Management of menopausal symptoms after breast cancer

Menopause is the time after someone’s final natural menstrual period, when the monthly cycle of ovarian hormones stops, the person no longer ovulates and oestrogen levels are low. In the UK, the average age of natural menopause is about 51 years. There are hormonal changes in the years leading up to the final period and for a short time after the final period – this whole time is known as the perimenopause.

Fluctuating oestrogen levels in the perimenopause and low oestrogen levels in the menopause can cause menopausal symptoms. These can start many months or years before the final menstrual period. After the final menstrual period, some menopausal symptoms reduce over months or years as the person’s body adapts to the low oestrogen levels, but others can persist or worsen over time after the final period.

Chemotherapy can cause ovarian insufficiency with resulting menopausal symptoms. Medical breast cancer treatments including tamoxifen, aromatase inhibitors (AI) like letrozole, anastrazole and exemestane, and GnRH analogues/antagonists can themselves cause or worsen menopausal symptoms. This is because they either block the activity of oestrogen at receptors or prevent production of oestrogen in the body making serum oestrogen levels very low.

Ovarian function is driven by hormones produced by the pituitary gland. In the perimenopause, the ovaries become more resistant to stimulation by these hormones. This means that the level of pituitary follicle stimulating hormone (FSH) rises as the pituitary tries to drive the ovaries, and serum estradiol falls as ovarian function reduces.

After the final menstrual period, serum FSH levels are consistently elevated, and serum estradiol is consistently low. In the perimenopause, however, an individual’s serum FSH can be very high when it is tested, and completely normal a few weeks later (or vice versa); serum estradiol levels similarly fluctuate widely. A normal hormone profile does not, therefore, exclude perimenopause as a cause of symptoms. And a hormone profile consistent with perimenopause (elevated FSH, low estradiol) supports the diagnosis of perimenopause but does not exclude future ovarian activity and ovulation.

Diagnosing menopause (future ovulation can reasonably be excluded)

Unless someone has had both ovaries removed, it is very difficult to know when ovulation has permanently stopped and a diagnosis of menopause can be made. There is not, unfortunately, a test that will definitively establish that the final menstrual period has passed and that the person will not ovulate again: elevated serum FSH does not exclude future ovulation. However:

• We can be fairly confident that someone has passed their final menstrual period (and guidance indicates that they no longer require contraception)¹ if they are naturally amenorrhoeic for a year after they are 50. This does not include people that have been amenorrhoeic because of hormonal contraception or use of another hormonal treatment, or people who become amenorrhoeic because of a medical treatment like chemotherapy or use of a GnRH analogue.
• If someone aged 50 or over has serum FSH > 30IU/L (without having had gonadotoxic medical treatment like chemotherapy) it is established practice that contraception can be stopped after one further year – the risk of pregnancy thereafter is very low¹. Guidelines indicate that contraception is not required after age 55¹.
• For people who are under 50 (especially if they are much younger), people who are using hormonal contraception or hormone/ anti-hormone treatments and people who have had gonadotoxic medical treatments like chemotherapy, future recovery of ovarian function cannot be excluded by hormone testing or by presence of menopausal symptoms.
• Contraception should always be discussed if future ovulation cannot be excluded- see Contraception section.

Diagnosing perimenopause as a cause of symptoms (future ovulation cannot be excluded)

There is not, unfortunately, a test that that will reliably inform whether ovarian function will recover.

• For people aged > 45 years, a diagnosis of perimenopause can be made based on typical menopausal symptoms. Hormone testing is not generally recommended². At this age, typical symptoms are very likely to indicate perimenopause. FSH testing is of very limited benefit as (1) normal hormone profile would not exclude perimenopause as a cause of symptoms, and (2) elevated FSH with low serum estradiol would not exclude future ovarian activity/ ovulation.
• For people aged < 45 years, a hormone profile (serum FSH and estradiol) can be helpful to support an uncertain diagnosis of perimenopause as a cause of symptoms but could be normal despite perimenopause². Even if FSH is elevated and estradiol low on the day of testing, consistent with ovarian insufficiency/perimenopause, ovarian function could resume subsequently and future ovulation cannot be excluded. This has implications for requirement for contraception as well as for choice of anti-oestrogen treatment.
• After gonadotoxic chemotherapy, ovarian function is often suppressed, with elevated serum FSH and low serum estradiol levels. For some people, this will be permanent: they are menopausal. For others, however (particularly younger people), there could be recovery of some ovarian activity even if the initial FSH levels are very high. Future ovulation cannot be excluded.
• Hormone profile can be affected by use of selective oestrogen receptor modulators like tamoxifen, aromatase inhibitors like letrozole, anastrazole and exemestane and GnRH analogues/antagonists. If it is considered important to check serum FSH and estradiol (bearing in mind the diagnostic limitations of those tests), tamoxifen should be stopped 12 weeks and aromatase inhibitors 4 weeks before sampling.

For some people menopausal symptoms are very mild, but for other people symptoms like flushes and sweats (vasomotor symptoms, VMS), mood problems, irritability and anxiety, difficulty with memory and concentration, poor sleep, musculoskeletal aches and pains, weight gain, loss of libido, vaginal dryness, dyspareunia and urinary symptoms can badly affect quality of life. Anti-oestrogen treatments for breast cancer often cause or worsen menopausal symptoms.

It is important to bear in mind that people can have symptoms similar to those experienced in menopause that relate to psychosocial and other medical causes including chemotherapy.

Some menopausal symptoms like flushes and sweats will generally improve by themselves over a few years (often around 7 years, but there is wide variation), but some people need help with managing them until they improve. Other menopausal symptoms may not improve over time, or may worsen, so it is useful to think about self-help strategies for these in addition to possible medical treatment options.

Oestrogen helps to maintain bone mineral density and muscle mass and has a cardioprotective effect. People who have perimenopause/menopause at a younger age have a greater risk of developing osteopenia/ osteoporosis. They lose muscle mass and lose the cardioprotective effect. Good dietary calcium and vitamin D intake and weight-bearing exercise are important for bone and muscle health, and people should be encouraged to optimise cardiovascular risk factors.

After breast cancer (regardless of hormone receptor status of the tumour) guidance currently recommends avoiding use of systemic hormone replacement therapy (HRT) for menopausal symptoms^3,4. This is because of concern that HRT could increase risk of breast cancer recurrence, or of occurrence of another primary breast cancer. Self-help strategies and non-hormonal medical treatment options should be recommended in the first instance^3,4,5.

Self-help strategies

There are lots of things that people can do themselves that are very useful for keeping menopausal symptoms under control and reducing their impact. Strategies for managing flushes and sweats include avoiding hot drinks, caffeine, alcohol and spicy foods which can trigger flushes and sweats; wearing layers of thin clothing that can be removed when needed, having thin layers of bedding that can be adjusted, rather than a single heavy layer; and using fans.

Mindfulness and cognitive behavioural therapy (CBT) techniques can help people to stay calm when they feel a flush or sweat starting, or when they feel angry or irritable or stressed by memory or concentration letting them down or being unable to sleep. CBT in particular has been shown to reduce flushes, sweats, low mood, anxiety and sleep disturbance⁶. The Women’s Health Concern fact sheet on Cognitive Behavioural Therapy for menopausal symptoms, and the self-help book “Managing hot flushes and night sweats: a cognitive behavioural self-help guide to the menopause” by Myra Hunter and Melanie Smith may be helpful, alongside online resources and apps like Sleepstation, Clementine and Sleepio (there are lots of others) for mindfulness and sleep. Podcasts from Menopause and Cancer organisation offer useful advice and support.

Exercise and maintaining a healthy weight can help hugely with symptoms and with self-esteem as well as being important for a healthy body. After menopause (and after some breast cancer treatments) muscle strength is lost and bone density reduces. Exercise and a good diet containing plenty of calcium and vitamin D can help to maintain muscle and bone strength to maintain mobility and protect bones from osteoporosis. Exercise doesn’t have to be strenuous – walking and climbing stairs are what suit some people best; others might opt for yoga or Pilates or swimming (or something completely different that makes them feel good). See the Women’s Health Concern factsheets on nutrition, exercise and weight gain in menopause.

Non-hormonal medical treatments

There are various non-hormonal medical treatments that can be used off-label after breast cancer for menopausal symptoms. These are drugs that are not intended for menopausal symptoms but can offer significant benefit.

• Selective serotonin reuptake inhibitors (SSRI’s) like †citalopram and †escitalopram and the serotonin and noradrenaline reuptake inhibitor (SNRI) †venlafaxine can be effective for mood changes that can occur in menopause but are also beneficial for flushes and sweats. Venlafaxine may also help with sleep^4,5,6,24. Before initiating any medicines, consider co-morbidities, the risk of interaction with other medicines and the impact of potential side effects. Suggested doses are:
• • †Venlafaxine 37.5mg taken orally once or twice a day
  • †Citalopram 10-20mg taken orally once a day
  • †Escitalopram 5-20mg taken orally once a day
  • For women taking tamoxifen, concurrent treatment with potent inhibitors of the enzyme CYP2D6 (paroxetine, fluoxetine) which catalyses conversion of tamoxifen to its active metabolite should be avoided^4,7.
• †Gabapentin (100-300mg orally three times a day) can be very useful for vasomotor symptoms, aches and pains and sleep^4,24.
• Clonidine is licensed for management of vasomotor symptoms, but benefit is very short-lived.
• †Oxybutynin 2.5mg po starting at a once daily dose and increasing to 4 times daily as required and tolerated can reduce wet sweats effectively but can have side effects like dry mouth and can affect cognition in the over-60s²⁵.

These treatment options can all be offered by the Breast Clinic or in Primary Care.

A new class of drugs, neurokinin3 (NK3) antagonists, are now licensed in the UK but have not yet been approved for use in the NHS. These are non-hormonal drugs that offer a modest improvement in frequency and severity of moderate to severe vasomotor symptoms^8,9. Evidence specific to use after breast cancer and during use of hormonal breast cancer treatments is lacking¹⁰.

See also non-hormonal treatment options specific to genitourinary symptoms below.

What about herbal or “natural” treatments?

Herbal treatments for menopause are not recommended because study evidence for their effect on breast cancer risk and their adverse health effects is not available. Many herbal menopause treatments, including red clover, phytoestrogens and black clover work by having a hormone-like effect, and can stimulate hormone receptors even if they are plant-based, or “natural”. Herbal medicines are not subject to the same trials and regulations as conventional medicine, so the content and strength of different preparations can vary hugely. Herbal medicines should be avoided after breast cancer^4,5.

Changes to adjuvant anti-oestrogen breast cancer treatments.

People whose menopausal symptoms are made worse by tamoxifen, or by an aromatase inhibitor (used with or without a GnRH analogue/antagonist) and for whom self-help and non-hormonal management strategies are not effective should consult with their breast cancer specialist, and dependent on the characteristics of their breast cancer be may able to consider strategies like:

• changing tamoxifen brand, splitting tamoxifen doses, or taking a 12-week tamoxifen holiday (while keeping a symptom diary to inform benefit)
• switching to a different aromatase inhibitor, switching from an aromatase inhibitor to tamoxifen or taking a 4-week aromatase inhibitor holiday (and keeping a symptom diary to inform benefit)⁴.

The vagina and the lower part of the urinary tract are very sensitive to low oestrogen levels. The vagina becomes drier and less robust: thinner, less elastic tissues make sex uncomfortable or painful. Some people experience urinary frequency, dysuria or frequent urine infections. Severe symptoms and serious adverse health events like urosepsis are not uncommon. Genitourinary atrophic symptoms often worsen over time after menopause and can be exacerbated by breast cancer treatments, particularly GnRH analogues/antagonists and aromatase inhibitors.

Non-hormonal treatment options for genitourinary syndrome of menopause.

A good lubricant like Yes^® or Sylk^® is recommended for intercourse, but in addition, a regular vaginal moisturiser like Yes^®, Sylk^®, or Hyalofemme^® can make the vagina much more comfortable. Soap and shower gel can dry and irritate the external genital skin, therefore washing with an soap substitute (such as QV^® or Hydromol^®) is helpful. This should be first line management for vaginal atrophic symptoms after breast cancer.

If an individual is still struggling with vaginal or urinary symptoms despite non-hormonal options they may be able to consider use of local vaginal hormone treatments or changes to their hormonal breast cancer treatment.⁴ This is dependent on the characteristics of their breast cancer and its treatment and the severity of the genitourinary symptoms.

Low or very low dose local vaginal oestrogen.

There are no studies which have assessed the risk of breast cancer recurrence with low dose vaginal oestrogen, however there is limited systemic absorption from low dose local vaginal oestrogen preparations (a small initial increase in serum oestrogens normalises with established use to post-menopausal levels)¹². Theoretically any effect of low dose local vaginal oestrogen (particularly very low dose estriol preparations) on breast cancer risk would be expected to be very small^11-13.

During use of tamoxifen, activity at breast receptors of any small amount of local vaginal oestrogen absorbed systemically would be expected to be blocked. Limited study evidence suggests no increase in risk of breast cancer recurrence when local vaginal oestrogen is used concurrently with tamoxifen after early-stage non-metastatic breast cancer^14,15. There is generally less concern during tamoxifen use about potential effect of use of low dose local vaginal oestrogen on breast cancer risk than there is during use of aromatase inhibitors¹³. It is noted that in the post-menopause, tamoxifen has an agonist effect at vaginal oestrogen receptors and can itself offer benefit for atrophic symptoms in this population.

During use of aromatase inhibitors (when systemic oestrogen levels are exceptionally low) urogenital symptoms are frequent and can be severe. There is concern that in this situation absorption of even small amounts of oestrogen from low dose local vaginal products could affect subsequent breast cancer risk.¹⁵  Available evidence indicates significant benefit of very low dose vaginal estriol preparations for symptoms of vulvovaginal atrophy during use of aromatase inhibitors with minimal systemic absorption of estriol once treatment is established^16,17,18 but is as yet too limited to inform effect on breast cancer risk.

Effect of use of low dose local vaginal oestrogen on breast cancer risk following oestrogen-receptor negative breast cancer is not known. Some guidance suggests that there could be less concern about use of local vaginal oestrogen than after oestrogen receptor positive breast cancer¹³.

The British menopause society consensus statement recommends:

1. Topical estrogen should not be used if a woman is using an aromatase inhibitor due to concern systemic absorption (albeit very low) may negate the latter’s efficacy.
2. If a woman is using an aromatase inhibitor, switching to tamoxifen may ameliorate symptoms. This beneficial effect can take up to three months to become evident.
3. If switching to tamoxifen fails to improve symptoms, additional prescription of low-dose topical estrogen can be considered.
4. No changes to breast cancer medication should be initiated in primary care. Discussion with the breast specialist team is obligatory, as changes to therapy could potentially affect disease-free survival, particularly in higher-risk women.

Preparations include: low dose vaginal estradiol 10mcg tablets, vaginal estradiol ring, estriol cream (500µg estriol per application), and the newer very low dose preparations: estriol pessaries (30µg estriol per application) and vaginal estriol gel (50µg estriol per application) all of which are inserted directly into the vagina.

Other potential management options for menopausal genitourinary symptoms include the following:

• The selective oestrogen receptor modulator (SERM) ospemifene has benefit for urogenital atrophic symptoms and bone density, with minimal apparent adverse effect on endometrium. Ospemifene appears to have an antagonist effect at breast oestrogen receptors and is licensed in the UK for use for management of vaginal symptoms but due to lack of data in breast cancer, use is reserved following completion of all breast cancer treatment. There is a lack of evidence regarding long-term risk of occurrence or recurrence of breast cancer if ospemifene is used concurrently with anti-estrogen breast cancer treatments⁴. Furthermore, ospemifene can cause vasomotor symptoms and is associated with modestly increased VTE risk¹⁴.
• Vaginal dehydroepiandrosterone (DHEA, prasterone) has apparent benefit for urogenital symptoms when compared to placebo¹⁹. Studies report small but short-lived increases in serum estradiol levels during initial use of vaginal DHEA in the postmenopause (although not during concomitant use of an aromatase inhibitor) ²⁰. Evidence to inform outcomes associated with use by individuals who have or have had breast cancer is very limited and at present guidance does not support routine use^{5,12,14,20,21}.
• Vaginal laser treatment is of short term benefit for urogenital atrophic symptoms but evidence is lacking to inform longer term outcomes and UK guidance does not currently support use^4,19.

As a last resort, some people with severe ongoing menopausal symptoms refractory to non-hormonal treatment options and changes in breast cancer treatment could be considered for systemic HRT. 

Discussion with their breast specialist must cover the associate risk of using systemic HRT after breast cancer and prescribers should note this is an off-label use⁵.

Any decision to use systemic HRT will be dependent on multiple factors including the type of breast cancer, outcome of breast cancer treatment, time since treatment (or type of ongoing treatment), the patient’s age and other medical diagnoses, the nature and severity of menopausal symptoms the response to non-hormonal management options and patient preference. It is recommended that any decision to use systemic HRT should involve the individual’s specialist breast clinician with input from specialist menopause clinicians⁴.

What is systemic HRT?

HRT replaces oestrogen to help with menopausal symptoms. Unfortunately, if oestrogen is given alone, it can overstimulate endometrium, with potential risk of endometrial hyperplasia and endometrial cancer. Therefore, unless someone has had a total hysterectomy AND has never had endometriosis, they will need a progestogen as part of HRT to protect the endometrium and/or endometriotic deposits from oestrogen.

Use of HRT after breast cancer

There is no consistent, robust evidence to inform the effect of use of oestrogen alone or combined oestrogen and progestogen HRT on breast cancer risk for someone that has already had any breast cancer (regardless of the receptor status, grade and stage of the breast cancer). The use of HRT is avoided if at all possible after any breast cancer because of concern about increased risk of recurrence or a further primary breast cancer^3,5. Systemic HRT should always be avoided during use of an aromatase inhibitor^3,4,22,23.

Looking at the evidence that is available³, studies of people who have not had breast cancer indicate that use of any combined HRT is associated with increased risk of breast cancer. This includes HRT that uses a levonorgestrel-releasing IUD (LNG-IUD) like Mirena^®, Levosert^®or Benilexa^® as the progestogen component. It is possible that HRT containing micronised progesterone or dydrogesterone as the progestogen component could confer a slightly smaller increase in breast cancer risk than HRT containing some other synthetic progestogens³. Extrapolating from this, if a decision was made to prescribe combined HRT after a breast cancer, a clinician might choose to use micronised progesterone or dydrogesterone as the progestogen. There is not, however, clear direct evidence to inform whether the type of progestogen in HRT affects risk of breast cancer recurrence or occurrence of another primary breast cancer.

Systemic oestrogen used alone without a progestogen appears to have a lesser effect than combined HRT on breast cancer risk in the general population, but like combined HRT it is generally avoided after breast cancer³.

It is important for people who have menopausal symptoms but for whom HRT is not recommended to know that while many menopausal symptoms improve with HRT, it does not help with all the symptoms that people experience in perimenopause/menopause. Additionally, symptoms that do respond to HRT often recur whenever HRT is stopped again (although they could have a lesser impact at a different stage in someone’s life). Importantly, self-help strategies are as important as HRT for many people in management of menopausal symptoms.

1. FSRH Clinical Guideline: Contraception for Women Aged over 40 Years (August 2017, amended July 2023) FSRH Clinical Guideline: Contraception for Women Aged over 40 Years (August 2017, amended July 2023) - Faculty of Sexual and Reproductive Healthcare (accessed 30/10/2023).
2. NICE Guideline NG23. Menopause: Diagnosis and Management 92015, (updated 2019) Overview | Menopause: diagnosis and management | Guidance | NICE (accessed 30/10/2023).
3. Marsden J, Pedder H. The risks and benefits of hormone replacement therapy before and after a breast cancer diagnosis. Post Reproductive Health. 2020;26(3):126-135. doi:10.1177/2053369120956636.
4. Marsden J. The British menopause society consensus statement on the management of oestrogen deficiency symptoms, arthralgia and menopause diagnosis in women with treated for early breast cancer. Post Reproductive Health. 2022;28(4):199-210. doi:10.1177/20533691221122358.
5. Early and locally advanced breast cancer: diagnosis and management. NICE guideline [NG101]Published: 18 July 2018 Last updated: 14 June 2023 Recommendations | Early and locally advanced breast cancer: diagnosis and management | Guidance | NICE (accessed 30/10/2023).
6. Diem SJ, LaCroix AZ, Reed SD, et al. Effects of pharmacologic and nonpharmacologic interventions on menopause-related quality of life: a pooled analysis of individual participant data from four MsFLASH trials. Menopause. 2020;27(10):1126-1136. doi:10.1097/GME.0000000000001597.
7. Review of available evidence at Stockleys Drug interactions MedicinesComplete — CONTENT > Stockley's Drug Interactions > Interaction: Tamoxifen + SSRIs and other CYP2D6 inhibitors (accessed 30/10/2023).
8. Johnson KA, Martin N, Nappi RE, et al. Efficacy and Safety of Fezolinetant in Moderate to Severe Vasomotor Symptoms Associated With Menopause: A Phase 3 RCT, The Journal of Clinical Endocrinology & Metabolism, Volume 108, Issue 8, August 2023, Pages 1981–1997, https://doi.org/10.1210/clinem/dgad058.
9. Lederman S, Ottery FD, Cano A, et al. Fezolinetant for treatment of moderate-to-severe vasomotor symptoms associated with menopause (SKYLIGHT 1): a phase 3 randomised controlled study. Lancet. 2023;401(10382):1091-1102. doi:10.1016/S0140-6736(23)00085-5.
10. Gompel A, Stuenkel CA. Neurokinin 3 receptor antagonists for menopausal vasomotor symptoms, an appraisal. Cell Rep Med. 2023 Jun 20;4(6):101076. doi: 10.1016/j.xcrm.2023.101076. PMID: 37343519; PMCID: PMC10313926.
11. Sulaica, E., Han, T., Wang, W., Bhat, R., Trivedi, M. V., & Niravath, P. (2016). Vaginal oestrogen products in hormone receptor-positive breast cancer patients on aromatase inhibitor therapy. Breast cancer research and treatment, 157, 203-210.
12. Hussain I, Talaulikar VS. A systematic review of randomised clinical trials – The safety of vaginal hormones and selective oestrogen receptor modulators for the treatment of genitourinary menopausal symptoms in breast cancer survivors. Post Reproductive Health. 2023;0(0). doi:10.1177/20533691231208473.
13. Faubion, S. S., Larkin, L. C., Stuenkel, C. A., Bachmann, G. A., Chism, L. A., Kagan, R., .. & Kingsberg, S. A. (2018). Management of genitourinary syndrome of menopause in women with or at high risk for breast cancer: consensus recommendations from The North American Menopause Society and The International Society for the Study of Women's Sexual Health. Menopause, 25(6), 596-608.
14. Le Ray, I., Dell’Aniello, S., Bonnetain, F. et al.Local oestrogen therapy and risk of breast cancer recurrence among hormone-treated patients: a nested case–control study. Breast Cancer Res Treat135, 603–609 (2012). https://doi.org/10.1007/s10549-012-2198-y.
15. Cold S, Cold F, Jensen M-B et al. Systemic or Vaginal Hormone Therapy After Early Breast Cancer: A Danish Observational Cohort Study, JNCI: Journal of the National Cancer Institute, Volume 114, Issue 10, October 2022, Pages 1347–1354, https://doi.org/10.1093/jnci/djac112.
16. Hirschberg, Angelica Lindén MD, PhD; Sánchez-Rovira, Pedro MD, PhD; Presa-Lorite, Jesús MD; Campos-Delgado, Miriam MD; Gil-Gil, Miguel MD; Lidbrink, Elisabet MD, PhD; Suárez-Almarza, Javier Pharm, BSND; Nieto-Magro, Concepción MD, PhD. Efficacy and safety of ultra-low dose 0.005% estriol vaginal gel for the treatment of vulvovaginal atrophy in postmenopausal women with early breast cancer treated with nonsteroidal aromatase inhibitors: a phase II, randomized, double-blind, placebo-controlled trial. Menopause 27(5):p 526-534, May 2020. | DOI: 10.1097/GME.0000000000001497.
17. Pavlović RT, Janković SM, Milovanović JR, et al. The Safety of Local Hormonal Treatment for Vulvovaginal Atrophy in Women With Oestrogen Receptor-positive Breast Cancer Who Are on Adjuvant Aromatase Inhibitor Therapy: Meta-analysis. Clin Breast Cancer. 2019;19(6):e731-e740. doi:10.1016/j.clbc.2019.07.007.
18. Buchholz S, Mögele M, Lintermans A, et al. Vaginal estriol-lactobacilli combination and quality of life in endocrine-treated breast cancer. Climacteric. 2015;18(2):252-259. doi:10.3109/13697137.2014.991301.
19. Merlino L, D’Ovidio G, Matys V, Piccioni MG, Porpora MG, Senatori R, Viscardi MF, Vitale A, Della Rocca C, on behalf of Policlinico Umberto I Collaborators. Therapeutic Choices for Genitourinary Syndrome of Menopause (GSM) in Breast Cancer Survivors: A Systematic Review and Update. Pharmaceuticals. 2023; 16(4):550. https://doi.org/10.3390/ph16040550.
20. Barton DL, Sloan JA, Shuster LT, Gill P, Griffin P, Flynn K, Terstriep SA, Rana FN, Dockter T, Atherton PJ, Tsai M, Sturtz K, Lafky JM, Riepl M, Thielen J, Loprinzi CL. Evaluating the efficacy of vaginal dehydroepiandosterone for vaginal symptoms in postmenopausal cancer survivors: NCCTG N10C1 (Alliance). Support Care Cancer. 2018 Feb;26(2):643-650. doi: 10.1007/s00520-017-3878-2. Epub 2017 Sep 18. PMID: 28921241; PMCID: PMC5754227.
21. Kearley-Shiers K, Holloway D, Janice Rymer, Bruce D. Intravaginal dehydroepiandrosterone for genitourinary symptoms of the menopause: Is the evidence sufficient? Post Reproductive Health. 2022;28(4):237-243. doi:10.1177/20533691221135906.
22. Holmberg L., Anderson H. HABITS steering and data monitoring committees: HABITS (hormonal replacement therapy after breast cancer—Is it safe?), a randomised comparison: Trial stopped. Lancet. 2004;363:453–455. doi: 10.1016/S0140-6736(04)15493-7.
23. Von Schoultz E., Rutqvist L.E. Stockholm Breast Cancer Study Group: Menopausal hormone therapy after breast cancer: The Stockholm randomized trial. J. Natl. Cancer. Inst. 2005;97:533–535. doi: 10.1093/jnci/dji071.
24. Rada G, Capurro D, Pantoja T, Corbalán J, Moreno G, Letelier LM, Vera C. Non-hormonal interventions for hot flushes in women with a history of breast cancer. Cochrane Database Syst Rev. 2010 Sep 8;(9):CD004923. doi: 10.1002/14651858.CD004923.pub2. PMID: 20824841.
25. NICE Evidence summary ES10. Hyperphidrosis: oxybutynin (published 2017) Hyperhidrosis: oxybutynin (nice.org.uk).
26. Senshio 60 mg film-coated tablets - Summary of Product Characteristics (SmPC) - (emc) (medicines.org.uk) accessed 8.2.24.