Menopause

the final menstrual period, determined after 12 months with no vaginal bleeding

CFReSHC CF-SRH Resource Guide by Patients for Providers and Patients

 

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Introduction

Menopause is the time that signifies the end of a woman’s menstrual cycles. It is marked when a woman has not had a period for 12 consecutive months and no other physiological cause can be identified. It denotes the end of a female’s childbearing years [1].

Menopause in CF is not a well-researched topic, because until recently, very few patients lived long enough to reach menopause. With better treatment options, patients are surviving longer, and more women with CF are entering this life phase. In the average life span, women will spend one-third of their life in menopause. Menopausal physical changes on average last four years to 10 years [2]. Studies promote hormone replacement therapy during this life phase to improve quality of life [2,3]. Therefore, an exploration of menopausal symptoms and treatments warrants exploration as women with CF look to differentiate CF symptoms from peri/postmenopausal physical changes and seek treatment options.  

 

Priority Questions on Menopause for Providers and Patients to ask during a Clinic Visit:

  • What is your cycle like currently– how many days between the first day of each period from one month to the next? How many days of bleeding? Are either of these a change for you?
  • Are you tracking if CF symptoms vary during different phases of your menstrual cycle? 
  • Have you experienced symptoms of perimenopause or menopause, such as hot flashes, sleep disturbances or depression? Have you noticed changes in your sex life, menstruation, vaginal lubrication, sleep patterns, and/or mood?
  • Have you discussed these changes with your OB/GYN or endocrinologist? 
  • Are you taking any over the counter supplements to help you through perimenopause/menopause?

Patient to CF Provider:

  • My gynecologist suggests I may have started perimenopause. How will this affect my CF care? 
  • What should I expect after menopause and what are your recommendations for hormone therapy, herbal menopause treatments, and my CF care at this life stage? 
  • What hormone therapies could interact with my current medications?
  • Do CFTR Modulators have any effect on perimenopause and menopause?
  • Do women with CF enter menopause early?                                                                                                                                                       

Patient to GYN provider: 

  • (For GYN) How does my CF care affect my hormones? Would you be willing to speak with my CF team about my issues?

Signs of Menopause:  

During perimenopause and menopause a variation in hormone levels can produce physiological and psychological changes. Women might experience some or all of the following:

Variations in frequency, duration and flow of periods

Incontinence/

Urinary tract infections

 Weight gain/slowing metabolism Hair growth on chin, upper lip and cheeks (face)
Mood changes/depression/anxiety Hot flashes/night sweats Vaginal dryness Painful intercourse (dyspareunia) and/or low libido
Interrupted sleep Muscle tone loss Hair loss/thinning Osteopenia/osteoporosis

                                                                                                  

Menopause is considered the day of a woman’s last period, defined after 365 days without menstruation. The time prior is considered perimenopause and the days following are termed post menopausal. During menopause, the sex hormones estrogen, progesterone and testosterone are reduced, which can lead to “atrophy of the vaginal mucosa, causing vaginal dryness, dyspareunia (painful intercourse), itching, vaginal stenosis and urinary incontinence” [3]. 

The menopause transition (MT) causes a variety of symptoms, such as lethargy, hot flashes, vaginal discharge, insomnia, osteoporosis, insulin resistance, and an increased risk of developing chronic conditions, such as diabetes and cardiovascular disease [4]. Anna Cyganek et. al (2018) find that 70-80% of women experience hot flashes, which range from mild to severe enough to negatively impact quality of life [5]. Citing Tsang’s work, the Cystic Fibrosis Foundation’s Adult Guide to CF reports that women with CF experience menopause an average of 2–3 years earlier than the general population. Tsang has noted the most significant reported perimenopausal changes for women with CF were sleep disturbance and depression [6].   

For its part, menopause research in the general population suggests that having a history of depression makes it more likely a woman will experience a depressive episode as she approaches menopause. Bromberger and Epperson (2018) recommend treating women for depressive symptoms experienced during this transitional phase and indicate that the risk of depression declines 2-4 years after the final menstrual period [7]. 

Implications of Menopause for Women with CF

Impact on Lung Function

A large, longitudinal study by Triebner examining the relationship between lung function and menopause across several European populations shows both FVC and FEV1 decline in women transitioning to menopause and for post-menopausal women, over and above declines expected with age. Further, the decline is more pronounced for FVC, suggesting that the link is related to airway restriction rather than obstruction. Real et al concur, and remark that lower lung function and increased respiratory symptoms are particularly found amongst “lean women” (BMI < 23) [8]. Several mechanisms may explain this link, including systemic inflammation, osteoporosis (which can reduce the ability to expand the thoracic cage) and insulin resistance [8]. This observed decline likely has ramifications for women with CF as well. 

Impact on Bone Health

Bone health, which is already an important factor in CF care, is of particular concern during the menopausal transition. Women experience a change in bone strength which can lead to osteoporosis and future fractures.9 Rapid bone loss occurs in the three years leading up to menopause and continues for three years after due to changes in sex steroid hormones [9].

Impact for Post-Transplant Women 

Post-transplant patients on immunosuppressive drugs might see more accelerated bone density loss. Additionally, women who have undergone a transplant might experience premature menopause. These women, seem to do well with hormonal therapy during menopause, but close monitoring is recommended [5].

Impact of Hormone Replacement Therapy (HRT)

HRT, also called hormone therapy or post-menopause hormone therapy, can help with night sweats, mood swings, hot flashes and reduced libido associated with menopause [2]. Options include estrogen-only therapy or estrogen–progestogen therapy (EPT) and patients should be well informed to weigh the benefits and potential risks [10]. HRT can be administered orally or topically with an intravaginal cream or patch. One concern about HRT is its effect on the liver. Some CF and transplant medications can be taxing on the liver and oral estrogen used to treat hot flashes also have a pronounced effect on the liver. Estrogen topical preparations avoid “the first-pass effect” of being primarily metabolized through the liver”[5]. 

Recent observational study has shown that there is an increased risk of breast cancer (or pre-invasive ductal carcinoma in situ) for women using combined HRT after >5 years of treatment. This risk increases with prolonged treatment…(and)… there was no increased risk of breast cancer seen for users of oestrogen-only therapy” [11,12]. Results from the Women’s Health Initiative (WHI) studies, which assessed the risks and benefits of HRT in postmenopausal (non-CF) women, indicate that [13,14]: 

  1. women who took estrogen alone or estrogen plus progestin had a lower risk of hip and vertebral fractures than women who took placebo; 
  2. women who took estrogen plus progestin had more vaginal bleeding that required assessment by endometrial biopsy than women who took placebo;
  3. women who took estrogen alone or estrogen plus progestin had an increased risk of urinary incontinence; 
  4. women age 65 and older who took estrogen alone or estrogen plus progestin had an increased risk of developing dementia, women who took either combined hormone therapy or estrogen alone had an increased risk of stroke, blood clots, and heart attack [11,12]; 
  5. women who took estrogen alone had a lower risk of breast cancer than women who took placebo [15] 
  6. women who took estrogen plus progestin were more likely to be diagnosed with breast cancer than women who took placebo and the risk of breast cancer was greater the longer women took the combined hormone therapy, but it decreased markedly when hormone use stopped [16];   
  7. and in the initial study report, women taking combined hormone therapy had a lower risk of colorectal cancer than women who took placebo [17].    

It is important to note that risks for the aforementioned diagnoses reduced when women stopped HRT [17].  

 

Treatment Options

While there are treatment options for MT, there is no cure except time.

  • HRT might supplement estrogen and progesterone levels to ease the symptoms that occur in (peri)menopause, like hot flashes, night sweats, or sleep disruption [13].  
  • SSRIs (selective serotonin reuptake inhibitors) and SNRIs (serotonin and norepinephrine reuptake inhibitors) might help with depression and hot flashes. Dr. Cynthia Stuenke, a founding member of the North American Menopause Society and a professor and endocrinologist at the University of California, San Diego, School of Medicine, says, “While they’re not perfect, they can take the edge off and help enough so that women can get a better night’s sleep” [18].
  • In 2015, a North American Menopause Society panel found that cognitive behavioral therapy and hypnosis were significantly effective in treating hot flashes. The same panel also found that popular herbal remedies (like black cohosh, dong quai and evening primrose) are “unlikely to help,” despite anecdotal reports that women find them helpful [18].  
  • Guided meditation and mindfulness to help with relaxation and mood swings.
  • Regular exercise can help with weight gain, metabolism changes, mood issues and joint pain.
  • To combat sleep disturbances, establish sleep habits and practices.

Are there Benefits to Menopause?

While there can be late life pregnancies in the perimenopause phase, some women experience a sexual resurgence and appreciate the freedom from menstrual cycles and contraceptives in menopause [19]. Support from other women and the ability to share stories can help women bond and deal with the changes they experience [18]. The National Women’s Health Information Center finds that society’s and women’s ideas about menopause might become more nuanced if more women were vocal about their menopause experience [18]. 

Peer to Peer Advice

  1. Try herbal supports, but check with your doctor before starting any supplements. Try Melissa Lemon Balm, which showed improved sexual function after menopause [See the Sexual Function chapter][20]. 
  2. Experiment with different lubricants that are glycerine, paraben and petrochemical free to help with vaginal dryness, tearing and dyspareunia [See the Sexual Function chapter]
  3. Consider treatments for vaginal rejuvenation using energy-based nonsurgical procedures on vaginal tissue that have been used to improve vaginal dryness or vaginal atrophy (thinning of the vaginal wall) during perimenopause or postmenopause. You should find a qualified healthcare physician for this treatment. Cleveland Clinic information on energy based treatments and vaginal rejuvenation.
  4. Consider vaginal dilator therapy that can be used at home to stretch the vagina because vaginal atrophy is associated with menopause. However, a recent study showed that there were no clinically proven standardized protocols or formalized guidelines to give to patients about how to best use their dilators. Larger long-term future studies are required to assess effectiveness [21]. Consult your gynecologist or urologist for more information.
  5. Find a network of perimenopausal and menopausal women who share their experiences, which can be helpful [18].
  6. Seek information to cope with menopause. The National Women’s Health Information Center has a section on menopause and perimenopause [18]. The North American Menopause Society (NAMS) is another option.
  7. Remembering that menopause is a normal physiological life transition can help women cope and view some changes as positive [18].

Works Cited

  1. Mayo Clinic. Menopause: Symptoms and causes. https://www.mayoclinic.org/diseases-conditions/menopause/symptoms-causes/syc-20353397. Website. Accessed 9.23.2020.
  2. Newson LR. Best practice for HRT: Unpicking the evidence. The British journal of general practice : the journal of the Royal College of General Practitioners. 2016;66(653):597-598. https://search.proquest.com/docview/1844024861.
  3. Agarwal S, Alzahrani FA, Ahmed A. Hormone replacement therapy: Would it be possible to replicate a functional ovary? International journal of molecular sciences. 2018;19(10):3160. https://www.ncbi.nlm.nih.gov/pubmed/30322209. doi: 10.3390/ijms19103160.
  4. Real FG, Svanes C, Omenaas ER, et al. Lung function, respiratory symptoms, and the menopausal transition. Journal of allergy and clinical immunology. 2008;121(1):72-80.e3. https://search.datacite.org/works/10.1016/j.jaci.2007.08.057. doi: 10.1016/j.jaci.2007.08.057.
  5. Cyganek A, Pietrzak B, Wielgoś M, Grzechocińska B. Menopause in women with chronic immunosuppressive treatment – how to help those patients. Przegla̜d menopauzalny. 2016;15(1):1-5. https://www.ncbi.nlm.nih.gov/pubmed/27095951. doi: 10.5114/pm.2016.58765.
  6. Cystic Fibrosis Foundation. Adult guide to cystic fibrosis. n.d. https://www.cff.org/life-with-cf/daily-life/adult-guide-to-cf.pdf.
  7. Bromberger JT, Epperson CN. Depression during and after the perimenopause: Impact of hormones, genetics, and environmental determinants of disease. Obstetrics and gynecology clinics of North America. 2018;45(4):663-678. https://www.ncbi.nlm.nih.gov/pubmed/30401549. doi: 10.1016/j.ogc.2018.07.007.
  8. Triebner K, Matulonga B, Johannessen A, et al. Menopause is associated with accelerated lung function decline. American journal of respiratory and critical care medicine. 2017;195(8):1058-1065. https://search.datacite.org/works/10.1164/rccm.201605-0968oc. doi: 10.1164/rccm.201605-0968oc.
  9. Karlamangla, Arun S., PhD, MD, Burnett-Bowie, Sherri-Ann M., MD, MPH, Crandall, Carolyn J., MD, MS. Bone health during the menopause transition and beyond. Obstetrics and Gynecology Clinics. 2018;45(4):695-708. https://www.clinicalkey.es/playcontent/1-s2.0-S088985451830072X. doi: 10.1016/j.ogc.2018.07.012.
  10. Fait T. Menopause hormone therapy: Latest developments and clinical practice. Drugs in Context. 2019;8:1-9. https://search.datacite.org/works/10.7573/dic.212551. doi: 10.7573/dic.212551.
  11. Shumaker SA, Legault C, Rapp SR, et al. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: The women’s health initiative memory study: A randomized controlled trial. JAMA : the journal of the American Medical Association. 2003;289(20):2651-2662. http://dx.doi.org/10.1001/jama.289.20.2651. doi: 10.1001/jama.289.20.2651.
  12. Shumaker SA, Legault C, Kuller L, et al. Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women’s health initiative memory study. JAMA : the journal of the American Medical Association. 2004;291(24):2947-2958. http://dx.doi.org/10.1001/jama.291.24.2947. doi: 10.1001/jama.291.24.2947.
  13. National Cancer Institute. MHT fact sheet. https://www.cancer.gov/about-cancer/causes-prevention/risk/hormones/mht-fact-sheet. Website. 
  14. Women’s Health Initiative Study Group. Design of the women’s health initiative clinical trial and observational study. Control Clin Trials. 1998;19(1):61-109. http://www.sciencedirect.com.proxy.cc.uic.edu/science/article/pii/S0197245697000780. doi: 10.1016/S0197-2456(97)00078-0.
  15. Anderson GL, Judd HL, Kaunitz AM, et al. Effects of estrogen plus progestin on gynecologic cancers and associated diagnostic procedures: The women’s health initiative randomized trial. JAMA : the journal of the American Medical Association. 2003;290(13):1739-1748. http://dx.doi.org/10.1001/jama.290.13.1739. doi: 10.1001/jama.290.13.1739.
  16. Chlebowski RT, Kuller LH, Prentice RL, et al. Breast cancer after use of estrogen plus progestin in postmenopausal women. The New England Journal of Medicine. 2009;360(6):573-587. https://search.datacite.org/works/10.1056/nejmoa0807684. doi: 10.1056/NEJMoa0807684.
  17. Heiss G, Wallace R, Anderson GL, et al. Health risks and benefits 3 years after stopping randomized treatment with estrogen and progestin. JAMA : the journal of the American Medical Association. 2008;299(9):1036-1045. http://dx.doi.org/10.1001/jama.299.9.1036. doi: 10.1001/jama.299.9.1036.
  18. Emily Vaughn. Menopause can start younger than you think: Here’s what you need to know. Shots [BLOG] Web site. https://search.proquest.com/docview/2342353757. Updated 2020.
  19. The North American Menopause Society. Changes at mid-life. https://www.menopause.org/for-women/sexual-health-menopause-online/changes-at-midlife.
  20. Darvish-Mofrad-Kashani Z, Emaratkar E, Hashem-Dabaghian F, et al. Effect of melissa officinalis (lemon balm) on sexual dysfunction in women: A double- blind, randomized, placebo-controlled study. Iranian journal of pharmaceutical research: IJPR. 2018;17(Suppl):89-100. https://www.ncbi.nlm.nih.gov/pubmed/29796033.

21. Liu M, Juravic M, Mazza G, Krychman ML. Vaginal dilators: Issues and answers. Sexual Medicine Reviews. 2020. http://dx.doi.org/10.1016/j.sxmr.2019.11.005. doi: 10.1016/j.sxmr.2019.11.005.

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