Science, University of Catania, Catania, Italy; â¡Unit of Ultrastructural Pathology, Department of Human Pathology,. University of Messina, Messina, Italy.
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Ultrastructural and Quantitative Study of Clitoral Cavernous Tissue from Living Subjects jsm_2253
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Salvatore Caruso, MD,*† Antonio Cianci, MD,† Chiara Malandrino, MD,*† Lidia Cavallari, BS,‡ Orazio Gambadoro, TA,‡ Grazia Arena, BS,‡ Letterio Pispisa, TA,‡ Carmela Agnello, MD,* Mattea Romano, MD,*† and Vittorio Cavallari, MD, PhD‡ *Research Group for Sexology, University of Catania, Catania, Italy; †Department of Mother and Child, and Radiologic Science, University of Catania, Catania, Italy; ‡Unit of Ultrastructural Pathology, Department of Human Pathology, University of Messina, Messina, Italy DOI: 10.1111/j.1743-6109.2011.02253.x
ABSTRACT
Introduction. There has never been an investigation about the in vivo clitoral structure. Aim. To study the “in vivo” age-related structural changes of the clitoris in healthy women and in those affected by metabolic disorders. Methods. Forty-three women subgrouping in (i) five teenagers, aged 14–18; (ii) eight young premenopausal women, aged 23–32; (iii) 10 premenopausal women, aged 38–47; (iv) nine diabetic premenopausal women, aged 27–43; and (v) 11 naturally postmenopausal women aged 51–55. Each woman underwent microbiopsy of the clitoral body by means of an 18G needle, length 100 mm, using a semiautomatic gun during total anesthesia for a benign gynecological pathology. The tissue removed was processed for electron microscopy. A morphometric procedure was used on electron micrographs. Main Outcome Measure. Micro ultrastructure observation of clitoral tissue. Results. The cavernous tissue from the teenagers and young women showed large amounts of smooth muscle cells (SMCs). The intercellular connective tissue showed scanty, small isometric collagen fibers and amorphous extracellular matrix. In the premenopausal diabetic women, ultrastructural abnormalities of SMCs were observed, consisting of increase of glycogen deposits, infolding cell borders, and cytoplasmic vacuoles. Moreover, the intercellular connective tissue was increased by densely packed collagen fibers. Finally, in the healthy, natural postmenopausal women, the SMCs were moderately reduced in number. We observed age-related structural changes of the vascular spaces and of the vascular lacunae. The SMC mean thickness was reduced with age; vascular abnormalities appeared to be correlated with the presence of metabolic diseases, such as diabetes. Conclusion. Our “in vivo” study could help to understand some aspects of the physiology of the clitoris and its role in sexual response. Apart from data obtained by studying healthy women and women affected by diabetes, other investigations are needed to study subgroups of otherwise healthy sexually dysfunctional women. Caruso S, Cianci A, Malandrino C, Cavallari L, Gambadoro O, Arena G, Pispisa L, Agnello C, Romano M, and Cavallari V. Ultrastructural and quantitative study of clitoral cavernous tissue from living subjects. J Sex Med 2011;8:1675–1685. Key Words. Clitoris; Female Sexual Function and Dysfunction; Microbiopsy; Ultrastructure
Introduction
A
lthough there has been some recent progress, advances in understanding the male sexual function and dysfunction have not been paralleled by similar advances in understanding the female sexual function, even in basic anatomy and physi© 2011 International Society for Sexual Medicine
ology. There are still many areas in the field of female sexual physiopathology that remain to be fully studied, among which are disturbances of the excitation phase, particularly the hemodynamics of the clitoral corpora cavernosa. The role of the clitoris in female sexual activity is prominent. Therefore, the hypothesis that structural J Sex Med 2011;8:1675–1685
1676 alterations of this organ could account for sexual problems in premenopausal and postmenopausal women is reasonable. Studies to clarify the anatomy and sexual function/dysfunction involving the clitoris have been less comprehensive than studies of its male counterpart, the penis. The histological anatomy of the human clitoris is often described using cursory or comparative terms. Detailed studies of clitoral anatomy and physiology in animal models have been carried out; even if they are scientifically important, they cannot replace direct research on humans [1–3]. However, over the last few years, much has been done to increase our knowledge of the female genital anatomy. Clarification of clitoral anatomy in particular, by dissection [4–6], immunohistochemistry [7–9], and modern imaging technologies [10–12] has led to a more accurate understanding of the clitoral neuroanatomy, physiology, and relationships between the clitoris, urethra, and distal vagina [13]. Sonographic studies have defined the dynamic clitoral complex, constituted by the root of clitoris and anterior vaginal wall during intercourse, explaining the role of the G-spot area during sexual stimulation with penetration [14]. Traditionally, information about clitoris morphology has been derived from nonphysiological data obtained by intraoperative and postmortem observations, the latter being mainly from elderly postmenopausal women [15]. Additionally, autopsy is an invasive procedure that alters the natural arrangement of the delicate erectile tissue, along with its spatial relationship to other perineal structures. Moreover, in the different phases of a woman’s life, her erectile tissue can undergo physiological changes caused by hormonal and metabolic factors. However, data on the dynamic morphology of the clitoris are scant and there is no scientific research, reported in the literature, about its functional anatomy that includes younger woman. Some clitoral anatomy studies have been performed in human fetal tissue and in healthy, premenopausal women using magnetic resonance imaging [16,17]. Postmortem examinations have demonstrated that the macroanatomy of the clitoris is quite variable. Its components include the erectile bodies and the gland clitoris. The microscopic anatomy of the clitoris is consistent among different subjects. Briefly, its histology is similar to that of the penis: it consists of cavernous tissue, encircled by a thin fibrous capsule surrounded by large nerve trunks and vessels. The cavernosal tissue is comJ Sex Med 2011;8:1675–1685
Caruso et al. posed of smooth and connective trabecular tissues, which enclose the cavernosal sinusoidal spaces [18]. Clitoral anatomy based on cadaveric studies has been limited by the lack of access to younger women, with most being from elderly, postmenopausal women in whom erectile structures were distorted by atrophy, by the absence of blood flow, and by the embalming process. The inability to objectively study this structure noninvasively and without distortion has limited research applications in fields such as female sexual dysfunction [19]. The aim of our study was to evaluate the ultrastructure of the clitoral cavernosal tissue in healthy women and those affected by metabolic pathologies, such as diabetes, and to investigate the histomorphological aspects of these “in vivo” subjects in order to understand specific age-related structural changes of the clitoris and its physiological modifications caused by hormonal and metabolic factors during different phases of a woman’s life. The fine-needle biopsy technique is a minimally invasive procedure and guarantees good tissue preservation for electron microscopy. Due to the virtual absence of complications and functional impairment, we planned a morphological study on volunteers, with the aim of comparing the normal morphology as well as the pathological alterations in the female cavernous tissue. Methods
Setting and Sample The institutional review board of our departments approved the study protocol, which conformed to the ethical guidelines of the 1975 Helsinki Declaration. All women provided informed written consent before enrollment in the study. The study was not advertised, and no remuneration was offered. Women with a history of severe hypertension, thromboembolic disorder, obesity (body mass index [BMI] >30 kg/m2), hepatic dysfunction, pregnancy within the previous 6 months, breastfeeding, tobacco use and/or drug abuse, psychotropic medications, any kind of hormonal therapy were excluded from the study. Forty-three women affected by diseases indicating surgery and general anesthesia came to our center. Informed consent was obtained directly from 38 women who were more than 18 years of age. Parental consent was obtained for five teenagers. We considered five subgroups: (i) five teenagers, aged 14–18 years (mean age 16 ⫾ 1.8) with a BMI
Ultrastructural Clitoral Cavernous Tissue of 23.1 ⫾ 3.1 kg/m2, and parity = 0; (ii) eight young premenopausal women, aged 23–32 years (mean age 27 ⫾ 2.5) with BMI of 24.3 ⫾ 3.3 kg/ m2, and mean parity 1.3; (iii) 10 premenopausal women, aged 38–47 years (mean age 43 ⫾ 3.5) with BMI of 25.2 ⫾ 3.4 kg/m2, and mean parity 2.4; (iv) nine type I diabetic premenopausal women, aged 27–43 years (mean age 34 ⫾ 3.6) with BMI of 25.3 ⫾ 3.8 kg/m2, and mean parity 2.1; and (v) 11 naturally postmenopausal women aged 51–55 years (mean age 53 ⫾ 3.2) with BMI of 25 ⫾ 2.1 kg/m2, with mean parity 3.2. All subjects underwent surgery for benign urogynecological disease: premenopausal women for dermoid cyst (four), endometriosis (eight), uterine myoma (six), uroincontinence (three), or endometrial polyps (two); diabetic premenopausal women for uterine myoma (three), uroincontinence (two), or endometrial polyps (four); natural postmenopausal women for uterine myoma (four), endometrial polyps (three), uroincontinence (four), or endometrial hypertrophy (one). The mean duration of diabetes of premenopausal women was 6.1 ⫾ 2.3 years, and the mean glycosylated hemoglobin A1c (HbA1c) value was 8.1% ⫾ 1.3%.
Instruments Each woman underwent color Doppler ultrasound to study clitoris morphology. Ultrasound was performed by the same investigator (R.M.) using a SonoAce 8800 (Medison Co., Seoul, Korea) with a 7.5-MHz linear transducer. Each woman was scanned in the gynecological position. After applying gel, the Doppler translabial probe was placed sagittally on the clitoris at an angle of
