Histological and Gene Expression Analysis of the Effects of Menopause Status and Hormone Therapy on the Vaginal Introitus and Labia Majora.

BACKGROUND: The study aimed to determine the effect of menopausal status and hormone therapy on the introitus and labia majora at the levels of histology and gene expression. METHODS: Three cohorts of 10 women each (pre-menopause, post-menopause and post-menopause + hormone therapy) were selected based on the presentation of clinical atrophy and vaginal pH. Biopsies were obtained from the introitus (fourchette) and labia majora and processed for histology and gene expression analyses with microarrays. Other data collected included self-assessed symptoms, serum estradiol, testosterone, serum hormone binding globulin and the pH of the vagina and labia majora. RESULTS: The introitus appears exquisitely sensitive to hormone status. Dramatic changes were observed in histology including a thinning of the epithelium in post-menopausal subjects with vaginal atrophy. Furthermore, there was differential expression of many genes that may contribute to tissue remodeling in the atrophic introitus. Levels of expression of genes associated with wound healing, angiogenesis, cell migration/locomotion, dermal structure, apoptosis, inflammation, epithelial cell differentiation, fatty acid, carbohydrate and steroid metabolism were significantly different in the cohort exhibiting atrophy of the introitus. While changes were also observed at the labia, that site was considerably less sensitive to hormone status. The gene expression changes observed at the introitus in this study were very similar to those reported previously in the atrophic vagina providing further evidence that these changes are associated with atrophy. CONCLUSIONS: The histological and gene expression changes occurring within the introitus after menopause may contribute to the constellation of symptoms that constitute the genitourinary syndrome of menopause.

The International Society for the Study of Women's Sexual Health Process of Care for Management of Hypoactive Sexual Desire Disorder in Women.

The International Society for the Study of Women's Sexual Health process of care (POC) for management of hypoactive sexual desire disorder (HSDD) algorithm was developed to provide evidence-based guidelines for diagnosis and treatment of HSDD in women by health care professionals. Affecting 10% of adult females, HSDD is associated with negative emotional and psychological states and medical conditions including depression. The algorithm was developed using a modified Delphi method to reach consensus among the 17 international panelists representing multiple disciplines. The POC starts with the health care professional asking about sexual concerns, focusing on issues related to low sexual desire/interest. Diagnosis includes distinguishing between generalized acquired HSDD and other forms of low sexual interest. Biopsychosocial assessment of potentially modifiable factors facilitates initiation of treatment with education, modification of potentially modifiable factors, and, if needed, additional therapeutic intervention: sex therapy, central nervous system agents, and hormonal therapy, guided in part by menopausal status. Sex therapy includes behavior therapy, cognitive behavior therapy, and mindfulness. The only central nervous system agent currently approved by the US Food and Drug Administration (FDA) for HSDD is flibanserin in premenopausal women; use of flibanserin in postmenopausal women with HSDD is supported by data but is not FDA approved. Hormonal therapy includes off-label use of testosterone in postmenopausal women with HSDD, which is supported by data but not FDA approved. The POC incorporates monitoring the progress of therapy. In conclusion, the International Society for the Study of Women's Sexual Health POC for the management of women with HSDD provides a rational, evidence-based guideline for health care professionals to manage patients with appropriate assessments and individualized treatments.

Perceptions of dyspareunia in postmenopausal women with vulvar and vaginal atrophy: findings from the REVIVE survey.

Symptoms of vulvar and vaginal atrophy (VVA), including dyspareunia and vaginal dryness, have a distinct negative impact on a woman's quality of life. The REVIVE survey highlighted the lack of awareness of VVA symptoms among postmenopausal women with vaginal symptoms, with many women reluctant to initiate discussions with their healthcare professionals despite the presence of vaginal symptoms. The REVIVE survey also provided insights into women's views of VVA treatments. Women reported displeasure with the vaginal administration route, lack of symptom relief with over-the-counter products, and concerns about the safety of estrogen therapies. With the high prevalence of VVA, obstetricians/gynecologists should become vigilant in identifying women with VVA by implementing screening and discussion of symptoms during routine office visits - providing patients with information about appropriate therapies based on the severity and impact of symptoms, keeping in mind individual preferences and perceptions.

Twice-weekly synthetic conjugated estrogens vaginal cream for the treatment of vaginal atrophy.

OBJECTIVE: The aim of this study was to evaluate low-dose synthetic conjugated estrogens A (SCE-A) cream administered twice weekly for the treatment of moderate to severe vulvovaginal atrophy (VVA) in a symptomatic postmenopausal population. METHODS: In a multicenter, double-blind, randomized, placebo-controlled study, 305 women with symptoms of VVA were treated with either 1 g SCE-A cream (n = 150) or matching placebo (n = 155) for a period of up to 12 weeks. Participants had to have a vaginal pH of greater than 5, less than or equal to 5% superficial cells on a vaginal smear, and at least one of five symptoms of VVA (dryness, soreness, irritation, pain with intercourse, and bleeding after intercourse) that was moderate or severe in intensity. Women had to select one moderate or severe symptom as the most bothersome. RESULTS: Efficacy was assessed at 2, 3, 4, 8, and 12 weeks and included the change from baseline in the severity of the most bothersome symptom (MBS), maturation index, and pH. Most women identified vaginal dryness as the MBS (48%) followed by pain with intercourse (31.3%). A statistically significant increase in the maturation index and significant decreases in pH and severity of the MBS were observed for those treated with SCE-A vaginal cream compared with placebo. CONCLUSIONS: A low dose (1 g = 0.625 mg) of SCE-A vaginal cream administered twice weekly was shown to be effective compared with placebo in treating VVA in postmenopausal women for the three coprimary efficacy measures of maturation index, pH, and severity of the MBS.

A randomized study of low-dose conjugated estrogens on sexual function and quality of life in postmenopausal women.

OBJECTIVE: To evaluate the effects of combined vaginal and oral low-dose estrogen plus progestogen therapy (EPT) on the frequency and severity of dyspareunia, sexual function, and quality of life in recently postmenopausal women. METHODS: This outpatient, double-blind, randomized, placebo-controlled trial enrolled 285 healthy, sexually active postmenopausal women aged 45 to 65 years. Women received either one daily oral low-dose conjugated estrogens (0.45 mg)/medroxyprogesterone (1.5 mg) tablet for six 28-day cycles along with 1 g conjugated estrogens vaginal cream (0.625 mg), intravaginally for the first 6 weeks of the trial or a placebo cream and placebo tablet. Efficacy was evaluated using the McCoy Female Sexuality Questionnaire, self-reported daily diary cards, the Brief Index of Sexual Functioning-Women (BISF-W), and the Women's Health Questionnaire. RESULTS: The EPT group had a significant decrease in the frequency of dyspareunia compared with baseline and placebo in an analysis of responses to the McCoy Female Sexuality Questionnaire. Also, EPT was associated with a significant improvement in a woman's level of sexual interest, frequency of orgasm, and pleasure of orgasm. There was no effect of EPT use on coital frequency. The EPT group had significant improvement in receptivity/initiation and relationship satisfaction, although not in other BISF-W domains, versus placebo (BISF-W analysis) and significant improvement versus placebo on most Women's Health Questionnaire responses. CONCLUSIONS: EPT provided a statistically significant improvement compared with placebo in dyspareunia, sexual experience, and quality of life as measured in this study. In general, EPT also improved self-reported sexual perception and enjoyment significantly compared with placebo.

Partnership issues and sexuality.

The sexual response cycle in humans usually exists within the context of a partnership. Current codification of sexual function/dysfunction has failed to incorporate the concept of satisfaction and the interpersonal relationship into the cycle and both factors are crucial to most women (and the majority of older men). Partnership issues are a critical element not only in the sexual response cycle but should be considered a major component of both female and male sexuality.

Necrotizing fasciitis in gynecologic and obstetric patients: a surgical emergency.

OBJECTIVE: We reviewed the cases of 23 patients who were admitted to the hospital with a primary diagnosis of histopathologically confirmed necrotizing fasciitis in the lower abdomen or pelvis. Rapid demise of a healthy postpartum women piqued our interest in trying to identify the early signs and symptoms that may lead to earlier diagnosis and treatment of this often fatal disease. STUDY DESIGN: A retrospective analysis of charts of all patients who were admitted to the gynecology and obstetrics services of our hospital systems with a diagnosis of necrotizing fasciitis for the past 14 years was performed. Age, comorbid factors, precipitating events, weight, symptoms and signs, microbiologic factors, radiographs, surgical therapy, and morbidity were correlated. RESULTS: Definitive operation was accomplished within 48 hours of the diagnosis of necrotizing fasciitis in all but 3 patients. Of the 17 patients who were not puerperal, 88% of the women were obese; 65% of the women were hypertensive, and 47% of the women were diabetic. Of the total 23 patients, 70% of the women complained of severe pain, and 35% of the women had radiographic diagnostics for necrotizing fasciitis ("gas"). Four patients had diverting colostomies, and 39% of the patients had flaps or synthetic grafts. Three patients died (mortality rate, 13%). One patient who was puerperal died of a severe rapid septicemia; the 2 late deaths were the result of systemic candidiasis. CONCLUSION: Necrotizing fasciitis is a rapidly progressive, often lethal, infectious disease process that requires early aggressive debridement. Any patient with inordinate pain and unilateral edema in the pelvis, especially in the puerperium, should be suspected of having this disease. Radiographic studies are often diagnostic of this condition. The triad of pelvic pain, edema, and any sign of septicemia carries an extremely grave prognosis and mandates immediate surgical intervention.

Female sexual dysfunction.

Happiness is an attitude, not an event! The glass is either half-full or half-empty; it simply depends on the viewer. Some rich people are miserable...some poor people are ecstatic. You cannot change the world but you can change yourself. You, and you alone, control your destiny. With very little practice, you can learn to think positively. Postmenopausal estrogen deficiency leads to urogenital atrophy. Sexual dysfunction and urinary dysfunction are the most inevitable but least publicized consequences of estrogen deficiency, and these represent important quality-of-life issues that patients and health care providers are often reluctant to discuss. In addition to estrogen deficiency, oophorectomized women may be subject to androgen deficiency and problems with libido. While the relationship with one's partner is the quintessential factor in female sexuality, hormone deficiency remains important, especially in reference to genital atrophy. Humans are the products of learned behavior. We literally become what we think. "I am sick and tired" becomes a self-fulfilling prophecy. Self-esteem represents learned behavior just as ego does...but there is a world of difference between the two. Sexuality is enhanced by good self-esteem and hindered by ego: two partners working together can reach far greater heights than either alone ever imagined...one and one can equal three! There are good data to substantiate that happy people have more sex and that people who have more sex are happier. Partners need to learn to honor one another, communicate in a positive manner, develop touching salutations, be a spouse at home, and make their bedroom a sacred sanctuary. With a little behavior modification and hormone therapy, sexuality can remain a priority ad infinitum.

Quality of life and menopause: the role of estrogen.

The use of estrogen or hormone replacement therapy (ERT/HRT) in preventing disease in menopausal women has been well documented. Less attention has been paid to the menopausal symptoms that can impair the quality of life of menopausal women, such as hot flushes, sleep disorders, sexual dysfunction, and alterations in mood. Researchers have used a variety of methods to investigate these concerns. Decreases in ovarian hormones that occur with menopause have been implicated in these symptoms. Ovarian hormones affect the central nervous system and urogenital tissues directly via receptors for estrogen, progesterone, and androgens. Changes in the symptoms of menopause consequential to estrogen therapy reflect the effect of this therapy on these tissues. Evidence supporting the effectiveness of ERT/HRT in the treatment of symptoms affecting quality of life is growing and supports the use of ERT/HRT during menopause. Because the most dramatic hormonal changes associated with menopause are related to estrogen and because estrogen is usually coadministered with a progestogen in patients with an intact uterus, this review is focused primarily on ERT/HRT. Because androgen therapy may also improve quality of life by enhancing perimenopausal and postmenopausal sexual desire, function, and general well-being, a brief discussion of androgen supplementation of ERT/HRT is also included. The ideal doses and combinations of hormones must be determined on an individual basis, taking into consideration benefits, risks, and interactions of the different hormone therapies.