VAGINAL HEALTH IN WOMEN WHO HAVE HAD BREAST CANCER. Dana SAWAN MD, Barbara HERSANT MD, PhD.

Dr Dana Sawan

VAGINAL HEALTH IN WOMEN WHO HAVE HAD BREAST CANCER.

Dana SAWAN, MD (gynecologist) Barbara HERSANT, MD, PhD (plastic surgeon)

1 Department of Maxillo-facial, Plastic and Reconstructive Surgery. Hôpitaux Universitaires Henri-Mondor, 51, avenue Maréchal de Lattre de Tassigny, 94010 Créteil, France. dana.s.sawan@gmail.com

2 Henri Mondor Chirurgie thoracique, Hôpitaux Universitaires Henri-Mondor, 51, avenue Maréchal de Lattre de Tassigny, 94010 Créteil, France. Barbara.hersant@gmail.com

Summary

Most breast cancers are hormone-sensitive or estrogen-dependent. The therapeutic strategy is therefore to wean the body off its estrogen supply, which induces an early menopause in patients who are often still young and genitally active.

Menopause is accompanied by a series of general and local symptoms.

  • In the urogenital sphere, these are summarized in 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. The aim of this work is to do away with these means.
Key words: genitourinary syndrome of menopause, breast cancer, hormone therapy, alternatives, sex life.

INTRODUCTION

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

  • ¾ of breast cancers express estrogen receptors, including the 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 [6An increasing proportion of breast cancer survivors become postmenopausal at an earlier age after cancer treatment [...].7].

  • What's more, 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 (avv) or genitourinary syndrome of the menopause (sgum) [11].

 

However, this HS is risky in breast cancer survivors.

  • Indeed, it has been shown that current and former HS 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 HS [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 HS 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 mTMS, 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 (Cellular Matrix)
  • 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' quality of sexual life was also significantly improved, as shown by the decrease in the female sexual distress score one, three and six months after hyaluronic acid treatment [15...and platelet-rich autologous plasma https://vimeo.com/ manage/videos/758616976

Cellular Matrix INTIMACY

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

TREATMENT OF MENOPAUSAL GENITOURINARY SYNDROME (GUM):

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

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

  • Genital symptoms: - Dryness - Burning -
  • Sexual symptoms: - Lack of lubrication - Discomfort/pain - Impaired function.
  • Urinary symptoms: - Urgency - Dysuria - Recurrent urinary tract infections.
  • The cellular matrix is also being evaluated for lichen sclerosus, bartholinitis, Caesarean section scars, episiotomy scars and stretch mark treatments.
  • 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].

Vaginal laser therapy

Laser therapy has recently been proposed as a viable treatment for MGS.

  • 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].

Laser co2 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 had comparable improvements in GSM symptoms and sexual function after six months of follow-up. Approximately 70 to 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 laser: YAG has also been satisfactorily tested in MGS, 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 MUMS.
  • The main concern is the safety of this treatment, as the systemic passage of estrogens 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.
  • The aspects that put some patients off 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 at a dose of 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 estradioids over a prolonged period of time.l at a dose of 7.5 mg per day and can remain in place for 90 days [...25].

  • This local hormone therapy should be used only when non-hormonal methods do not work, and if possible for a limited period.
  • Long-term use can be made in patients on tamoxifen or raloxifene [22, 26, 27].
  • These block the possible estrogenic effect in case of significant systemic passage.
  • Hormone therapy should be avoided in any patient with unlabeled vaginal bleeding.
  • Similarly, bleeding that occurs during intravaginal hormone therapy should be investigated seriously (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 the target organs.

  • At present, only ospemifene is used in the management of MGS (60 mg/day), notably in the treatment of moderate to severe dyspareunia.
  • It improves the 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, combined with equine estrogens (20/0.45 mg daily), they significantly improved signs and symptoms of MGS 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 MGS (dyspareunia, vaginal maturation index, pH).
  • DHEA is believed to exert its vaginal effects through conversion in situ in 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 it [...].31].

" Non-medical means

Education

Women need to be educated about the changes that occur due to estrogen decline.

  • Many patients are unaware of these changes and therefore cannot seek appropriate medical help.
  • They need to know that the symptoms and signs of MGS 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 pain during intromission that is the result of vaginal dryness.

  • Lubricants are used at the time of intercourse, while humidifiers are used at a distance [ ].32]. There are water- 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 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, whether patients have a sexual partner or not [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 who specializes in pelvic pathology.

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

Lidocaine topical

Aqueous lidocaine 4 % applied in the vulvar vestibule a few minutes before intercourse significantly reduces the pain of penetration.

  • It can be used as an adjuvant to other measures (lubricants, humidifiers, rehabilitation) [35].

CONCLUSION

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

It poses a management problem because all modalities including estrogens must be either ruled out or carefully weighed on the risk/benefit balance.

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

References

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