Challenges to medication adherence for morbidities during menopause

• The significant milestone of menopause is associated with the risk of weight gain, poor bone health, chronic diseases, and cancers^{1,6,9, 11, 12}
• Medication adherence during menopause is poor. The primary barriers are enhanced menopause symptoms and multimorbidity fuelled by poor psychological health^{17, 20, 24.}

Risk of morbidities during menopause

Menopause is a natural and among the first manifestation of the aging process in women marking an end of the fertility period. It is a multidimensional physiological transition as ovaries reduce their function resulting in receding levels of female sex hormones – estrogen and progesterone. The accompanying physical and psychological changes result in well-known physical discomforts. As women transit through this stage of life, they also become susceptible to other age-associated health concerns like unintended weight gain, poor bone health, chronic diseases, and cancers. This article describes these comorbidities and the challenges women face in adhering to their treatment during menopause.

Weight-gain: Unhealthy weight gain especially adipose deposition/redistribution in the central or visceral region is common in menopausal women, likely due to hormonal changes and increasing age, lower physical activity, and chronic health conditions1. According to an American survey on peri- and post-menopausal (40-59 year old) women 68% were found to be obese. The risk of obesity is higher in women undergoing unnatural menopause due to the removal of either ovaries or uterus or both as compared to premenopausal/early-perimenopausal women2. Importantly, obesity provides the basic framework for other chronic diseases to develop putting menopausal women at higher risk for diabetes and cardiovascular diseases^3,4.

Urinogenital complications: Pelvic floor disorders, urinary incontinence, and incidence of urinary tract infections (UTI) increase in women undergoing menopause⁵. Lower estrogen levels result in an altered urobiome and disruption of the urothelial barrier is favorable for the growth of “bad” bacteria causing recurrent UTIs that require repeated antibiotic treatments. Similarly, declining estrogen levels may reduce the strength of pelvic floor muscles, contributing to the occurrence of urinary incontinence in menopausal women⁵.

Cardiovascular diseases (CVD): Studies point toward a higher risk of cardiovascular diseases post-menopause⁶. Increase in CVD could be due to changes in risk factors as women transition through menopause, due to both menopause and chronological aging-associated factors. Lower estradiol (E2) and higher follicle-stimulating hormone (FSH) during menopause are associated with atherosclerosis⁷. The relative CVD risk is higher in women experiencing an early onset of menopause (aged <45 years), either due to natural causes or surgical removal of ovaries⁶. If initiated at the right time, the estrogenic component from HRT exerts an early beneficial effect on healthy endothelium. It leads to a reduction in the risk of coronary heart disease (RR 0.52, 95% CI 0.29 to 0.96) and overall mortality (RR 0.70, 95% CI 0.52 to 0.95) when started in women between 50-60 years or within 10 years after the menopause onset⁸.

Type-2 diabetes mellitus (T2DM): Menopause as an independent risk factor of diabetes is a matter of contention. . Change in the hormonal landscape leads to a relative increase in androgenicity, insulin resistance, sleep disorders, mood fluctuations, and weight gain during menopause increases the risk of T2DM9,10  All these factors are associated with elevated blood glucose and insulin resistance¹⁰.

Poor Bone health: Females start losing bone density gradually from the age of 30 years. However, it nose-dives during menopause transition. The rapid loss of bone mass begins a year before the final menstrual period and continues to decline for the next two years, before plateauing; resulting in adverse changes in bone macrostructure and microarchitecture. The loss of bone density is also associated with reduced estrogen levels increasing osteoporosis and fracture risk in older women¹¹.

Cancers: Unhealthy BMI in women approaching menopause is a high-risk factor for developing breast cancer. Women with higher BMI have 2-fold higher levels of estrogens and also higher levels of circulating estrogens which increases the risk of breast cancer¹². The risk of ovarian cancer is also higher in post-menopausal women with a reproductive history of miscarriages, stillbirth, and higher age during the first gestation¹³. While the cancer risk is shown to be higher with the use of hormone replacement therapy (HRT) for menopause symptoms, users shall consider that not all treatments are the same and may impact differently the risk of endometrial and breast cancer^14,15.

Medication adherence concerns for comorbidities during menopause

Medication adherence is of foremost importance to achieve the expected efficacy of a treatment therapy in the “real-world” clinical practice. Failure to adhere causes avoidable health complications and is a significant medical and financial burden16. For more information on the impact of menopause on women’s life, please refer to our article Menopause’s impact on women’s lives and adherence to treatment during the peri- and post-menopausal period.

Listed below are reasons for non-adherence to treatment for comorbidities during menopause:

• Menopausal symptoms: The complex physiological changes during menopause result in varied symptoms and form an important barrier to medication adherence (as discussed in a previous article in this series- Menopause’s impact on women’s lives and adherence to treatment during the peri- and post-menopausal period). A common reason for poor adherence to breast cancer treatment in menopause is the enhancement of menopausal symptoms due to the therapy-mediated lowering of sex hormones¹⁷. Similarly, women with HIV report challenges in adhering to retroviral therapy due to an increase in the severity of menopause symptoms¹⁸. Adherence to bisphosphonates prescribed for osteoporosis treatment in menopause is suboptimal due to enhanced side effects¹⁹.
• Multimorbidity: Menopausal women are likely to suffer from more than one health issue²⁰. The adherence rate is known to be poor for multimorbidities employing complex drug regimens and is inversely proportional to the number of medications prescribed. Lifestyle changes are foremost for chronic diseases and are often not adhered to by middle-to-old aged patients.
• Socio-demographic factors: Older adults have enhanced difficulty in adhering to the prescribed therapy. A clinical trial reported failure in understanding the written health information in the majority of women participants resulting in non-adherence to their medications²¹. Low education level is also an important factor for false illness perceptions and causes difficulties in making appointments, accessing prescriptions, and requesting prescription refills as well. Studies have also highlighted gender-specific differences in medication adherence. Also, there exists a gender bias in medication development that could result in higher side effects experienced by female patients22. Older females are also more likely to face financial barriers in accessing healthcare and medications due to inadequate health insurance or dependence on other family members²³. Additionally, a social support network is essential for treatment adherence. Menopausal women find themselves in want of social support as they deal with the death of elderly parents, empty-nest syndrome, and separation from a long-time partner due to divorce or death.
• Psychological issues: Lower sex hormones adversely influence mental health during menopause, elevating stress, anxiety, irritability, and depression²⁴. Poor mental health clouds the rational-decision making process (See – Two systems of thinking: Why do rational people make irrational choices) and is associated with forgetfulness, an unhealthy lifestyle, and suboptimal treatment adherence.
• Healthcare-associated factors: Healthcare practitioners and other healthcare resources are important determinants of medication adherence (See- Healthcare practitioners: a potential springboard to success in medication adherence). Effective communication about drug regimens, dosage, and potential adverse effects is often lacking during healthcare visits21. The stigma associated with menopausal symptoms impedes effective communication between the provider and the patient.

Conclusion

The reasons for non-adherence to treatments during menopause are varied and complex, therefore the solutions should also be multifactorial. Medications that enhance the menopausal symptoms need to be carefully discussed and possibilities of alternative therapies should be explored to enhance adherence. Importantly, diagnosis and appropriate treatment of menopausal symptoms will help alleviate the non-adherence due to drug side effects in chronic diseases. Finally, compassionate communication with the HCP/pharmacists will help women struggling with the lack of social support and have the potential to enhance medication adherence21.

Sometimes you will be in control of your illness and other times you’ll sink into despair, and that’s OK! Freak out, forgive yourself, and try again tomorrow.”
— Kelly Hemingway