloysio D. Vascular risk in young women with polycystic ovary and polycystic ovary syndrome. Obstet Gynecol 2008;111:385–95. Zaidi J, Jurcovic D, Campbell S, Okokon E, Tan SL. Circadian variation in uterine artery blood flow indices during the follicular phase of the menstrual cycle. Ultrasound Obstet Gynecol 1995;5:406–10. O’Connel HE, DeLancey JOL. Clitoral anatomy in nulliparous, healthy, premenopausal volunteers using unenhanced magnetic resonance imaging. J Urol 2005;173:2060–3.
Conclusions
The present pilot study evidenced that in eumenorrheic young adult and middle-aged women, the periovulatory clitoral anatomic and vascular modifications occur independently from age. Further, wider and prospective studies are necessary to better analyze the clitoral variations during the entire female reproductive life span.
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Corresponding Author: Cesare Battaglia, MD, Obstetrics and Gynecology,University of Bologna,Via Massarenti, 13, -40138 Bologna, Italy. Tel: 39-0516364377; Fax: 39-051-6364377; E-mail: cesare. [email protected]
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Conflict of Interest: None.
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References
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ORIGINAL RESEARCH—ANATOMY/PHYSIOLOGY Periovulatory Morphometric and Vascular Modifications of the Clitoris in Young Adult and Middle-Aged Women. A Pilot Study
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Cesare Battaglia, MD,* Rossella Elena Nappi, MD,† Arianna Cianciosi, MD,* Paolo Busacchi, MD,* Giovanni Sisti, MD,* Roberto Paradisi, MD,* and Stefano Venturoli, MD* *Department of Gynecology and Pathophysiology of Human Reproduction, University of Bologna, Bologna, Italy; † Research Centre for Reproductive Medicine, University of Pavia, Pavia, Italy DOI: 10.1111/j.1743-6109.2009.01402.x
ABSTRACT
Introduction. A decline in sexual activity has been reported as women age. Aim. To compare, in young adult and middle-aged women, the clitoral volumetric and vascular modifications during the periovulatory phase of the menstrual cycle, and to analyze their relationship with circulating hormones, nitric oxide levels, and with questionnaires on sexuality, relationship, and depression. Methods. Fifteen young (18–25 years; Group I), and 16 middle-aged (35–45 years; Group II) eumenorrheic women were submitted, on day 14 of their menstrual cycle, to utero-ovarian and clitoral ultrasonographic analysis, and to color Doppler evaluation of the uterine and dorsal clitoral arteries. On the same day, hormonal parameters and plasma concentrations of nitrites/nitrates were assayed, and the two-factor Italian McCoy female questionnaire and the Beck’s Depression Inventory questionnaire were administered. Main Outcomes Measures. Utero-ovarian and clitoral ultrasonographic analysis, color Doppler evaluation of the uterine and dorsal clitoral arteries; evaluation of hormonal and nitrites/nitrates plasma concentrations; administration of the two-factor Italian McCoy Female Sexuality Questionnaire and the Beck’s Depression Inventory questionnaire. Results. The plasma levels of estradiol, testosterone, sex hormone binding globulin, and nitrites/nitrates were similar in both groups. Neither the ultrasonographic assessment of the clitoral body volume (0.82 ⫾ 0.24 mL vs. 0.73 ⫾ 0.26 mL) nor the Doppler analysis of the dorsal clitoral artery [pulsatility index (PI) = 1.35 ⫾ 0.31 vs. PI = 1.36 ⫾ 0.19] evidenced any significant differences in either Group I or Group II. The two-factor Italian McCoy Female Sexuality Questionnaire and the Beck Depression Inventory questionnaire gave the same results in Group I and Group II. The relationship between the different parameters evidenced that the NO2-/NO3- circulating levels are inversely correlated with uterine artery (r = -0.4611; P = 0.008) and dorsal clitoral artery (r = -0.331; P = 0.041) PIs. Furthermore, estradiol resulted inversely correlated with depression (r = -0.332; P = 0.045). The two sections (sexuality and partnership) of Italian McCoy Female Sexuality Questionnaire were positively correlated (r = 0.849; P < 0.0001) between each other. Conclusions. In eumenorrheic young adult and middle-aged women, the periovulatory clitoral anatomic and vascular modifications similarly occur. Battaglia C, Nappi RE, Cianciosi A, Busacchi P, Sisti G, Paradisi R, and Venturoli S. Periovulatory morphometric and vascular modifications of the clitoris in young adult and middle-aged women. A pilot study. J Sex Med 2009;6:2707–2714. Key Words. Age; Sexuality; Depression; Ultrasound; Doppler
Introduction
S
ex involves: a successful integration between an intact neural, vascular, and muscular circuitry; complex interactions between multiple © 2009 International Society for Sexual Medicine
neurotransmitter systems; and critical modulating influences from the endocrine system. One of the earliest changes in the female sexual excitation is an increase in vulval, clitoral, and vaginal blood flow. The increased blood flow is mediated by J Sex Med 2009;6:2707–2714
2708 autonomic fibers from the hypogastric plexus and the nerve roots S2–S3. Estrogens exert a huge influence on maintaining uro-genital tissue integrity and have local regulatory effects on nerve transmission and vascular mediators [vasoactive intestinal peptide; neuropeptide Y, nitric oxide (NO)] [1,2]. The modifications in clitoral anatomy and blood flow may be objectively evaluated by ultrasonography and color Doppler [3–7]. In the lower mammals, there is a strict relationship between ovarian cycle and sexual behavior such that virtually all sexual activities take place around estrous (the time of maximal fertility). This association is less evident with regard to the sexuality of women and their menstrual cycles. In fact, although Stanislaw and Rice [8] reported that sexual desire is generally experienced a few days before the basal body temperature shift (around the expected ovulation date), and Battaglia et al. [6] showed an increased clitoral vascularization in the periovulatory phase of the menstrual cycle, Meuwissen and Over [9] evidenced that the female sexual response does not vary during the menstrual cycle. Probably in humans, sexual function results are conditioned by education, social position, cultural and religious beliefs, past sexual experiences, relationship duration and satisfaction, partner sexual function, stress, general well-being, use of contraceptives, and other factors. Although healthy young adult and middle-aged women have, in general, stable menstrual cycles and a comparable hormonal milieu, psychorelational and socio-cultural factors varying during the entire reproductive life span (i.e., teen-age, young adulthood, pregnancy and post-partum, lactation, middle-age, perimenopause and menopause) may induce significant changes in female sexual desire, arousal, orgasm, and satisfaction. The aim of the present study was to compare, independently from sexual stimulation, in healthy young adult and middle-aged women, the clitoral volumetric and vascular modification during the periovulatory phase of the menstrual cycle, and to analyze their relationship with circulating hormones, NO levels, and with questionnaires on sexuality, relationship, and depression. Materials and Methods
Study Population Between June and December 2007, 15 young adult (18–25 years; Group I) and 16 middle-aged (35– 45 years; Group II) Caucasian (native Italians) women, who were referred to our Clinic for conJ Sex Med 2009;6:2707–2714
Battaglia et al. traceptive necessities, were recruited into the study. All the enrolled patients, in a pre-screening analysis, were selected among 47 women who resulted: eumenorrheic (menstrual cycle >25 and <35 days); with regular ovulatory cycles documented by ultrasonography (presence of a corpus luteum) and by normal serum midluteal progesterone levels (>15 nmol/L) in the previous cycle; and with a normal body mass index (BMI) (weight in kg/weight in m2; BMI = 19–25). Furthermore, the patients were married or in a stable heterosexual relationships (>1 year). In addition, all subjects were nonsmokers; made no use of psychoactive drugs, recreational substances, or alcohol; did not exercise intensely on a regular basis; and had not received any hormonal therapy for at least 6 months prior to the study. Women with neurological, psychiatric, cardiovascular and endocrine disorders, hypertension (systolic blood pressure >140 mm Hg and/or diastolic pressure >90 mm Hg), hirsutism, diabetes, renal or hepatic illnesses, were excluded from the study. Further exclusion criteria were: uterine malformations, dyspareunia, endometriosis, polycystic ovaries, ovarian functional cyst, unilateral ovarian resection or ovariectomy, urologic and proctologic diseases, and a history of perineal surgery or trauma. The subjects prior to the enrolment undertook a pregnancy test which resulted negative. During the subscription of the informed consent, 16 women refused the enrollment considering the study time-consuming (N = 11) or prejudicial of their privacy (N = 5). An informed consent was obtained from all women who participated in the study. The study protocol was in accordance with the Helsinki II declaration and was approved by the Hospital Research Review Committee. During the first screening evaluation, participants communicated their educational and job status and were assessed with a detailed history and medical examination. The mean BMI was calculated. Patients were further submitted to transvaginal ultrasonography to exclude any uteroovarian pathology. The patients who fulfilled the inclusion criteria were submitted, in the periovulatory phase of the cycle (day 14), to utero-ovarian and clitoral ultrasonographic analysis and to color Doppler evaluation of the uterine, and dorsal clitoral arteries [6]. On the same day, fasting blood samples were drawn for testing hormonal parameters and plasma concentrations of nitrites/nitrates (NO2-/ NO3-). In addition, each woman completed the
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two-factor Italian McCoy Female Sexuality Questionnaire (MFSQ) [10] and the Beck’s Depression Inventory (BDI) questionnaire [11]. On day 20, to assess the ovulatory cycles, we evaluated by ultrasonography the presence or absence of a corpus luteum and the rise in midluteal serum progesterone (>15 nmol/mL).
They rested in a recumbent position and were evaluated between 8:00 and 11:00 am to exclude the effects of hormonal and NO2-/NO3- circadian rhythmicity on blood flow [15,16]. A 50-Hz filter was used to eliminate low-frequency signals originating from vessel wall movements. The maximum Doppler ultrasonography energy was <80 mW/cm2. This intensity is within the safety limits suggested by the American Institute for Ultrasound in Medicine. Color flow images of the ascending branches of the uterine arteries were sampled laterally to the cervix in a longitudinal plane. The angle of insonation was always adjusted to obtain maximum color intensity. When adequate signals were obtained, blood flow velocity waveforms were recorded by placing the sample volume across the vessel and activating the pulsed Doppler mode. The pulsatility index (PI), defined as the difference between the peak systolic and end-diastolic flow divided by the mean maximum flow velocity, was electronically calculated by the machine for the uterine arteries. The PI has been shown to reflect blood flow impedance and may be used when the end-diastolic frequency shift is absent or reversed. For each examination, the mean value of three consecutive waveforms was obtained. No significant differences between the PIs of the left and right side for uterine arteries were observed, and therefore, the average value of both side arteries was used. The correlation between PIs and heart rate was not tested. Immediately after the previously described US and Doppler scanning, the patients were evaluated, in the same noiseless laboratory with constant heat and light, to analyze the clitoral anatomy and the blood flow in the dorsal clitoral artery [6,7]. After that, abundant coupling gel was applied, and a high resolution ultrasound transducer (7–10 MHz multi-frequency linear array transducer-Aspen-) was placed on the upper part of the vulva for the clitoral transverse and axial section and on the labia majora for the sagittal section. To prevent artifacts, care was taken to avoid excessive pressure on the clitoris. The clitoris was studied where the paired corpora join in a single body that projects into the glans [17,18]. The clitoral body volume was calculated. Volumes were measured by reporting length, width, and depth assuming the forms to be ellipsoid, using the formula based on a prolate ellipsoid: V = p/ 6 ¥ D1 ¥ D2 ¥ D3, where D1, D2, and D3 are the maximal longitudinal, antero-posterior, and transverse diameter.
Assays Peripheral blood flow was obtained from all patients between 08.00 and 11.00, after an overnight fast, on the same day that Ultrasound and Doppler examinations took place, and different hormonal and biochemical parameters were analyzed. Plasma concentration of estradiol (E2) and testosterone (T) were assayed (by A.C. and P.B.) as previously described [12,13]. Sex hormone binding globulin (SHBG) was immunoassayed using Immulite 1000 (EURO/Diagnostic Products Corp. Ltd., Los Angeles, CA, USA). The free androgen index (FAI) was calculated using the equations: FAI = T (nmol/L)/SHBG (nmol/ L) ¥ 100. Results of hormonal values were converted to SI units using the following conversion factors: E2 (pmol/L) = pg/mL ¥ 3.761; T (nmol/ l) = ng/mL ¥ 3.467; A (nmol/L) = ng/dL ¥ 0.0349. An aliquot of peripheral blood was immediately centrifuged and its serum stored at –70° until assays were performed. NO production was assessed by monitoring the serum levels of stable oxidation products of NO metabolism (NO2-/ NO3-). As very little or no NO2- is normally found in serum, we did not attempt to differentiate between NO2- and NO3- amounts and therefore we have reported our results as NO2-/NO3-. The NO2-/NO3- were assayed by F.F. and R.E.N., with the Greiss reaction using procedures previously described [14]. The serum NO2-/NO3 values are expressed in mmol/L. Ultrasound and Color Doppler Examination Ultrasonographic (US) examination of the uterine and ovarian morphology was performed with the use of a 6.0–8.0 multi-frequency transvaginal transducer (Aspen, Acuson-Siemens, Milan, Italy). Doppler flow measurements of the uterine vessels were performed transvaginally with a multi-frequency color Doppler system (Aspen color Doppler). To ensure standardized conditions, the patients rested in a waiting room for at least 15 minutes before being scanned. Furthermore, in order to minimize external effects on blood flow, all the patients were scanned in a noiseless laboratory with constant heat and light.
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Battaglia et al.
Color flow images of the dorsal clitoral artery were sampled, in a longitudinal plane, on the outer surface of the clitoral body [6]. Ultrasound and color Doppler analyses were performed by a single examiner (C.B.).
Behavioral Assessment On the same day, in a separate room, and just before that ultrasound and Doppler examinations took place, and the different hormonal and biochemical parameters were analyzed, the patients completed the questionnaires on sexuality and depression [10,11]. The two-factor Italian MFSQ [10] is a validated tool to adequately discriminate between women with and without sexual dysfunction measuring on a 7-point Likert scale twodimensions: sexuality (desire, orgasm, arousal, pain, and satisfaction) and partnership (partner’s sexual health, feeling, and relationship). Female sexual dysfunction was diagnosed with a score <35 for sexuality. The BDI [11] is a well-validated 21-item self-administered rating inventory measuring characteristic attitudes and symptoms of depression (sadness, pessimism, dislike of self, change in body image, fatigability, etc.). The score on each of the 21 questions is 0–3 (absent to severe), and the highest possible total for the whole test is 63. Values up to 9 are considered normal; 10–18 express a mild/moderate depression; 19–29 moderate/severe depression; 30–63 severe depression. Statistical Analysis
Statistical analysis (SPSS 12.0 software, SPSS Inc., Chicago IL, USA) was performed using the
analysis of variance test. The evaluation of educational and job distribution was performed with Z-test for two proportions. The relationship between the parameters analyzed was assessed using the linear regression method. A P value of 0.05 was considered statistically significant. Data are presented as mean ⫾ standard deviation, unless otherwise indicated. The statistical analysis was independently performed by two researchers (N.P., G.S.). Results
All 31 patients completed the study. As expected by inclusion criteria, the mean age was significantly lower in Group I than in Group II women and the BMI index did not show any difference between the groups (Table 1). The hormonal assays, carried out in the periovulatory phase of the cycle (day 14), demonstrated that the plasma levels of E2, and T were similar in both groups (Table 1). The SHBG values and the FAI resulted as reported in Table 1. No significant differences were observed in hormonal and NO2-/ NO3- circulating levels (Table 1). In the mid luteal phase of the cycle (day 20), all the patients showed regular ovulatory cycles as documented by the US evidence of corpus luteum and serum progesterone levels >15 nmol/mL. The US assessment, in the periovulatory phase of the cycle (day 14), allowed an easy evaluation of uterus and ovaries in 100% of the cases. A normal endometrial thickness (Table 2) and an adequate follicular growth (Table 2) were evidenced in both Group I and Group II.
Table 1 Clinical, educational, socioeconomic, hormonal, and biochemical profile in young adult (Group I: 18–25 years) and middle-aged (Group II: 35–45 years) healthy, eumenorrheic women. Statistical analysis was performed using the one-way analysis of variance test. Data are presented as mean ⫾ standard deviation. The evaluation of educational and job distribution was performed using the Z-test for two proportions
Age (years) Body mass index (kg/m2) Education
J Sex Med 2009;6:2707–2714
Group I (N = 15)
Group II (N = 16)
Significance P
23.6 ⫾ 2.6 21.8 ⫾ 2.6
40.2 ⫾ 1.5 21.5 ⫾ 1.9
<0.0001 NS
0/15 10/15 5/15 8/15 5/15 2/15 722 ⫾ 883 1.22 ⫾ 1.01 51 ⫾ 22 2.8 ⫾ 2.0 42.7 ⫾ 22.5
1/16 9/16 6/16 0/16 6/16 10/16 876 ⫾ 409 1.08 ⫾ 0.78 56 ⫾ 19 1.8 ⫾ 1.0 36.4 ⫾ 13.9
-0.041 (NS) 0.226 (NS) -0.133 (NS) 2.98 0.226 (NS) 2.44 NS NS NS NS NS
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Table 2 Ultrasonographic and color Doppler parameters in young adult (Group I: 18–25 years) and middle-aged (Group II: 35–45 years) healthy, eumenorrheic women
Ultrasound Endometrial thickness (mm) Follicular diameter (mm) Clitoral body volume (mL) Color doppler Uterine artery (PI) Dorsal clitoral artery (PI)
Group I (N = 15)
Group II (N = 16)
Significance P
7.8 ⫾ 2.0 17.5 ⫾ 4.6 0.82 ⫾ 0.24
8.7 ⫾ 2.0 17.5 ⫾ 3.5 0.73 ⫾ 0.26
NS NS NS
2.35 ⫾ 0.54 1.35 ⫾ 0.31
2.50 ⫾ 0.55 1.36 ⫾ 0.19
NS NS
NS = not significant; PI = pulsatility index.
In the 31 not sexually aroused women, the US assessment of the clitoral body volume (day 14 of the menstrual cycle) evidenced no significant differences between young adult and middle-aged patients (Table 2). As a result of the Doppler analysis (day 14 of the menstrual cycle), a similar mean uterine pulsatility index was found in Group I and Group II (Table 2). Similarly, the resistances registered at the level of the dorsal clitoral artery did not show any difference between Group I and Group II (Table 2). The mean duration of US and Doppler procedures lasted <15 minutes and no patient claimed any discomfort during the exam. The two-factor Italian MFSQ and the BDI questionnaire resulted similar in both Group I and Group II patients (Figure 1). The relationship between the different parameters evidenced that the NO2-/NO3- circulating levels were inversely correlated with the uterine
Figure 1 The Beck Depression Inventory (BDI) resulted not significantly different in both young adult and middle-aged women. The values were, in both groups, in the normal range (up to 9). Similarly, the two-factor Italian McCoy Female Sexuality Questionnaire (MFSQ) administered for sexuality (Sex) and partnership (Rel) resulted not significantly different among the studied patients. None showed a condition of female sexual dysfunction (a score < 35 for sexuality) either in young adult and middle-aged women.
artery and the dorsal clitoral artery PIs (Table 3). Furthermore, estradiol resulted inversely and significantly correlated with depression (Table 3). In addition, the two sections (sexuality and partnership) of Italian MFSQ were positively and highly significantly correlated (r = 0.849; P ⱕ 0.0001). Discussion
In the young adult women, the risk of academic and social difficulties, the definitive acceptance of body image, and the new feeling of autonomy may contribute to impair the quality of life. In the middle-aged women, the difficulties in the maintenance of a positive self-image, the empty “nest” syndrome, and the difficulties in home or job organization are factors that may have the same negative effects. Furthermore, independently from age, a sense of sexual inadequacy may induce a loss of self-esteem with profound effects on both intimate and social relationships. Although we were aware that the study presents several shortcomings (no evaluations of peri- and postmenopausal women; the number of patients is limited; and that the single US and color Doppler evaluation was arbitrary chosen), in the present study, other than confirming the role of ultrasonography as a noninvasive analysis of the clitoral structures [6,13], we observed that the technique is easy, not time consuming, and is well accepted by the patients. In addition, although clitoral ultrasonography depends on free hand placement and manipulation of the ultrasound probe on the clitoris, we believe that the extreme care we used to not apply any pressure on the studied structures, allowed us to avoid decreasing clitoral artery blood flow and to obtain reproducible results. At the best of our knowledge and for the first time in literature, we showed that, independent of age, in the periovulatory phase of the menstrual cycle of healthy, not sexually aroused, eumenorrheic women, there is no difference in the function J Sex Med 2009;6:2707–2714
2712 Table 3
Battaglia et al. Relationship between different measures analyzed using the linear regression method
Age Body mass index Estradiol FAI Clitoral volume Clitoral dorsal artery Uterine artery NO2-/NO3BDI MFSQ Sex MFSQ Rel
Clitoral r
volume P
Clitoral dorsal r
Artery P
-0.031 0.164 0.174 0.295 = -0.166 0.262 -0.033 0.012 0.201 0.164
0.430 0.390 0.360 0.058 = 0.382 0.067 0.426 0.472 0.127 0.177
-0.078 -0.135 -0.049 0.013 -0.166 = 0.139 -0.331 -0.227 -0.105 -0.030
0.331 0.223 0.392 0.471 0.175 = 0.216 0.041 0.098 0.278 0.434
Estradiol
Age Body mass index Estradiol FAI Clitoral volume Clitoral dorsal artery Uterine artery NO2-/NO3BDI MFSQ Sex MFSQ Rel
FAI
NO2-/NO3-
r
P
r
P
r
P
0.067 0.009 = -0.133 0.174 -0.049 0.114 -0.048 -0.332 0.269 0.237
0.352 0.479 = 0.226 0.360 0.392 0.261 0.393 0.045 0.062 0.088
-0.059 -0.096 -0.133 = 0.295 0.013 -0.285 -0.118 -0.005 -0.101 -0.058
0.370 0.294 0.226 = 0.058 0.471 0.061 0.253 0.488 0.284 0.373
-0.059 -0.136 -0.048 -0.118 -0.033 -0.331 -0.461 = -0.152 0.118 -0.064
0.370 0.222 0.393 0.253 0.426 0.041 0.008 = 0.195 0.254 0.360
BDI = Beck Depression Inventory; FAI = Free Androgen Index; MFSQ = McCoy Female Sexuality Questionnaire; Rel = partnership; Sex = sexuality.
of uterine and clitoral structures. Furthermore, we observed that clitoral volume and vascularization, and circulating estrogen and NO2-/NO3- values were superimposable to those we had found in a previous study using young eumenorrheic women in the periovulatory phase [6]. The role of estrogens in the regulation of female sexual function has been frequently reported. Estrogens are known to be vasoprotective and to regulate the vascular smooth muscle tone. Dennerstein et al. [19] recently demonstrated that “sexual responsivity” (a measure of interest, arousal, enjoyment, and orgasm) improves when, in a spontaneous cycle, estradiol circulating levels are comprised between 650 and 759 pmol/L. These values match those we observed in our patients during the periovulatory period. In addition, we observed that NO2-/NO3circulating levels were inversely correlated with the PIs of the dorsal clitoral artery. We speculated, as did Gragasin et al. [20], that NO, produced by the estrogen-mediated action of NO synthase on L-arginine, induces a rise of cyclic guanosine monophosfate in postjunctional cells and causes a calcium influx to the clitoral vascular smooth muscle. This phenomena cause vasodilatation, relaxation of the clitoral cavernosal tissue, and an increase in the clitoral size. This confirms that J Sex Med 2009;6:2707–2714
estrogens and NO play a key role in the clitoral morpho-functional modifications during the menstrual cycle. The androgens were not different among the studied young adult and middle-aged women. In addition, FAI and testosterone circulating values were not correlated with clitoral volume and vascularization. Thus, we speculated that probably, in eumenorrheic women, the androgens are not involved in modulating the clitoral morphostructural functions. The exact physiological and biochemical role of androgens in female sexual function remains controversial and poorly understood. Whether the effects of androgens are mediated by a direct action on the nervous system, or by an effect on the genital system, or both, has yet to be determined. In women, the role of androgens is confounded by the fact that their synthesis and metabolism take place in the ovaries, the adrenal glands, and the peripheral tissue. Furthermore, active androgens may be locally synthesized in peripheral target tissues by tissue-specific steroidogenic enzymes according to the intracrine process [21–23]. Thus, the levels of circulating androgens may not provide the correct information on the bioavailability of their metabolites. However, it was suggested that androgens have no
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effects on sexual arousal “per se” but may influence other aspects of sexual desire, such as thoughts and fantasies. It is well known that sexuality is far more than a simple biological reaction to visual, auditory, or tactile stimuli; quite often, it has been emphasized that a satisfying sexuality is principally based on psychological factors. In the studied patients, we observed that in the periovulatory period (the phase of maximal production of estrogens during the menstrual cycle), the incidence of depression was nearly absent (BDI values <9). Furthermore, we did not note any sexual dysfunction (as resulting by the two-factor Italian MFSQ: MFSQ = ⱖ35) both in young adult and middleaged women. The partnership section of MFSQ demonstrated high values and resulted significantly correlated with the sexual section. We therefore speculate that, in healthy women, a stable and satisfactory relationship with one’s partner (i.e., characterized by concern for each other’s well-being, a willingness to disclose private information, and commonality of interests and activities) results in reassurance for the females’ psychological well-being and may result confirmatory of their sex appeal.
ultrasonography before and after sexual stimulation in women with sexual dysfunction: Gray scale, volumetric, and hemodynamic findings. Fertil Steril 2005;83:995–9. Nappi RE, Federghini F, Sampaolo P, Vaccaro P, De Leonardis C, Albani F, Salonia A, Polatti F. Clitoral circulation in postmenopausal women with sexual dysfunction: A pilot randomized studt with hormone therapy. Maturitas 2006;55:288–95. Kukkonen TM, Paterson L, Binik YM, Amsel R, Bouvier F, Khalifè S. Convergent and discriminant validity of clitoral color Doppler ultrasonography as a measure of female sexual arousal. J Sex Mar Ther 2006;32:281–7. Battaglia C, Nappi RE, Mancini F, Cianciosi A, Persico N, Busacchi P, Facchinetti F, de Aloysio D. Menstrual cycle-related morphometric and vascular modifications of the clitoris. J Sex Med 2008;5: 2853–61. Buisson O, Foldes P, Paniel BJ. Sonography of the clitoris. J Sex Med 2008;5:413–7. Stanislaw H, Rice FJ. Correlation between sexual desire and menstrual cycle characteristics. Arch Sex Behav 1988;17:499–508. Meuwissen I, Over R. Sexual arousal across phases of the human menstrual cycle. Arch Sex Behav 1992; 21:101–19. Rellini AH, Nappi RE, Vaccaro P, Federghini F, Abbiati I, Meston CM. Validation of the McCoy Female Sexuality Questionnaire in an Italian sample. Arch Sex Behav 2005;34:641–7. Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J. An inventory for measuring depression. Arch Gen Psychiatry 1961;4:561–71. Battaglia C, Regnani G, Mancini F, Iughetti I, Flamigni C, Venturoli S. Polycystic ovaries in childhood: A common finding in daughters of PCOS patients. A pilot study. Hum Reprod 2002;17:771–6. Battaglia C, Nappi RE, Mancini F, Cianciosi A, Persico N, Busacchi P, Facchinetti F, Sisti G. PCOS, sexuality and clitoral vascularization. A pilot study. J Sex Med 2008;5:2886–94. Facchinetti F, De Martis S, Neri I, Caputo A, Volpe A. Effects of transdermal glyceryltrinitate on 24-h blood pressure changes in patients with gestational hypertension. Prenat Neonat Med 1997;2:22–8. Battaglia C, Mancini F, Cianciosi A, Busacchi P, Facchinetti F, Reggiani Marchesini G, Marzocchi R, de Aloysio D. Vascular risk in young women with polycystic ovary and polycystic ovary syndrome. Obstet Gynecol 2008;111:385–95. Zaidi J, Jurcovic D, Campbell S, Okokon E, Tan SL. Circadian variation in uterine artery blood flow indices during the follicular phase of the menstrual cycle. Ultrasound Obstet Gynecol 1995;5:406–10. O’Connel HE, DeLancey JOL. Clitoral anatomy in nulliparous, healthy, premenopausal volunteers using unenhanced magnetic resonance imaging. J Urol 2005;173:2060–3.
Conclusions
The present pilot study evidenced that in eumenorrheic young adult and middle-aged women, the periovulatory clitoral anatomic and vascular modifications occur independently from age. Further, wider and prospective studies are necessary to better analyze the clitoral variations during the entire female reproductive life span.
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Corresponding Author: Cesare Battaglia, MD, Obstetrics and Gynecology,University of Bologna,Via Massarenti, 13, -40138 Bologna, Italy. Tel: 39-0516364377; Fax: 39-051-6364377; E-mail: cesare. [email protected]
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Conflict of Interest: None.
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