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Release of oxytocin and prostaglandin f(2alpha) around teasing, natural service and associated events in the mare.

Mating has been shown in many species to provoke the release of oxytocin (OT). In our study, various stimuli were applied to mares to study release of OT and prostaglandin F(2alpha) (PGF(2alpha)) associated with mating. Blood samples were collected from mares around the time of teasing both in oestrus and dioestrus and at mating. For comparison, blood samples were also collected at the time of manual manipulation of the genital tract and after intrauterine infusion of 500 ml phosphate buffered saline (PBS). Additional samples were collected 16 to 18 h after mating. Mating caused a significant increase in OT in all mares and teasing caused a significant OT response in 6 of 10 oestrous and 3 of 5 dioestrous mares. However, mating and teasing had no significant effect on concentrations of 15-keto-13,14-dihydro-PGF(2alpha) (PGFM). Manual manipulation of the clitoris, vagina and cervix caused significant OT release in all mares and intrauterine infusion of 500 ml PBS caused significant OT release in three of the five mares. However, only one mare had a significant PGF(2alpha) response during manual manipulation and only one responded positively to intrauterine infusion of 500 ml PBS. We concluded that events around mating, including stimulation of the genital tract and uterine distension, often caused an increase in circulating concentrations of OT but only rarely in PGFM.

Animals↗

Intraoperative monitoring of the bulbocavernosus reflex: the method and its problems.

OBJECTIVES: This study evaluates the method of intraoperative neurophysiological monitoring of the bulbocavemosus reflex (BCR) with reference to stimulation and detection. METHODS: The study was performed on a group of 65 patients, 53 men and 12 women, who underwent surgery for lower thoracic and lumbar spinal trauma, with no neurological deficit prior to or following surgery. Stimulating electrodes were placed on the dorsum of the penis or the clitoris. Single and double stimuli were used, as well as trains of 3, 4 and 5 stimuli. Detecting wire electrodes were introduced into the perianal region. RESULTS: A single stimulus elicited the BCR in 50%, pairs in 75%, trains of 3 in 95%, and trains of 4 and 5 in 100% of patients. With placement of the detecting electrodes 2.5 cm deep to the skin, the BCR was detected in 13% of hemisphincters in women, and in 81% of hemisphincters in men. With controlled intramuscular placement of detecting electrodes, the BCR was detected in 97% of hemisphincters in men. With bifocal detection the BCR amplitudes were 30-312 mV (median 90), and interside amplitude ratio was 0.05-1 (median 0.66); with monofocal detection, amplitudes and interside amplitude ratio were 30-560 mV (median 200) and 0.15-1 (median 0.86), respectively. CONCLUSIONS: A train of 4 electrical stimuli is optimal in eliciting the BCR in anesthetized patients. The low rate of elicitability in women was most probably due to inefficient stimulation. Detection was improved by controlled intramuscular placement of electrodes. Monofocal detection yielded higher BCR amplitudes. Interside difference and interindividual variability of the BCR amplitude were considerable.

Adolescent↗

Nitrergic neurotransmission mediates the non-adrenergic non-cholinergic responses in the clitoral corpus cavernosum of the rabbit.

The corpus cavernosum is the erectile tissue in the penis and clitoris. Although nitrergic neurotransmission has been characterized in detail in the penile corpus cavernosum, functional studies on the inhibitory non-adrenergic non-cholinergic (NANC) transmission in the clitoral corpus cavernosum have been lacking. Here we demonstrate that electrical field stimulation (EFS) induces NANC relaxation responses in the clitoral corpus cavernosum of the rabbit. These responses were inhibited by NG-nitro-L-arginine methylester (L-NAME), 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ) or tetrodotoxin. The inhibitory effect of L-NAME was partially reversed by L-arginine but not by D-arginine. EFS-induced relaxations were enhanced by an inhibitor of type V cyclic GMP phosphodiesterase, zaprinast. These results suggest that nitrergic neurotransmission is responsible for the NANC relaxation responses in the clitoral corpus cavernosum of the rabbit.

Animals↗

Decreased circulating levels of estrogen alter vaginal and clitoral blood flow and structure in the rabbit.

Aging and menopause related decline in circulating levels of estrogen has been shown to adversely affect female sexual arousal function. Our aim was to study the effects of circulating levels of estrogen on the hemodynamic mechanism of vaginal and clitoral engorgement and on the structure of the vaginal and clitoral cavernosal tissue in the rabbit. New Zealand White female rabbits (3.5-4 kg) were randomly divided into three groups with five rabbits in each group: control; bilateral oophorectomy; bilateral oophorectomy undergoing subcutaneous injection of estrogen (40 microg/kg/day). After 6 weeks, the serum levels of 17 beta-estradiol were measured and systemic blood pressure was monitored. Vaginal and clitoral cavernosal blood flows were measured with laser Doppler flowmeter before and after pelvic nerve stimulation. Cross sections of the clitoris and vagina were processed for histologic examination and histomorphometric image analysis. Serum level of 17 beta-estradiol (pg/ml; mean+/-s.d.) revealed a significant decrease in the oophorectomy group (25.4+/-5.1) compared with the control (38.5+/-7.6) and estrogen replacement (115.9+/-57.3) groups (P<0.05). Nerve stimulation-induced peak vaginal and clitoral intracavernosal blood flows in the oophorectomy group (28.9+/-16.3 and 6.1+/-1.4, respectively) were significantly less than those recorded in the control (48.9+/-6.5 and 11.0+/-2.4, respectively) or estrogen replacement (48.7+/-12.2 and 10.1+/-2.8, respectively) group (P<0.05). In histology, marked thinning of the vaginal epithelial layers, decreased vaginal submucosal microvasculature, and diffuse clitoral cavernosal fibrosis were evident in the oophorectomy group but not in the estrogen supplement and control groups. In histomorphometry, the percentage of clitoral cavernosal smooth muscle in the oophorectomy group (49.6+/-6.2) was significantly decreased compared with the control (56.8+/-2.6) and estrogen replacement (58+/-3.0) groups (P<0.05). Our studies show that decline in circulating levels of estrogen impairs the hemodynamic mechanism of vaginal and clitoral engorgement and leads to histopathologic changes in the vagina and clitoral cavernosal tissue. These observations suggest that decreased circulating levels of estrogen, a physiologic change in the menopausal state, may play a role in the development of female sexual arousal dysfunction.

Animals↗

Response of the internal reproductive organs to clitoral stimulation: the clitorouterine reflex.

We investigated hypothesis that uterine erection, elevation and enlargement during sexual response are reflex and result from penis buffeting the glans clitoris (GC). In 23 healthy women, two recording electrodes were applied to the uterine mucosa and one to cervix uteri (CU). GC was stimulated electrically and mechanically by pencil electrode. The uterine and CU pressures were measured. Tests were repeated after anesthetization of the uterus or GC. Uterine electrodes recorded slow waves, followed by random bursts of action potentials (APs). No waves registered from CU. Electrical or mechanical GC stimulation eliminated uterine electric waves, but anesthetized GC did not, nor did GC stimulation while the uterus anesthetized. Uterine pressure declined on electrical or mechanical stimulation. Results suggest presence of reproducible reflex relationship between GC and the uterus, we call 'clitorouterine reflex'. GC buffeting seems to evoke reflex and initiate uterine responses. Reflex may prove of diagnostic significance in sexual disorders.

Adult↗

VIP, vagina, clitoral and periurethral glans--an update on human female genital arousal.

The sexually quiescent human vagina is a just moist, potential space with a minimal blood flow and very low luminal oxygen tension. The first measurable sign of sexual arousal is an increase in the blood flow. This creates the engorged condition, elevates the luminal oxygen tension and stimulates the production of surface vaginal fluid by an increased plasma transudation that saturates the fluid reabsorptive capacity of the epithelium. The vaginal lubrication created allows painless penile penetration and coital movements. The mechanisms underlying the changes appear to be mediated by Vasoactive Intestinal Peptide (VIP). VIP is present in nerves closely applied to blood vessels in the vaginal wall. Administration of VIP either intravenously, or by subepithelial injection in the vaginal wall, increases vaginal blood flow and induces vaginal fluid production. Increases in vaginal blood flow by sexual arousal are not blocked by atropine injection indicating that cholinergic mechanisms are unimportant. All the present evidence suggests that the local vaginal release of VIP induces the vaginal changes of arousal. Discourse on vaginal and pudendal anatomy (Sevely, 1987) has proposed that the female glans of the clitoris is not the true homologue of the penile glans because it has no urethral opening. The speculative suggestion is that the true female glans is the area surrounding the urethral opening (which has no specific anatomical name). Preliminary studies indicate that the area of this tissue (periurethral glans) decreases on vaginal penile insertion and reappears on withdrawal indicating that it is moved during coitus. How important such movement is to stimulate erotic sensation and how sensitive this area is to erotic stimulation are unanswered questions.

Clitoris↗

Feminizing genital reconstruction: experience with 52 cases of ambiguous genitalia.

AIM: The last decade witnessed the introduction of different modifications and even new techniques for feminizing genitoplasty. The claim was that the classical Hendren's procedure was associated with unsatisfactory results. At the King Khalid University Hospital, the Hendren's operation was the procedure of choice for feminizing genitoplasty. In this report, we describe our experience with a total of fifty-two cases of ambiguous genitalia. We understand that this comes in the midst of growing criticism of the Hendren's procedure. MATERIALS AND METHODS: The medical records of 52 consecutive patients with ambiguous genitalia who underwent feminizing genital reconstruction were reviewed. Forty-five patients (86.5%) had congenital adrenal hyperplasia (CAH), 3 patients had testicular feminization syndrome, 2 patients had mixed gonadal dysgenesis, one patient had vaginal atresia with Kaufman's syndrome and one patient had isolated congenital clitoromegaly. Age at first presentation ranged between 1 day to 15 years. Feminizing genital reconstruction using Hendren's technique was carried out as a single stage procedure in 29 (55.81%) patients and as staged surgery in 23 (44.2%) patients. A total of 50 clitoral operations and 43 vaginoplasties were performed. Follow-up ranged from 6 months to 12 years (mean 3 and 1/2 years). The surgical results were analyzed and complications documented. RESULTS: Reconstruction was completed in 47 (90.2%) patients. Thirty-six (78.2%) patients had a satisfactory genital appearance with normal looking clitoris. Seven patients required revision clitoroplasty. Thirty-six (83.7%) patients had a good size vagina appropriate for age. Seven patients (16.2%) had vaginal stenosis and two had revision vaginoplasty with good results. Postoperative complications included urethral fistula (one patient), meatal stenosis (one patient), and transient neurogenic bladder (one patient). The final cosmetic results were considered excellent in 40 (85.1%), fair in 4 patients, and poor in 3 patients. CONCLUSION: The Hendren's techniques of flap vaginoplasty for low confluence and vaginal pull-through for high confluence offer satisfactory cosmetic and functional results. Long-term follow-up is necessary to ensure social and psychosexual adjustment.

Adolescent↗

Feminising genitoplasty: one-stage genital reconstruction in congenital adrenal hyperplasia: 30 years' experience.

The study objective is to evaluate the results of our surgical technique for children with congenital adrenal hyperplasia and ambiguous genitalia at the University Hospital of Heidelberg, Department of Paediatric Surgery. The records of 19 patients with congenital adrenal hyperplasia treated between 1972 and 2004 were reviewed with respect to age at surgery, operative procedures and outcome. We describe the recession clitoroplasty technique currently used in our hospital and highlight the importance of short and long-term follow-up results with respect to appearance, position and size of the clitoris and quality of the vagina. One-stage recession clitoroplasty and vaginoplasty gives very satisfactory cosmetic and functional results, with few complications and a reduced need for secondary surgical interventions. The results of this study support the assumption that total correction can be achieved through a single-stage operation, performed in infancy.

Adrenal Hyperplasia, Congenital↗

[Correction of AGS-genital in severe forms of virilism (Prader III-V) (author's transl)].

An operative procedure for the correction of virilised genitalia in girls suffering from adreno-genital syndrome is reported. The existing tissues are preserved and utilised as far as possible to reconstruct a vaginal opening. The dorsal and ventral scillae and nerve supply of the glans clitoris are preserved while the corpora cavernosa are resected.

Adrenal Hyperplasia, Congenital↗

Epidermal clitoral inclusion cyst after type I female genital mutilation.

OBJECTIVE: To document the occurrence of long-term sequelae after type I female genital mutilation (FGM) and describe the surgical treatment of epidermal clitoral inclusion cyst. STUDY DESIGN: Twenty-one women presented with epidermal clitoral inclusion cyst after type I FGM at the Department of Obstetrics and Gynecology at King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia. The duration (mean +/- SD, range) of symptoms was 10.3 +/- 5.4, 2 to 20 years. They were treated by excision of the cyst with particular attention to preserve the remaining part of the clitoris. The technique involves making a vertical incision in the skin, dissecting and excising the cyst, removing the excessive skin, and reapproximating the skin edges. RESULTS: The procedure was done on all patients without intraoperative complications. All except one were discharged home on the second postoperative day. Follow-up showed no recurrence of symptoms. CONCLUSION: Long-term sequelae can occur after type I FGM. The surgical treatment of clitoral inclusion cyst is simple and effective.

Adolescent↗

Neurophysiology and pharmacology of female genital sexual response.

Vaginal sexual arousal is a vasocongestive and neuromuscular event controlled by facilitatory parasympathetic and inhibitory sympathetic inputs. Autonomic preganglionic parasympathetic and inhibitory sympathetic fibers to the vagina and clitoris originate in the spinal cord in the sacral parasympathetic nucleus at the sacral level and in the dorsal gray commissure and the intermediolateral cell column at the thoracolumbar level, respectively. Parasympathetic fibers are conveyed by the pelvic nerve, and sympathetic fibers are conveyed by the hypogastric nerve and the paravertebral sympathetic chain. The activity of these spinal nuclei is controlled by descending projections from the brain and sensory afferens (conveyed in the pudendal, hypogastric, pelvic, and vagus nerves) from the genitalia. A key but unresolved issue concerns the neurotransmitters involved in the control of genital sexual arousal. At the peripheral level, acetylcholine plays a minor role in the regulation of vaginal blood flow, however, recent data suggests that it may be involved in the control of vaginal smooth muscle contractions. Vasoactive intestinal peptide and nitric oxide may be responsible for the increase in vaginal blood flow during sexual arousal, whereas noradrenaline is likely inhibitory. Within the central nervous system, serotoninergic projections from the brain to the spinal cord likely inhibit the induction of genital arousal by peripheral informations (spinal reflex). Although some neurotransmitters regulating the display of sexual behavior have been identified (for example, dopamine), their involvement in the control of genital sexual arousal has not been invested. Anatomical and electrophysiological data point to a contribution of the paraventricular nucleus of he hypothalamus and the median preoptic area, respectively, as key elements in the control of genital arousal. The recent development of models allowing the assessment of vaginal sexual arousal in anesthetized female rats should assist in deciphering the neurochemical pathways controlling vaginal sexual arousal and the development of suitable pharmacological treatment for female sexual dysfunctions.

Acetylcholine↗

Dyspareunia.

Dyspareunia--painful intercourse--is a common cause of sexual difficulty. The following paper discusses, for both males and females, the common causes of dyspareunia and in many instances the appropriate treatment. Painful intercourse for the male is related either to the prepuce, glans penis, penile shaft, testicles, or urethra and prostate gland, whereas painful intercourse for the female is related to the vaginal opening, clitoris, vagina, or uterus, tubes, and/or ovaries. Each of the above is discussed.

Bacterial Infections↗

Influence of androgens on the genital tract of cyclic heifers.

Cyclic heifers were implanted with the synthetic androgen trenbolone acetate (TBA = 17 beta-hydroxy-19-norandrosta-4, 9, 11-trien-3-on-17 beta-acetate, C2OH2403) (for formulas see Fig. 1). The influence of this androgen on the macroscopic and microscopic morphology of the genital tract was studied. The most striking result was the induction of polycystic ovaries. The clitoris was markedly enlarged and the cervix showed an increased amount of mucus. Microscopically, extensive folding of the cervical epithelium, consisting of tall swollen columnar cells with basal nuclei was seen. The vagina showed an increase of PAS-positive granules in the superficial layer of the epithelium, while there was no increase in the height of the epithelium. These effects are due to androgenic influence on the female genital tract and are in no case specific to one particular product. They could be of help in the detection of the illegal use of agents with androgenic activity.

Androgens↗

Clitoral hemodynamic changes after a topical application of alprostadil.

We performed duplex ultrasonography of the clitoris to assess the local hemodynamic changes after a topical application of alprostadil. Color duplex ultrasonography was used to evaluate 18 women before and after the application of 1 g of 0.2% alprostadil gel. The peak systolic velocity and end diastolic velocity showed a statistically significant difference after the application. All women showed labial and clitoral engorgement, 72% reported a pleasant sensation of warmth, and no systemic side effects were found. These findings are similar to the values reported after sexual stimulation, indicating that topical vasoactive drugs might help in the differential diagnosis of the vascular component of female sexual dysfunction.

Administration, Topical↗

Hemodynamic evaluation of the female sexual arousal response in an animal model.

The goal of this study was to assess the utility of existing and new techniques for characterizing and measuring hemodynamic changes in the vagina and clitoris in response to pelvic nerve stimulation (PNS) in an animal model. Using female New Zealand White rabbits, we measured the following parameters before, during, and after PNS at 4, 16, and 32 hertz (Hz): clitoral hemoglobin (Hb) content by laser oximetry, clitoral blood flow by laser Doppler flowmetry, vaginal luminal pressure of upper and lower segments, and clitoral intracavernosal pressure. Clitoral tissue concentrations of total and oxygenated hemoglobin (oxy-Hb) increased in a frequency-dependent manner while deoxygenated hemoglobin (deoxy-Hb) concentration decreased. The duration of the responses at 16 and 32 Hz were significantly greater than at 4 Hz. Clitoral blood flow increased significantly only at 32 Hz with a prolonged response duration, relative to 4 Hz. PNS caused vaginal luminal pressure changes that were highly variable, but qualitatively different, between the upper and lower regions. Clitoral intracavernosal pressure did not change significantly in response to PNS. Measurement of changes in tissue Hb content by the novel technique of laser oximetry provides a direct assessment of blood flow in a noninvasive manner and may prove to be a powerful tool in evaluating hemodynamic aspects of the female genital sexual response.

Animals↗

A new non-pharmacological vacuum therapy for female sexual dysfunction.

Although Female Sexual Dysfunction (FSD) affects 40% of American women, there is no FDA-approved pharmaceutical therapy. The EROS-CTD (Clitoral Therapy Device, UroMetrics, Inc., St. Paul, MN) treatment is the first FDA cleared-to-market therapy for FSD. Clitoral engorgement is believed to play an important role in female sexual arousal and overall sexual satisfaction. The EROS-CTD is a small, battery-powered device designed to enhance clitoral engorgement, increase blood flow to the clitoris, and ultimately improve arousal in women with FSD. The objective of this study was to assess the effectiveness of the EROS-CTD on sexual arousal (genital sensation, vaginal lubrication, ability to reach orgasm, and sexual satisfaction) in normal volunteers and women with FSD.

Adult↗

Testis-like steroidogenesis in the ovotestis of the European mole, Talpa europaea.

The female European mole (Talpa europaea) presents a vivid paradox in relation to our contemporary understanding of mammalian sexual differentiation. These animals are exceptional among female mammals in that they possess bilateral ovotestes. The ovotestis contains a morphologically normal ovarian component that develops during the spring breeding season and a histologically defined testicular region, the interstitial gland, which enlarges during autumn when the ovarian component decreases in size. In correlation with this unusual gonadal situation, the female mole displays a penile clitoris traversed by a urethral canal. Although the histology of the ovotestis is well documented and has recently been extended to an additional three species of the genus Talpa, there have been no clear indications of the physiological function, particularly androgen production, of the ovotestis in these female moles. This paper presents the first clear evidence of seasonal variation in plasma testosterone concentrations, which parallel the growth and regression of the "testicular" interstitial gland, in T. europaea. Plasma androstenedione did not show significant seasonal variation, but plasma testosterone (1.06 +/- 0.2 ng/ml) and gonadal testosterone concentration (1.57 +/- 0.65 microgram/mg protein) in females in autumn were significantly higher (p < 0.02) than plasma (0.4 +/- 0.2 ng/ml) and gonadal (0.24 +/- 0.21 microgram/mg) concentrations in pregnant or immediately postpartum females in spring. Our data also reveal selective metabolic production of testosterone from radiolabeled steroid precursors (progesterone and androstenedione) by these ovarian interstitial tissues and male testes; estradiol is produced by ovarian tissue but not interstitial gland or testis.

Androstenedione↗

Transient masculinization in the fossa, Cryptoprocta ferox (Carnivora, Viverridae).

In at least 9 mammalian species, females are masculinized throughout life, but the benefits of this remain unclear despite decades of thorough study, in particular of the spotted hyaena (Crocuta crocuta) in which the phenomenon has been associated with a high fitness cost. Through examination of wild and captive fossas (Cryptoprocta ferox, Viverridae), androgen assays, and DNA typing for confirmation of gender, we made the first discovery of transient masculinization of a female mammal. Juvenile female fossas exhibited an enlarged, spinescent clitoris supported by an os clitoridis and a pigmented secretion on the underpart fur that in adults was confined to males. These features appeared to diminish with age. The majority of adult females lacked them, and os clitoridis length was inversely related to head-body length. No evidence was found to link this masculinization to elevated female androgen levels. Circulating concentrations of testosterone and androstenedione, but not dihydrotestosterone, were significantly lower in females than in males. No significant differences in testosterone, androstenedione, or dihydrotestosterone levels were found between juvenile (masculinized) and adult (nonmasculinized) females. There are several possible physiological mechanisms for this masculinization. None of the hypotheses so far proposed to explain the evolutionary basis of female masculinization in mammals are applicable to our findings. We present 2 new hypotheses for testing and development.

Aging↗