VAGINAL HEALTH IN WOMEN WHO HAVE HAD BREAST CANCER

Dana SAWAN MD | gynecologist | Barbara HERSANT MD, PhD | Plastic Surgeon

Dana SAWAN : Department of Maxillofacial, Plastic and Reconstructive Surgery. Hôpitaux Universitaires Henri- Mondor, 51, avenue Maréchal de Lattre de Tassigny, 94010 Créteil, France.

Barbara HERSANT : Henri Mondor Chirurgie thoracique, Hôpitaux Universitaires Henri-Mondor, 51, avenue Maréchal de Lattre de Tassigny, 94010 Créteil, France.

Summary

Most breast cancers are hormone-sensitive or estrogen-dependent.

The therapeutic strategy is therefore to wean the body off estrogen, which induces an early menopause in patients who are often still young and genitally active.

The menopause is accompanied by a series of general and local symptoms.

In the urogenital sphere, these can be summed up as a so-called genitourinary menopause syndrome (vaginal dryness, atrophy, dyspareunia, dysuria, etc.).

Treatment of this syndrome relies heavily on estrogen. Yet estrogen carries a risk of recurrence in patients with a history of breast cancer.

It is therefore imperative to find alternatives to hormonal treatment. This work aims to eliminate the reliance on these methods.

Keywords: genitourinary syndrome of menopause, breast cancer, hormone therapy, alternatives, sex life.

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INTRODUCTION

Breast cancer is the most common cancer and the leading cause of cancer-related death in women.

3/4 of breast cancers express estrogen receptors, including Estrogen Receptor alpha (ERa) [1, 2, 3, 4].

Tumors that do not express estrogen receptors often express epidermal growth factor receptor (EGFR).

The latter has been correlated with larger tumors and metastatic forms [5].

The hormone-sensitivity and hormone-dependence of breast cancer makes hormone therapy one of the principal means of treating these cancers.

It consists in weaning them off the estrogen supply that sustains their growth, either by suppressing endogenous production (chemotherapy or ovarian irradiation), or by systemically administering an anti- estrogen substance.

Advances in breast cancer detection technology now make it possible to detect tumors at an earlier stage than before and, given that adjuvant chemotherapy is associated with ovarian failure [6], an increasing proportion of breast cancer survivors become postmenopausal at an earlier age after cancer treatment [7].

In addition, estrogen levels gradually decline as menopause approaches, which can lead to the appearance of particular and disabling genital and urinary symptoms in the women concerned [8].

Hormone replacement therapy (HRT) is known to be effective and recommended for controlling menopausal symptoms such as hot flushes, sleep disorders, sexual dysfunction or vaginal atrophy, and even preventing osteoporosis and cardiovascular disease [9, 10].

In general, systemic estrogen therapy is recommended for women with general symptoms, while local estrogen therapy is recommended for those suffering from VulvoVaginal Atrophy (VVA) or Genitourinary Syndrome of Menopause (GSM) [11].

In general, systemic estrogen therapy is recommended for women with general symptoms, while local estrogen therapy is recommended for those suffering from VulvoVaginal Atrophy (VVA) or Genitourinary Syndrome of Menopause (GSM) [11].

However, HRT is risky for breast cancer survivors.

Indeed, it has been shown that current and former HRT users have a higher risk of developing breast cancer because estrogen plays a central role in the development of breast cancer [12].

Thus, women who have received primary treatment for early-stage breast cancer may have a recurrence of the disease after HRT [13].

Clinicians must therefore consider the goals of systemic endocrine therapy and the safety of this treatment modality in healthy women and those with a history of breast cancer [11].

Given the safety concerns surrounding the use of HRT in women with a history of breast cancer, this paper examines alternatives to estrogen replacement therapy that may help address specific survivorship issues such as GSM, in this group of women.

ALTERNATIVES TO HORMONE REPLACEMENT THERAPY

Several alternatives to the use of hormone replacement therapy have been proposed to women who have already been diagnosed with breast cancer.

Medical resources

Autologous platelet-rich plasma and hyaluronic acid (Regen Lab®)

A multicenter, randomized, controlled, open-label study of 144 women found that hyaluronic acid vaginal gel was effective in improving vaginal dryness in postmenopausal women [14]. 

A recent phase 2 clinical trial suggested that intraperitoneal administration of a combination of autologous platelet-rich plasma and hyaluronic acid appeared to improve MUMS in women previously diagnosed with breast cancer [15].

The researchers reported a significant increase in the volume of vaginal secretions after the start of treatment.

The participants’ sexual quality of life was also significantly improved, as shown by the decrease in the female sexual distress score one, three and six months after treatment with hyaluronic acid [15] and autologous platelet-rich plasma. https://vimeo.com/manage/videos/758616976

 

RegenPRP™-HA conbination | Intimacy

The patient’s own platelet-rich plasma combined with hyaluronic acid to regenerate skin and mucous membranes.

TREATMENT OF GENITOURINARY SYNDROME OF MENOPAUSE (GSM):

  • New vascularization stimulated by the release of vascular endothelial growth factor (VEGF).
  • Increased elasticity thanks to new collagen and elastin
  • Overall reduction in pain and

GSM: Set of symptoms and signs associated with a decrease in estrogen.

  • Genital symptoms: – Dryness – Burning –
  • Sexual symptoms: – Lack of lubrication – Discomfort/pain – Impaired
  • Urinary symptoms: – Urgency – Dysuria – Recurrent urinary tract

The Cellular Matrix device is also being evaluated for lichen sclerosus, bartholinitis, Caesarean section scars, episiotomy scars and stretch mark treatments.

Vaginal laser therapy

Laser therapy has recently been proposed as a viable treatment for GSM. The use of vaginal carbon dioxide for menopause-related symptoms is somewhat new, and very few studies have explored its efficacy just 12 weeks after therapy [16, 17, 18].

A single-arm pilot study demonstrated that vaginal carbon dioxide laser improved VVA symptoms and sexual function[16].

In addition, a systematic review including six non-randomized studies suggested that vaginal carbon dioxide laser could improve vaginal health in women diagnosed with breast cancer [19].

The co2 laser used to reshape the vaginal epithelium activates heat shock proteins which in turn activate growth factors that increase vascularization, collagen, extra-cellular matrix production and vaginal mucosal thickness [20].

Recently, the VeLVET trial was conducted to compare the safety and efficacy of laser therapy with vaginal estrogen after six months’ follow-up [21].

The investigators found that women in the laser-treated group and the vaginal estrogen group showed comparable improvements in GSM symptoms and sexual function after six months’ follow-up.

Some 70-80% of women in both groups reported being satisfied or very satisfied with their treatment option.

No serious adverse events were reported by participants.

The erbium:YAG laser has also been satisfactorily tested in GSM, showing greater long-term efficacy than estriol [22].

 

Intravaginal use of estrogen gels or creams

The use of estrogen gels and creams brings significant relief to patients suffering from GSM.

The main concern is the safety of this treatment, as the systemic passage of estrogen is through the vaginal mucosa. Several studies suggest the safety of this treatment [23, 24].

Indeed, systemic estrogen levels remain very low, and the risk of cancer recurrence is not significantly elevated for estriol doses of 0.25 mg and estradiol between 12.5 and 25 mg.

Aspects that put off some patients are the «messy» nature of administration, the unhygienic reusable applicator and the approximate dosage, as there is often no dosing device, which is problematic in our population [25].

Administration is usually daily for the first two weeks, then twice weekly for the maintenance period. Intravaginal estradiol ova dosed at 4 mg are also safely used in breast cancer survivors [25].

They offer the advantage of precise dosage and easier application.

Based on the same principle, there are vaginal rings that release estradiol at a sustained rate of 7.5 mg

per day and can remain in place for up to 90 days [25].

This local hormone therapy should be used only when non-hormonal methods fail, and if possible for a limited period.

Long-term use is possible in patients on tamoxifen or raloxifene [22, 26, 27]. These block any estrogenic effect in the event of significant systemic passage.

Hormone therapy should be avoided in any patient with unlabelled vaginal bleeding.

Similarly, if bleeding occurs during intravaginal hormone therapy, it should be the subject of a serious investigation (imaging, endometrial biopsy).

Specific estrogen receptor modulators (SERMs)

These molecules are non-steroidal agents that exert a plethora of estrogen agonist or antagonist effects on target organs.

At present, only ospemifene is used in the management of GSM (60 mg/day), notably in the treatment of moderate to severe dyspareunia.

It improves maturation of the vaginal mucosa and acidifies the pH [25].

Tamoxifen has various effects on the vagina and can cause dyspareunia, increased white discharge or vaginal dryness [28].

Raloxifene and bazedoxifene have no direct effect on the vagina. However, in combination with equine estrogens (20/0.45 mg daily), they significantly improved signs and symptoms of GSM without causing endometrial hyperplasia [29].

Vaginal dehydroepiandrosterone (DHEA)

DHEA is a pro-hormone in the biosynthesis of testosterone and estradiol.

Trials have shown its effectiveness on the symptoms of GSM (dyspareunia, vaginal ripening index, pH). DHEA is thought to exert its vaginal effects through in situ conversion to testosterone and estradiol.

Serum levels are not elevated, as these products are locally inactivated [30]. It is therefore a safer alternative to local estrogens for breast cancer survivors.

Moreover, as aromatase does not exist in the endometrium, DHEA has no proliferative effect on the latter [31].

Non-medical means

Education

Women need to be educated about the changes that occur as estrogen declines.

In fact, many patients are unaware of these changes and therefore unable to seek appropriate medical help.

They need to know that the symptoms and signs of GSM will not regress spontaneously, and to be aware of the various treatment options available to them [25].

Lubricants and vaginal humidifiers

They offer an immediate solution to the problem of intromission pain resulting from vaginal dryness.

Lubricants are used at the moment of intercourse, while humidifiers are used at a distance [32]. There are water-based and silicone-based lubricants. The former do not stain and are better tolerated than the latter.

However, the effectiveness of lubricants depends on their osmolarity.

Osmolarity above 1,200 mOsm/kg is associated with irritation, contact dermatitis and cytotoxicity [32].

Humidifiers increase the hydration of the vaginal mucosa by adhering to it, imitating the vaginal secretions. They also contain additives that lower pH and affect osmolarity [32].

Use of vibrators and vaginal dilators

They help maintain sexual function by stretching vaginal and vulvar tissues. In fact, they stimulate these tissues and increase blood flow to them, whether or not patients have a sexual partner [25].

Women with vaginismus can use these conscious relaxation devices to facilitate the resumption of penetrative sexual activity [33].

Pelvic floor rehabilitation

Physiotherapy should ideally be guided by a professional specializing in pelvic pathologies.

It is indicated for women with pelvic muscle hypertonia caused by painful sexual activity secondary to GSM [34].

Lidocaine topical

4% aqueous lidocaine applied to the vulvar vestibule a few minutes before intercourse significantly

reduces the pain of penetration.

It can be used as an adjunct to other measures (lubricants, humidifiers, rehabilitation) [35

CONCLUSION

Genitourinary menopause syndrome is a consequence of breast cancer treatment, which deprives the body of its estrogen supply.

It poses a management problem, as all modalities including estrogen must either be ruled out or carefully weighed against the risk/benefit balance.

However, there are many other solutions that enable most patients to find the formula that’s right for them.

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