and Filippo Murina2
(1)
Center of Gynecology and Medical Sexology, San Raffaele Resnati Hospital, Milan, Italy
(2)
Lower Genital Tract Disease Unit V. Buzzi Hospital, University of Milan, Milan, Italy
Women have a much longer life expectancy than men: around 80–85 years of age in the high-income countries. This means 30–35 years after the menopause. This translates into an incredible gain in life duration (30 years on average) in comparison to only 100 years ago, when the mean life expectancy for women, in Western Europe for example, was 48 years.
Life expectancy is not enough. Women would love to have a more appealing and longer health expectancy (HE). A longer, and hopefully happy, sexual life is part of the dream. Menopause, ongoing diseases, and a pathologic aging are the first enemies of the pursuit of a longer HE, with specific and rapid negative effects on the sexual function.
8.1 Postmenopausal Genital, Vaginal, Vulvar, Urinary, and Sexual Aging: The “Renaming” Problems
Soon after the menopause the disappearance of the ovarian sex hormones threatens the basic roots of genital arousal, dramatically affecting the anatomy and function of women’s genital organs, vulvar and vaginal aging leading the list (Graziottin and Gambini 2015; Graziottin 2015a).
Vulvovaginal aging causes tissues’ involution, named vulvovaginal atrophy (VVA). This causes a constellation of symptoms that include vaginal dryness and dyspareunia, the most frequently reported; vulvar and vaginal irritation; burning and itching (Phillips et al. 2015); soreness; vaginal discharge; postcoital bleeding; and postcoital cystitis (Graziottin 2014; Graziottin and Zanello 2015), just to mention the most bothersome (Graziottin et al. 2015; Graziottin and Lukasiewicz 2016).
All these symptoms are reported after a natural menopause and, with a more invalidating impact, after premature menopause (Graziottin and Lukasiewicz 2015), more so if associated with oncologic surgery and treatments (Graziottin and Lukasiewicz 2016).
The term VVA has been recently modified in Genitourinary Syndrome of the Menopause (GSM) (Portman and Gass 2014) (Box 8.1), more inclusive of the comorbid urinary symptoms. Women may present with some or all the signs and symptoms. However, most of the published literature is still using the VVA definition (Freedman 2009; Nappi and Kokot-Kierepa 2012; Nappi et al. 2013; Nappi and Palacios 2014; Parish et al. 2013). VVA can be definitely considered the vulvovaginal component of GSM (Genitourinary Syndrome of the Menopause). Therefore both terms will be used here.
Box 8.1. The Genitourinary Syndrome of the Menopause (GSM)
It includes:
Genital symptoms: vulvovaginal atrophy, vulvar burning, vulvar itching, soreness, and vaginal discharge
Sexual symptoms: vaginal dryness, genital arousal difficulties, dyspareunia (painful intercourse), and postcoital bleeding
Urinary symptoms: urgency, frequency, urinary incontinence, and recurrent cystitis
The same classification problems hold true for coital pain. While dyspareunia translates easily into “painful intercourse” in the clinical setting, classification difficulties make definitions very complex and still under debate. The same pathophysiology of dyspareunia is discussed. Dyspareunia has been now renamed genito-pelvic pain penetration disorder (GPPPD) in DSM V (2015), with critical aspect in differential diagnosis between vaginismus and dyspareunia still unresolved (Lahaie et al. 2015; Reissing et al. 2014).
For example, in every woman the clinician should assess how much of the coital pain depends on:
The vulva (and specifically here from the vulvar aging after the menopause)
The vestibular mucosa changes or frank inflammation (postmenopausal vulvar vestibulitis (VV) or provoked vestibulodynia (PVD)
The vaginal dryness and aging
The hyperactive pelvic floor
An inadequate processing of painful stimuli potentiated by fear in a subset of women
Of note, the neuropathic vulvar pain labeled as “provoked vestibulodynia” and “vulvodynia” is not limited to younger women (although it certainly peaks around the 30 years of age) but can affect as well the postmenopausal women.
A recent very accurate paper of Philips et al. (2015), aimed at describing similarities and differences in symptoms of PVD in pre- and postmenopausal women, indicate that postmenopausal women reported significantly more vulvar burning (70.00 % vs 43.42 %, P = 0.03), but there were no differences in vulvar itching (20.00 % vs 22.37 %, P = 0.82), vulvar stinging (40.00 % vs 36.84 %, P = 0.79), vulvar aching (50.00 % vs 63.16 %, P = 0.28), and vulvar stabbing (60.00 % vs 71.06 % P = 0.34) or in mean number of symptoms (2.40 ± 1.0 vs 2.37 ± 1.4, P = 0.92). In conclusion, pre- and postmenopausal women with PVD have similar pain scores and with the exception of a higher incidence of burning vulvar pain in postmenopausal women and similar presenting clinical symptoms.
Pain is therefore one of the leading and often neglected symptoms of the menopausal genital, vulvar, and sexual aging. This chapter will focus specifically on vulvar pain after the menopause and related genital and sexual symptom, considering VVA a part of GSM. The term dyspareunia or coital pain will be preferred, with the most recent acronym GPPPD used in brackets. Given this complexity, the Authors accept the challenge of trying to give a systematic perspective within the limits of a very magmatic classification and the persisting uncertainties from the clinical and pathophysiologic point of view.
Falling estrogen and testosterone levels after the menopause may trigger different types of vulvar pain and introital dyspareunia or genito-pelvic pain penetration disorders (GPPPD), according to different anatomic, functional, and clinical pictures, that can partly overlap. Besides aging:
Candida infections may re-exacerbate PVD, in women who suffered from it in the fertile age.
Papillomavirus infections may contribute to the oncogenic process leading to vulvar cancer and pain (Alkatout et al. 2015).
Leading etiologies of vulvar pain after the menopause are summarized in Box 8.2, where different potential contributors are “polarized” for the sake of clarity. In the clinical setting, they can be comorbid and need to be carefully diagnosed to be properly addressed.
Box 8.2. Leading Etiologies of Vulvar Pain After the Menopause
Etiologies of vulvar pain include:
- 1.
The VVA, with the associated anatomic and functional changes that lead to a progressive increasing thinning of the vestibular mucosa and vulvar skin, reduced lubrication, increased pH, altered vaginal and vulvar microbiota, and increased vulnerability to microabrasions and introital pain (dyspareunia, GPPPD), with secondary reflexive contraction of the levator ani.
- 2.
The vestibular pain (PVD), histologically more similar to the picture demonstrated in the PVD of the younger cohort, with a prominent inflammatory (mast cell dominated) tissue finding. The development of a subtype of menopausal vestibulodynia can explain the number of cases of postmenopausal coital pain. We hypothesize that the vestibule is more sensitive to withdrawal of estrogen during menopause and develops the features of vestibulodynia alongside visual changes of atrophy, at least in a subset of vulnerable patients. The vagina can also develop marked atrophy but does not become tender to the same degree as the vestibule because it has a different innervation.
- 3.
The vulvar/vestibular pain that can be associated with a more prominent vulvar dermatoses, like lichen sclerosus, which contributes to the narrowing of the vaginal introitus and introital dyspareunia.
- 4.
Vulvar cancer, HPV or not HPV associated, can cause/contribute to vulvar pain.
- 5.
Iatrogenic vulvar pain after vulvar, anal, or bladder surgery and radio/laser therapy.
- 6.
Post-traumatic vulvar pain, unintentional and intentional (sexual abuse).
In the real life these pictures can partly overlap.
8.2 Impact of Estrogens’ and Androgens’ Loss on Genital and Vulvar Trophism
Hot flashes are the most commonly identified hallmark of menopause and aging. However, many women also suffer with a constellation of vulvovaginal symptoms as a result of lowered estrogen and androgens (Graziottin and Lukasiewicz 2015). They are the tip of the iceberg of an underlying progressive genital involution leading to VVA, GSM, and vulvar pain. Genital menopausal and urinary symptoms become rapidly prominent in the majority of women, because the urogenital epithelium is particularly vulnerable to hormonal changes, unless an appropriate hormonal menopause therapy, at least topical, is performed. The characteristic vulvovaginal changes that occur during and after the menopause are due to the combination of pathophysiologic aging, hypoestrogenism, and hypoandrogenism (Graziottin and Gambini 2015).
Estradiol, the primary form of estrogen produced by a woman’s ovary during her reproductive years, plays an essential role in maintaining the elasticity and health of the genital tissues, including an appropriate vaginal and vulvar microbiota and an adequate low vaginal pH (Graziottin and Zanello 2015) The genital involution is more rapid and anticipated in women affected by a premature ovarian insufficiency (Graziottin and Lukasiewicz 2015). An iatrogenic menopause after gynecologic cancers may have an even more dramatic impact on anatomy and function of genital organs, when the premature or anticipated menopause is complicated with the side effects of vaginal/pelvic radiotherapy (Lukasiewicz and Graziottin 2015; Graziottin and Lukasiewicz 2016).
Testosterone is responsible for the hormone-dependent involution of the cavernosal bodies (clitoral, bulbocavernous, and part of the equivalent of the male corpus spongiosum, around the urethra), of the androgen-dependent cells of the skin, of the connective tissue (fibroblasts and myocells), and of the androgen-dependent nitrergic nerve fibers, present at vaginal (1/3 nitrergic, 2/3 vipergic) and vulvar level (Graziottin and Gambini 2015).
8.3 Postmenopausal Dyspareunia
Dyspareunia, genital pain associated with sexual intercourse, is a common symptom in postmenopausal sexually active women. It can adversely affect their sexual quality of life or intensify preexisting sexual disorders (Schneidewind-Skibbe et al. 2008):
Approximately 40 % of postmenopausal women report dyspareunia.
Fifty-two percent of women 50–79 years of age have been sexually active with a partner in the past year.
Twenty-two percent of married women, 70–79 years of age, report that they still have sexual intercourse.
8.4 VVA: The Three Enemies of Vulvovaginal Health in the Clinical Setting
Three major problems impair the appropriate diagnosis and treatment of VVA (Graziottin 2015a), including vulvar pain: symptoms caused by VVA are underreported, underdiagnosed, and undertreated.
8.4.1 Underreported
Embarrassment, related to the intimacy of the complaints, holds women back to seek professional advice. However, in the VIVA survey among 3520 postmenopausal women, 53 % of participants said that they would feel comfortable discussing “vaginal” discomfort with their doctor (of note, many women call “vagina” the vulva!), while 37 % would not raise the subject or hesitate to do so (Nappi and Kokot-Kierepa 2012). A third would not even tell their partner (Nappi et al. 2013).
A pervading collusion of silence that translates into a substantial diagnostic neglect is preventing effective communication, both in the high- and low-income world. In addition, general ignorance about the condition also plays a major role in the underreporting, with only 4 % of women attributing their symptoms to vulvovaginal atrophy and 63 % failing to recognize vulvovaginal atrophy as a chronic condition that requires ongoing treatment of the underlying cause (Nappi and Kokot-Kierepa 2012).
Few women attributed symptoms to menopause (24 %) or hormonal changes (12 %) (Kingsberg et al. 2013). Many women expect their doctor to start the discussion about postmenopausal vaginal health, but 50 % of the total survey population claimed that their doctor had not raised the subject (Nappi and Kokot-Kierepa 2012). Even less women think that the vulva “could age,” because of the menopause. They usually report symptoms only when vulvar itching and scratching (usually associated with lichen sclerosus) become a problem.
8.4.2 Underdiagnosed
Vulvovaginal atrophy is also called atrophic vaginitis. This wording is accurate as the increase of inflammatory molecules in the vagina, particularly IL-1 and IL-8, is the leading feature of this organ after menopause, without hormone therapy. It parallels the increase of vaginal pH and the decrease of lactobacilli. It is a chronic, progressive condition that results from the decrease in estrogen levels in the vagina that commonly occurs after the menopause.
The diagnosis of VVA is commonly based on a combination of symptoms, gynecological history and clinical findings of vulvovaginal atrophy during examination (atrophy of the introitus and labia, disappearance of the rugae, and a dry, thin, friable mucosa which can be reddened or paled with petechiae), sometimes supported by pH testing (pH > 5) and the Vaginal Maturation Index (e.g., <5 % superficial cells) (MacBride et al. 2010). It is a clinical diagnosis, but requires the doctor to have an interest in the vaginal and vulvar health of the patients with 40 % of patients expecting the doctor to initiate the discussion (Kingsberg et al. 2013). It is estimated that between 69 (Gass et al. 2011) and 98 % (Freedman 2009) of postmenopausal women have signs of vulvovaginal atrophy, with worsening features with increasing age after the menopause. More than 70 % of men note that their partner avoided sexual intimacy because of vaginal discomfort (Nappi et al. 2013)
Despite the impact on quality of life and relationships, the fact that 62 % of women complain of moderate or severe symptoms and 55 % had the symptoms for 3 or more years (Nappi and Kokot-Kierepa 2012), vulvar and vaginal atrophy remains an underreported, underdiagnosed, and therefore also an undertreated condition (Parish et al. 2013) for a number of different reasons. The figures are constant worldwide. It is estimated that 10–40 % of postmenopausal women experience discomfort due to a vulvovaginal atrophy (VVA) that requires treatment, but only 25 % of these women seek treatment. Seventy-five percent of postmenopausal women suffer vaginal dryness; 15 % complain of vulvovaginal itching, discharge, and pain (The North American Menopause Society Menopause 2013).
It is important for physicians to have a clinical interest in maintaining the sexual function and erotic value of the vagina and vulva of their patients (even if these do not specifically and clearly ask for help), with a clinically accurate diagnosis and treatment (Nappi et al. 2016).
8.4.3 Undertreated
The underreporting and underdiagnosing of VVA itself lead to undertreatment of the condition. The REVIVE US survey among postmenopausal US women with VVA revealed that only 40 % was using any form of treatment, with those who discussed the condition with their doctor being twice as likely to have treatment than those who did not (Kingsberg et al. 2013).
In the VIVA survey, just under half (49 %) of all women with VVA complaints had tried lubricants and moisturizers, but these do not treat the underlying condition (Nappi and Kokot-Kierepa 2012), and the efficacy on vaginal symptoms is lower than that of topical estrogen therapy in the trials published thus far. Systemic HRT, on the other hand, relieves vaginal atrophy in about 75 % of women, but is usually not recommended in women with vaginal symptoms only (Sturdee and Panay 2010). The mainstay of treatment for VVA has been local vaginal estrogens. However, in the VIVA survey, 30 % of women said that they would not consider taking local estrogen therapy, even if they knew it to be effective (Nappi and Kokot-Kierepa 2012). In the REVIVE EU survey, less than half (45 %) of the participants were satisfied with their current treatment. For over-the-counter (OTC) products, the concerns were mainly about efficacy, and for local estrogens they were about safety (REVIVE EU 2015). Among those who expressed a preference for treatment administration, 55 % indicated they would prefer an oral product (Kingsberg et al. 2013). Finally, the labels of all local estrogens exclude women with a history of breast cancer and other hormone-dependent cancers, as systemic absorption has been demonstrated for these treatments (Labrie et al. 2009; Del Pup et al. 2012).
Key Point
Vulvovaginal atrophy in postmenopausal women can lead to symptoms, including vulvar and vestibular pain that significantly impact self-esteem, quality of life, and relationships.
There is a dire need to educate such women about the potential for effective treatment. Doctors and other healthcare providers should be willing to open up the conversation about vaginal health to assist in diagnosing and treating all those women who come to seek help.
8.5 Genital Arousal Disorders and Dyspareunia (GPPD) in VVA and GSM
Vaginal dryness is the first and leading symptom of VVA, and therefore of GSM, contributing to genital arousal disorders after the menopause. It may cause coital pain/dyspareunia. It is (still) neglected in the majority of women after the menopause for the abovementioned reasons.
Contributors include vaginal atrophy, vulvar dystrophy, and vestibular atrophy with hyperalgesia, the most neglected contributor to introital dyspareunia in postmenopausal women. In more rare cases, an (advanced) vulvar cancer may overlap with the atrophic changes.
Urogenital epithelium is particularly vulnerable to hormonal changes.
The characteristic vulvovaginal changes that occur during and after the menopause are due to the combination of physiological aging, hypoestrogenism, and hypoandrogenism. The latter is responsibile for the hormone-dependent involution of the cavernosal bodies (clitoral, bulbocavernous, and part of the equivalent of the male corpus spongiosum, around the urethra), of the androgen-dependent cells of the vulvar skin, of the connective tissue (fibroblasts and myocells), and of the nitrergic nerve fibers contributing to 1/3 of vaginal nerve fibers and the majority of vulvar nerve fibers. Notably, nitrergic fibers recognize testosterone as “permitting factor” potentiating the vascular-mediated genital arousal response in both genders.
8.6 Diagnosis: The Clinical Examination Is Key (also) After the Menopause
The vagina loses elasticity, shortens, narrows, becomes less distensible, and can, therefore, be easily traumatized and irritated. Vaginal secretions may decrease, and evidence of inflammation and small petechiae may be visible.
A watery, scalding discharge may be present and superficial fissuring is not an unusual finding, and lack of estrogen depletes vaginal intracellular glycogen, resulting in reduced lactobacilli bacteria, causing increased vaginal pH that should be recorded. Accurate physical examination is key (Box 8.3).
Box 8.3. Vulvovaginal Anatomic Changes Caused by Decreased Hormone Levels in Menopause (Figs. 8.1 and 8.2)
Fig. 8.1
Vestibule appears very thin with erosive appearance
Fig. 8.2
Atrophic changes of vulvar vestibule
Atrophy of vaginal epithelium
Reduction of pubic hair
Loss of fat and subcutaneous tissue from the mons pubis
Atrophy of the labia majora
Shortening and loss of elasticity of the vaginal barrel
8.7 The Vestibule: A Trigger of Vulvar Pain also After the Menopause
Very few studies on postmenopausal dyspareunia have been focused on location and quality of pain. It was reported that 95 % of menopausal women with dyspareunia also had localized provoked pain in the vestibule, despite the use of hormone supplements in 31 % of them (Kao et al. 2012a). The swab test remains a key for this specific diagnosis.
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