Menopause

The healthyher.life team supports a holistic approach to managing women’s hormonal healthcare. Our goal is to help our members be well-informed about their hormonal health, by providing them with evidence-based integrated health information that includes the current standard of medical care advised by qualified physicians, clinical insights from licensed allied health professionals (naturopathic doctors, nurse-practitioners, nutritionists, psychotherapists) and new health innovations that will be soon coming to market. Always consult with your doctor regarding your medical condition, diagnosis, treatment, or to seek personalized medical advice.

Got a question about Menopause?

Introduction to Menopause

Reviewed by Rina Carlini, PhD and Joanne Tejeda, PhD
May 16, 2023

Menopause is a natural physiological transition experienced by all women, and individuals assigned female at birth. The menopause transition will span about 5-8 years for most women between the ages of 45-55 years, but it can naturally start as early as age 40 or end as late as age 60. The term 'menopause' is clinically determined as the date which is 12 months after your last menstrual cycle. As the levels of a woman's natural reproductive hormones decline - which include estrogen (present in the body as estradiol) and progesterone decline - these changing levels lead to reduced function of the ovaries to produce egg cells (ova), and result in halting menstruation.

Menopause is categorized in 3 stages:

Stage 1 - Perimenopause: a transition period associated with the onset of fluctuating reproductive hormones and associated symptoms (see partial list below) which typically lasts from 1 to 5 years (however it can span a longer period of up to 10 years for some women).
Stage 2 - Menopause: the date that represents 12 consecutive months with no menstrual cycle, following your last menstruation period.
Stage 3 - Post-menopause: the period that following the menopause date, which is the rest of your adult life; symptoms will typically get milder and be manageable, and for some women, may even disappear.

Menopause is not a disease but rather a natural hormonal transition. However, the physiological changes that accompany the menopause transition can give rise to serious health conditions that require ongoing medical care - these include:

Cardiovascular diseases such as hyperlipidemia (elevated cholesterol) and arrhythmia
Osteoporosis
Type II diabetes
Colorectal cancer

For some women, and individuals assigned female at birth, a surgery to remove the reproductive organs including ovaries and/or uterus (as in the case of partial or total hysterectomies) can trigger menopause abruptly, which is referred to as premature menopause.

Symptoms

There have been more than 30 'symptoms' or signs of perimenopause reported in teh clinical literature, which may be experienced by individuals - a partial list is provided below:

Vasomotor symptoms such as hot flashes and/or night sweats (the most reported symptom)
Irregular menstrual cycles - these can be light or heavy periods
Heavy prolonged menstrual bleeding
Vaginal dryness - experienced during intercourse, and sometimes also with walking
Painful intercourse
Sleep disturbances
Alcohol intolerance
Frequent urination, frequent flatulence
Frequent urinary tract infection (UTIs)
Moodiness and irritability
Depression and/or anxiety
Heart palpitations, and decreasing heart rate
Weight gain
Increasing waist size
Hair thinning or hair loss
Dry hair texture, more grey/white hair growth
Dry flaky skin, dull or hyperpigmented skin
Acne, rosacea, and other skin blemishes
Weakened muscle strength
Joint aches and pains with regular movement

Treatment Options

Symptom management for menopause needs to be personalized, and can include a combination of drug and non-drug options along with lifestyle changes, such as:

Hormone therapies:

Estrogen supplementation (Menopausal Hormone Therapy, MHT)
Progesterone-based therapeutic agents
Synthetic steroids that mimic progesterones and/or estrogens

Non-hormonal therapies: (see article below)

Low-dose paroxetine
Gabapentin
Fezolinetant
Venlafaxine
Herbal remedies, such as chasteberry

Lifestyle changes:

Regular exercise and weight-bearing strengthening exercise
Good protein-based nutrition for managing weight and heart health
Psychotherapy, if you experience ongoing depression and/or anxiety
Water-based lubricants and vaginal moisturizers to counteract dryness and vaginal pain with intercourse (symptoms of GSM, genitourinary syndrome of menopause)
Regular sleep routines, meditation, and relaxation techniques
Naturopathic solutions, such as vitamin supplementation
Limiting caffeine (1-2 cups of coffee per day) and alcohol (1 beverage per week)

The transition through all stages of menopause occurs very slowly, lasting up to 8 years, and in some cases, symptoms can last up to 10 years after menopause. The menopause transition is an inevitable progression of aging in women, and about 75% of all women experience life-disrupting symptoms of menopause. Being proactive about this natural phase of life is key to minimizing these disruption and living a healthyher life.

Below are a collection of articles that address the specific symptoms of perimenopause transition, which ends with menopause (the date when a women's menstruation has stopped for a full 12 months). We hope they are helpful when you ask questions with a women's healthcare professional who is trained as a Menopause Society Certified Professional (MSCP).

Healthyher.Life is your hormonal healthcare navigator platform, which offers trusted, evidence-based hormonal health solutions, personalized support with Hailey™, Your AI Health Concierge™, fast access to a telehealth physician consult, a Marketplace of quality-assured health and wellness products, and access to our Community Forum to connect and chat with a global community of members.

Hormones and Esthetics, Part 1: How Hormonal Conditions Can Affect Skin Health For Women

By Susan Johnson, MD candidate
Reviewed by Aditi Das, PhD and Rina Carlini, PhD
March 14, 2025

Woman skin health mirror_edited_edited.j

Image Source: Shutterstock ID# 2415677219

Your skin can reveal a lot about what’s happening inside your body. Produced by the endocrine glands, hormones are chemical messengers that impact how your skin looks and feels.

As women go through different life stages like puberty, menstruation, pregnancy, perimenopause and post-menopause, hormone levels rise and fall, often bringing noticeable changes to the skin. In addition, conditions like polycystic ovary syndrome (PCOS) and endometriosis can throw hormones off balance, leading to issues like acne, dryness, or pigmentation.

The Relation Between Hormone Imbalances And Skin Health

If you have wondered why your skin goes through stages of dewy radiance to sudden breakouts, hormones are likely responsible. While a few pimples or occasional dullness might not be a big deal, some hormonal imbalances can cause more stubborn skin problems.

Estrogen

The skin is made up of a foundation called the extracellular matrix (ECM), which contains molecules like collagen, elastin, and hyaluronic acid. All these substances have estrogen receptors on them, which means they are influenced by the estrogen levels in your body. [1]

When estrogen production declines during menopause, your skin starts to change in noticeable ways.

Wrinkles and Volume Loss – Produced by cells called fibroblasts, collagen keeps the skin plump and youthful. When estrogen levels fall, collagen production slows down, leading to fine lines, wrinkles, and sagging. According to studies, women lose about 30% of collagen during the first five years of menopause. [2]

Sagging – Elastin makes your skin bouncy, flexible, and taut. A lack of estrogen causes the elastin fibers to become thicker and clump together. So your skin becomes less firm and more prone to sagging.

Figure 1: In aged skin, decreased estrogen levels lead to reduced collagen and elastin production. (Image Source: Health Matters

Dryness and Itching– Glycosaminoglycans (GAGs) such as hyaluronic acid are natural components in the skin that help retain water, keeping the skin hydrated and plump. Low estrogen levels decrease GAG production, leading to dry, dehydrated skin. This decline in GAGs also weakens the skin's elasticity, leading to increased dryness, itchiness, and sensitivity, making the skin more prone to irritation.
Uneven Skin Tone (Melasma) – Estrogen plays a key role in regulating melanocyte function, which is responsible for maintaining an even skin tone. As estrogen levels drop, melanocyte activity may decrease, leading to uneven pigmentation, blotchiness, or a duller complexion, especially in areas exposed to the sun. Women of color are found to be more prone to developing hyperpigmentation during menopause. A cross-sectional analysis of the All of Us database found Hispanic and Asian individuals to exhibit a threefold higher prevalence compared to White and Black populations, with the highest occurrence among those aged 41–55. [3]
Thinning – A fall in estrogen levels decreases blood flow to the dermal vascular system, thereby inhibiting the formation of new blood vessels. Lack of nourishment makes the skin thinner, so it bruises more easily. The veins and bony landmarks also become easily visible on thin skin.
Longer Healing Time –Estrogen levels also influence repair enzymes and growth factors such as epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF), which play key roles in skin cell regeneration and wound healing. A decrease in estrogen can lead to reduced activity of these factors, making the skin more fragile and impairing its ability to heal wounds effectively.
Flushing – Declining estrogen levels disrupt your body's temperature regulation system, leading to hot flashes. It is characterized by sudden sensations of heat, sweating, and a rapid heartbeat, with each episode lasting anywhere from 2 to 30 minutes. The clinical evidence indicates that approximately 75% to 80% of menopausal women in the U.S. experience hot flashes. [4]

Progesterone

Progesterone stimulates the sebaceous glands on your skin to produce sebum or oil and keeps your skin supple. Changes in progesterone levels can cause:

Acne – Progesterone levels rise during the second half of the menstrual cycle, often leading to oily skin, clogged pores, and acne, especially around the jawline.
Puffiness and Swelling – Progesterone helps retain moisture by improving the skin barrier function, making your skin plump and hydrated. However, rising hormone levels can lead to water retention, leading to puffiness and swelling. [5]
Drying and Dullness – When the production of progesterone drops during menopause, the skin may become dry, rough, and less radiant. [6]

Testosterone

Though testosterone is usually associated with men, women produce small amounts of this hormone. [7] Testosterone has a mechanism similar to that of progesterone–it stimulates the sebaceous glands to produce oil.

Just like progesterone, when testosterone production increases after ovulation [8] or in conditions like PCOS and endometriosis, it can result in excessive sebum production and clog pores, creating an ideal environment for acne-causing bacteria to thrive, leading to breakouts, especially in the T-zone (forehead, nose, and chin). Conversely, a drop in testosterone levels during menopause can lead to skin dryness.

Cortisol

The body’s primary stress hormone, cortisol, triggers oil production in the sebaceous gland. [9]

Acne – During menopause, the cortisol level spikes, causing clogged pores, breakouts, or exacerbating existing acne.
Aging – High cortisol levels also accelerate skin aging (wrinkles, sagging, and dull complexion) by breaking down collagen fibers.

Cortisol spikes can also worsen inflammatory skin conditions like psoriasis, eczema, or rosacea, leading to redness, flare-ups, and slower healing. [10] According to studies, chronic urticaria (hives) and psoriasis were found to be more prevalent in women with endometriosis than in women without the disease. [11] Lichen sclerosus is a chronic inflammatory skin condition primarily affecting postmenopausal women. It causes painful, patchy, discolored, and thin skin, particularly around the genital and anal areas. Additionally, it is also seen in women with endometriosis.

To learn more about how chronic stress impacts your hormones, contributing to concerning health issues in mid-life women, stay tuned for our upcoming feature articles on these topics.

Thyroid Hormones

Thyroxine (T3) and triiodothyronine (T4) play a vital role in regulating your body’s metabolism, skin cell turnover, and moisture retention, all of which impact skin health. [12] Any changes to thyroid hormone levels can trigger changes in the skin’s overall appearance.

Dry, Rough, and Flaky Skin – Hypothyroidism is a common problem faced by women going through menopause. According to studies, nearly 12-20% of women over the age of 60 years are thought to have an underactive thyroid. [13] Since the thyroid gland regulates the activity of oil and sweat glands, dropping levels of thyroid hormones can lead to dryness, flakiness, and irritation. [14]
Warm, Sweaty Skin – On the other hand, hyperthyroidism makes the skin oily, warm, and sometimes flushed. Due to increased cell turnover, the skin may also become thin, delicate, and more prone to bruising. [15]

How To Keep Your Skin Healthy Amid Hormonal Changes?

While you must discuss any new skin changes with your doctor or dermatologist, there are some general lifestyle changes you can make to maintain your skin health through hormonal transitions.

Consume a balanced diet rich in antioxidants, vitamins, and minerals to reduce oxidative stress and support collagen production.
Avoid alcohol, caffeine, and spicy food, as they can trigger hot flashes and worsen skin issues, particularly during hormonal changes.
Drink plenty of water to keep your skin hydrated and maintain its elasticity.
Practice stress-relief techniques like yoga, meditation, etc., to reduce cortisol spikes that can contribute to acne and skin inflammation.
Exercise regularly to improve blood flow to the skin.
Aim for 7-9 hours of quality sleep every night to reduce dullness and promote skin repair.
Avoid long, hot showers that dry out the skin.
Apply a broad-spectrum sunscreen with a high SPF (above 30) every day to prevent hyperpigmentation and premature aging.
Opt for gentle, non-soap based cleansers to avoid skin irritation and dryness and to lessen sensitive skin conditions.
Moisturize your skin twice a day, ideally with a moisturizer containing hyaluronic acid or glycerin to maintain hydration and reduce fine lines.
Incorporate skincare products containing ingredients like retinol or peptides, as they can stimulate collagen production in your skin, helping reduce wrinkles and improve skin texture.

While these measures can help manage skin changes, finding the right products can often be overwhelming. It’s best to consult a board-certified dermatologist, endocrinologist or gynecologist for a personalized treatment plan, which may include hormonal therapies, steroid creams, oral medications, or topical agents. Always consult your doctor for optimal efficacy and safety.

Hormone Therapy – Estrogen, progesterone, or a combination of both is prescribed to replace the hormones that your body produces less of. By bringing the hormone levels back to pre-perimenopause levels, hormone therapy has been found to increase dermal collagen levels and improve skin thickness and elasticity. [16]
Topical Estrogens – Available as gels or creams, topical estrogen is used to treat moderate to severe symptoms of menopause, such as hot flashes, vaginal dryness and itching, etc.
Selective Estrogen Receptor Modulators (SERMs) – These compounds act as estrogen agonists in the skin and show promise in improving skin health. In a 12-week clinical study, women applying topical equol twice daily experienced significant improvements in skin firmness and hydration. [17]

If you have concerns about any skin issue, always consult with your family doctor or a licensed physician to get an accurate assessment, diagnosis and treatment plan that is right for you.

Healthyher.Life is your hormonal healthcare navigator platform offering you trusted, evidence-based hormonal health solutions, personalized support with Hailey™, Your AI Health Concierge™; faster access to a telehealth physician consult; a Marketplace of quality-assured health and wellness products; and access to our Community Forum to connect and chat with a global community of members.

Other Recommended Menopause Resources

The Menopause Society (formerly the North American Menopause Society)

Find A Certified Menopause Practitioner

Canadian Menopause Society

Menopause Quick 6 (#MQ6)

The Australasian Menopause Society

Menopause Preparedness Toolkit: A Woman’s Empowerment Guide

Impact of Menopause Symptoms on Women in the Workplace, submitted by Stephanie Faubion, MD, MBA, Mayo Clinic

The M Factor: Shredding the Silence on Menopause

Depression & Menopause Coinciding for Midlife Women: Know the Symptoms and Treatment Options

By Susan Johnson
Reviewed by Rina Carlini, PhD
November 19, 2024

Image Source: Shutterstock (ID: 1878919180)

Depression is a significant mental health concern, affecting around 280 million people in the world–most of them women. [1] In most women, the risk of experiencing depression spikes in midlife (ages 45 to 54), with about 20-30% facing first or recurrent episodes of major clinical depression during this time. [2] While concerns about aging, dealing with workplace issues, and challenges in intimate relationships are a few reasons to blame, menopause is another crucial factor.

The transition to menopause is accompanied by notable psychological changes, such as mood swings and anxiety, in nearly one in three women. Even women with no prior history of depression are two to four times more likely to experience depressive symptoms during perimenopause than their younger or older counterparts. [3]

The Menopausal Transition

According to the American College of Obstetricians and Gynecologists (ACOG), menopause is the time when a woman’s menstrual periods stop permanently following 12 consecutive months of no periods.[4]

The period leading up to menopause is called perimenopause, which can span a period of 3-7 years on average. During this time, the hormone levels, particularly estrogen, begin to decline, causing irregular menstrual cycles and symptoms like hot flashes, insomnia, anxiety, mood swings, and depressive feelings.

Depressive symptoms during the menopause transition can manifest in several ways:

Fatigue or low-energy
Irritability, restlessness, or agitation
Difficulty concentrating or making decisions
Persistent sadness or feeling of emptiness
Sleep disorders, such as insomnia or oversleeping
Loss of interest in activities once enjoyed
Feelings of worthlessness or guilt
Changes in appetite or weight
Suicidal thoughts

Most women get relief from depressive symptoms in the post-menopause years, but some may continue to experience mood disturbances. This could be due to poor social support, unaddressed mental health concerns, substance abuse, and others.

Are Hormones The Only Thing To Blame?

In the past, researchers have studied the association between mood changes and hormones like follicle-stimulating hormone (FSH) and estradiol. The results were inconsistent, with some studies linking higher levels of these hormones to increased depressive symptoms while others not confirming this connection.

During perimenopause, the estrogen and progesterone levels start to fall. Since estrogen acts as a protective agent in the brain, a decline in estrogen levels plays a crucial role in increasing the risk of developing depression, particularly in those who have suffered major depression in the past. Estrogen also impacts serotonin transmission (a neurotransmitter that promotes feelings of happiness) by influencing serotonin receptor expression. When the estrogen levels fall, it disrupts serotonin balance, potentially destabilizing moods and leading to irritability, anxiety, and sadness. [5]

Changes in the transmission of other neuropeptides, such as dehydroepiandrosterone sulfate (DHEAS) and gamma-aminobutyric acid (GABA), may also happen during perimenopause and can cause depressive symptoms. Lower levels of DHEAS and GABA in older women have been associated with increased symptoms of depression, similar to those seen in major depressive disorders. [6] [7]

Beyond hormonal changes, studies have also shown two major risk factors–biological and psychological–that shape a woman’s experience during menopause. Biological risk factors include hot flashes, night sweats, sleep disturbances, and unrelated chronic medical conditions. For instance, hot flashes occur as a result of the dysregulation in the brain’s thermoregulatory center due to ovarian failure and estrogen loss. It can lead to poor sleep quality, making women feel low and anxious and, ultimately, depressed. [8] Sleep disturbances and chronic health conditions can also add stress, which increases the likelihood of experiencing mood changes.

A history of depression/ postpartum depression, an adverse perception of menopause, and higher levels of neuroticism—a personality trait associated with negative emotions–are psychological factors that are strongly related to depressive symptoms during the menopause transition. [9]

Lastly, additional life challenges such as relationship conflicts, caregiver responsibilities, career transitions or job demands, financial stress, retirement planning, or even kids moving out can contribute to feeling depressed and anxious during menopause.

How Is Menopausal Depression Managed/ Treated?

Current guidelines recommend treating menopausal depression with a combination of antidepressants like selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), psychological therapy, and lifestyle changes. [10] However, antidepressants may not work for everyone and can cause side effects like serotonin syndrome, emotional numbness, diarrhea, agitation, nausea, anorexia, excessive sweating, insomnia, headache, decreased libido, etc. [11] For example, some menopausal women with

significant insomnia, irritability, or anxiety may not respond well to common SSRIs like escitalopram, or they might experience an exacerbation of symptoms with fluoxetine. For this reason, the choice of antidepressants should be tailored for each woman.

Newer medications, like desvenlafaxine (an SNRI) and agomelatine, have shown promise for perimenopausal women, with agomelatine proving to help treat insomnia. [12] [13] [14]

When it comes to psychosocial treatment, it is effective in women with perimenopausal depression that stems from work or relationship stresses common in midlife. In addition, exercise, mindfulness techniques, yoga, and dietary adjustments are also helpful in managing symptoms of depression to some extent.

According to the data so far, menopausal hormone therapy (MHT) has shown promise in treating mild perimenopausal depression linked to hormonal fluctuations, but its effectiveness for postmenopausal depression remains unclear. [15] Recently, newer MHT regimens like low-dose hormones and transdermal estradiol, which can cross the blood-brain barrier, are also being explored. [16]

However, MHT is not suitable for women with a history of hormone-dependent cancers or venous thromboembolism. The Australasian Menopause Society (AMS) has evidence-based guidelines that healthcare providers should follow when prescribing MHT. [17] [18]

How effective are lifestyle changes such as meditation, exercise and choice of diet?

Hormonal treatments are not generally prescribed for women who smoke, have high blood pressure, have a history of blood clotting, have heart or liver diseases, have conditions like diabetes or epilepsy or are already postmenopausal.

For these patients, lifestyle adjustments are recommended, such as adopting a balanced diet [19], practicing meditation, exercising regularly, and limiting caffeine and alcohol intake. These strategies can promote mental well-being and significantly ease perimenopausal symptoms. While these adjustments may alleviate symptoms, they cannot fully resolve the major depressive disorder and should be combined with medication and/or psychological therapy for the best outcomes.

References:

[1] World Health Organization: WHO & World Health Organization: WHO. (n.d.). Depressive disorder (depression). https://www.who.int/news-room/fact-sheets/detail/depression

[2] Colvin A, Richardson GA, Cyranowski JM, Youk A, Bromberger JT. Does family history of depression predict major depression in midlife women? Study of Women's Health Across the Nation Mental Health Study (SWAN MHS). Arch Womens Ment Health. 2014 Aug;17(4):269-78. doi: 10.1007/s00737-014-0433-8. Epub 2014 Jun 21. PMID: 24952069; PMCID: PMC4120816.

[3] Bromberger JT, Kravitz HM, Chang YF, Cyranowski JM, Brown C, Matthews KA. Major depression during and after the menopausal transition: Study of Women's Health Across the Nation (SWAN). Psychol Med. 2011 Sep;41(9):1879-88. doi: 10.1017/S003329171100016X. Epub 2011 Feb 9. Erratum in: Psychol Med.2011 Oct;41(10):2238. PMID: 21306662; PMCID: PMC3584692.

[4] The menopause years. (n.d.). ACOG. https://www.acog.org/womens-health/faqs/the-menopause-years

[5] Freeman EW, Sammel MD, Lin H, Nelson DB. Associations of Hormones and Menopausal Status With Depressed Mood in Women With No History of Depression. Arch Gen Psychiatry. 2006;63(4):375–382. doi:10.1001/archpsyc.63.4.375

[6] Morrison MF, Ten Have T, Freeman EW, Sammel MD, Grisso JA. DHEA-S levels and depressive symptoms in a cohort of African American and Caucasian women in the late reproductive years. Biol Psychiatry. 2001 Nov 1;50(9):705-11. doi: 10.1016/s0006-3223(01)01169-6. PMID: 11704078.

[7] Wang Z, Zhang A, Zhao B, Gan J, Wang G, Gao F, Liu B, Gong T, Liu W, Edden RA. GABA+ levels in postmenopausal women with mild-to-moderate depression: A preliminary study. Medicine (Baltimore). 2016 Sep;95(39):e4918. doi: 10.1097/MD.0000000000004918. PMID: 27684829; PMCID: PMC5265922.

[8] Freeman EW, Sammel MD, Lin H. Temporal associations of hot flashes and depression in the transition to menopause. Menopause. 2009 Jul-Aug;16(4):728-34. doi: 10.1097/gme.0b013e3181967e16. PMID: 19188849; PMCID: PMC2860597.

[9] Ormel J, Jeronimus BF, Kotov R, Riese H, Bos EH, Hankin B, Rosmalen JGM, Oldehinkel AJ. Neuroticism and common mental disorders: meaning and utility of a complex relationship. Clin Psychol Rev. 2013 Jul;33(5):686-697. doi: 10.1016/j.cpr.2013.04.003. Epub 2013 Apr 29. PMID: 23702592; PMCID: PMC4382368.

[10] Managing menopausal symptoms. (n.d.). https://ranzcog.edu.au/wp-content/uploads/Managing-Menopausal-Symptoms.pdf

[11] Ma H, Cai M, Wang H. Emotional Blunting in Patients With Major Depressive Disorder: A Brief Non-systematic Review of Current Research. Front Psychiatry. 2021 Dec 14;12:792960. doi: 10.3389/fpsyt.2021.792960. PMID: 34970173; PMCID: PMC8712545.

[12] Soares CN, Thase ME, Clayton A, Guico-Pabia CJ, Focht K, Jiang Q, Kornstein SG, Ninan PT, Kane CP. Open-label treatment with desvenlafaxine in postmenopausal women with major depressive disorder not responding to acute treatment with desvenlafaxine or escitalopram. CNS Drugs. 2011 Mar;25(3):227-38. doi: 10.2165/11586460-000000000-00000. PMID: 21323394.

[13] Kornstein SG, Jiang Q, Reddy S, Musgnung JJ, Guico-Pabia CJ. Short-term efficacy and safety of desvenlafaxine in a randomized, placebo-controlled study of perimenopausal and

postmenopausal women with major depressive disorder. J Clin Psychiatry. 2010 Aug;71(8):1088-96. doi: 10.4088/JCP.10m06018blu. PMID: 20797382.

[14] S. Krüger, T. Tran, EPA-1061 – Agomelatine in the treatment of perimenopausal depression - a pilot study, European Psychiatry, Volume 29, Supplement 1, 2014, Page 1, ISSN 0924-9338, https://doi.org/10.1016/S0924-9338(14)78345-2. (https://www.sciencedirect.com/science/article/pii/S0924933814783452)

[15] Gnanasegar R, Wolfman W, Galan LH, Cullimore A, Shea AK. Does menopause hormone therapy improve symptoms of depression? Findings from a specialized menopause clinic. Menopause. 2024 Apr 1;31(4):320-325. doi: 10.1097/GME.0000000000002325. Epub 2024 Feb 19. PMID: 38377443.

[16] Goldštajn MŠ, Mikuš M, Ferrari FA, Bosco M, Uccella S, Noventa M, Török P, Terzic S, Laganà AS, Garzon S. Effects of transdermal versus oral hormone replacement therapy in postmenopause: a systematic review. Arch Gynecol Obstet. 2023 Jun;307(6):1727-1745. doi: 10.1007/s00404-022-06647-5. Epub 2022 Jun 17. PMID: 35713694; PMCID: PMC10147786.

[17] Grainger, S. (n.d.). AMS Guide to MHT/HRT Doses Australia only - Australasian Menopause Society. https://www.menopause.org.au/hp/information-sheets/ams-guide-to-mht-hrt-doses

[18] Grainger, S. (n.d.-b). Treatment Options - Australasian Menopause Society. https://www.menopause.org.au/hp/management/treatment-options

[19] Samuthpongtorn C, Nguyen LH, Okereke OI, et al. Consumption of Ultraprocessed Food and Risk of Depression. JAMA Netw Open. 2023;6(9):e2334770. doi:10.1001/jamanetworkopen.2023.34770

Fezolinetant And Elizanetant: Learn the Facts About New Non-Hormonal Therapies For Menopause

By Susan Johnson
Reviewed by Rina Carlini, PhD
October 30, 2024

Image Source: Shutterstock ID: 635547857

For decades, hormone replacement therapy (HRT) has been the standard for treating menopausal symptoms, especially vasomotor symptoms (VMS) like hot flashes and night sweats, which affect nearly 80% of women during menopause.[1] However, HRT isn’t suitable for everyone. Women with a history of breast cancer and blood clots are not typically prescribed hormonal therapies since they can increase the risk of recurrence.

Until recently, there were only a few non-hormonal treatment options available for treating the disruptive symptoms of menopause, and they are mostly naturopathic treatments. However, that is changing with the development of new non-hormonal pharmaceutical drugs like fezolinetant (available under the commercial name VEOZAH™) and elinzanetant–the latest therapies and the first significant advances in more than two generations for managing vasomotor symptoms (VMS) associated with perimenopause and menopause.

What Is Fezolinetant And Elinzanetant?

Fezolinetant (developed by Astellas Pharma) and elinzanetant (developed by Bayer) are both non-hormonal oral medications that are indicated to specifically treat the VMS associated with menopause. In May 2023, fezolinetant made history as the first of its kind to be approved by the US Food and Drug Administration (FDA) for treating severe VMS.[2] Although Bayer’s elinzanetant hasn’t been commercialized yet, it was recently submitted for FDA approval in August 2024.[3]

How Do These Drugs Work?

Fezolinetant and elizanetant are not synthetic hormone drugs like conventional HRT drugs. Instead, these are a new class of drugs that act on the neural activity that causes flushing and sweating spells in women who are experiencing the perimenopause transition.

Recently, researchers identified a new pathway in the brain that could potentially be responsible for the VMS experienced by menopausal women. This pathway involves the kisspeptin/neurokinin B/dynorphin (KNDy) neurons, which contain neurokinin 3 (NK3) receptors on their surface. When estrogen binds to the NK3 receptors, it inhibits the KNDy neurons that cause VMS. On the other hand, neurokinin B (NKB) stimulates the receptors and signals the induction of hot flashes.[4]

Before menopause, a balance exists between estrogen and NKB in the body. This balance helps women regulate their body temperature based on their surroundings. However, during menopause, when estrogen levels drop significantly, the balance gets disrupted. More NKB binds to the NK3 receptors, causing increased KNDy neuronal activity, which in the long term leads to the hypertrophy (or enlargement) of KNDy neurons. This affects the woman’s ability to regulate core body temperature and triggers hot flashes. [4]

Fezolinetant is a selective NK3 receptor antagonist. It binds to NK3 receptors, making them unavailable for NKB to bind to, which in turn blocks neuronal activity and supports thermoregulation, thereby reducing the frequency and severity of menopausal VSM. [5]

Elizanetant works similar to fezolinetant. However, it is a dual receptor antagonist drug that targets two receptors in the brain: NK3, which regulates body temperature, and NK1, which affects mood and sleep. [6]

"Oftentimes, the focus on a lot of these drugs is hot flashes, hot flashes, hot flashes, but we know hot flashes do not occur in isolation,” said Chrisandra Shufelt, MD, professor and chair of general internal medicine and associate director of the Women's Health Research Center at Mayo Clinic. “Elinzanetant is an interesting compound because it actually works on sleep, and that was critical because sleep disturbance precedes many other menopausal symptoms,” she shared with Medscape Medical News

Who Should Consider Taking Non-Hormonal Therapies?

During the perimenopause transition phase, as a woman’s estrogen and progesterone levels start to drop significantly, menopausal hormone therapy (MHT) is considered one of the fastest and most effective ways to treat the bothersome VSM that can occur since MHT works to replenish the body’s estrogen and progesterone levels.

Some women should not be administered MHT even if they are requesting it to be prescribed by their doctors. Menopausal women with a history of breast or endometrial cancer, especially hormone receptor-positive (HR+) cancers, should not take MHT because these types of cancer cells have receptors for estrogen, progesterone, or both, which can significantly increase the risk that these tumors can grow, metastasize and cause more serious complications. For this reason, women who have had breast or endometrial cancer, any family members who had these cancers, or those women who are considered high risk for developing these cancers should not be prescribed MHT. [7]

In addition, women with a history of venous thromboembolic events or stroke, gallbladder problems, and coronary heart diseases should avoid MHT. However, they can instead consider non-hormonal treatments like fezolinetant or elinzanetant.

How Effective Are Non-Hormonal Therapies For Treating VMS?

SKYLIGHT 1

SKYLIGHT 1, a Phase III randomized controlled clinical study, was performed to assess the effectiveness of fezolinetant in treating moderate-to-severe vasomotor symptoms associated with menopause. The clinical study included over 500 women between 40 and 65 years of age, who were selected from around the world and who had experienced at least seven hot flashes a day. [8]

The study participants were split into three groups, one receiving a placebo intervention and the other two receiving 35 mg and 45 mg of fezolinetant, respectively. After 4 weeks, the women who were administered fezolinetant reported a reduction in the frequency and severity of hot flashes. After 12 weeks, 45% of women taking 30 mg of fezolinetant, 57% of women taking 45 mg of fezolinetant, and 30% of the placebo group reported a reduction in the frequency of hot flashes. [8]

The study's authors also wrote that the participants reported better quality of life and fewer night-time awakenings. [8]

OASIS 1 and 2

Bayer conducted three Phase III clinical studies–OASIS 1, 2, and 3–to analyze the effectiveness of elinzanetant. OASIS 1 and 2 were specifically conducted to analyze the impact of elinzanetant on moderate to severe VMS, its effects on sleep disturbances, and overall menopause-related quality of life. These trials followed a double-blind, placebo-controlled design to ensure accurate results.

Both OASIS 1 and 2 studies met all primary endpoints. Compared to the placebo, there was a 50% reduction in the frequency and severity of hot flashes in 80% of participants taking elinzanetant by the fourth and twelfth weeks. In addition, the participants also said they slept better while taking elinzanetant. Improvement in these areas was seen as early as week one, indicating a rapid onset of action. The drug’s safety was consistent with prior studies, with no unexpected adverse effects.

According to Dr. Michelle Jacobson, a Canadian OB/GYN physician and certified menopause specialist based in Toronto, Canada, these findings mark a significant milestone for managing menopausal symptoms. She said, “As a menopause specialist, I am truly excited to see the results of the Phase III trials on elinzanetant. For so long, we have been treating those suffering from menopausal symptoms with second-line, non-indicated therapies. Now, we are one step closer to having effective, indicated, and safe treatments for our patients. I look forward to being able to offer women a novel treatment that has such positive outcomes once it is approved by Health Canada. The more options we have, the better we can individualize therapies for our patients to help them live their best and healthiest lives possible."

Claudio N Soares, MD, PhD, who is a Professor of Psychiatry at Queen’s University in Canada, an experienced clinical researcher in menopause and women’s mental health, and President-elect of The Menopause Society, also expressed similar views.

“These results are really encouraging. For too long, we have underestimated, sometimes even overlooked, the negative impact that menopausal symptoms–hot flashes, sleep disturbances, mood changes–may have on a woman’s health and quality of life. It is reassuring to see that this is no longer the case and that women may soon have access to novel, non-hormonal options to alleviate these symptoms and improve their quality of life”.

While the findings of OASIS 3 have not yet been published, the study was performed with a large sample size of participants to confirm the findings of OASIS 1 and 2. [9][10]

Are There Any Side Effects?

In the SKYLIGHT 1 study, a significant number of participants had experienced side effects or adverse reactions (listed below), which were 37% of women taking 30 mg and 43% of women taking 45 mg Fezolinetant. Interestingly, 45% of women in the placebo group (who were not taking any drug) also reported similar side effects. So, the difference in side effects between the drug medication group and placebo groups was minimal. [8]

The most commonly reported side effects included:

Headache
Abdominal pain
Diarrhea
Insomnia
Back pain
Elevated hepatic transaminase levels (potential risk of liver damage)

The study also included a warning for potential liver damage or elevated hepatic transaminase levels. Therefore, women considering Fezolinetant are advised to have their baseline bloodwork done to evaluate liver function and injury before starting the medication. While on the drug, follow-up blood tests should be performed every three months for the first nine months of treatment to monitor liver health.

Additionally, patients should watch for symptoms and signs of liver damage, such as nausea, vomiting, or jaundice (yellowing of the skin and eyes), and contact their physician if these signs appear.

With elinzanetant, no participant showed signs of hepatotoxicity or possible drug-induced liver injury. Safety assessments were performed to look for adverse effects in participants and included endometrial biopsies, bone mineral density, weight, and blood tests. It was found that 30.4% of participants taking elinzanetant and 14.6% of participants taking the placebo pill reported adverse effects, which were, most commonly, headache, fatigue, and sleepiness. [9]

Conclusions

Over 75% of menopausal women experience VMS, with 25% describing their symptoms as severe. In one-third of women, these symptoms can persist for seven years or more.[11] A pooled analysis of individual-level data revealed that women experiencing both persistent and severe hot flashes and night sweats had a significantly higher risk of cardiovascular disease (CVD). [12] In such cases, having access to medications like fezolinetant and elinzanetant will not only expand treatment options for women but also prove to be an effective alternative for women who should not take HRT.

It should be noted that both fezolinentant and elinzanetant are very new classes of drugs that do not have a long clinical history, and as such, the clinical practice guidelines on how to incorporate them into the treatment regimen are currently unclear. While both these drugs will prove to be exciting options for women, whether they can be used in combination with other treatments for menopausal symptoms still needs further study.

References:

[1] Gold EB, Colvin A, Avis N, Bromberger J, Greendale GA, Powell L, Sternfeld B, Matthews K. Longitudinal analysis of the association between vasomotor symptoms and race/ethnicity across the menopausal transition: study of women's health across the nation. Am J Public Health. 2006 Jul;96(7):1226-35. doi: 10.2105/AJPH.2005.066936. Epub 2006 May 30. PMID: 16735636; PMCID: PMC1483882.

[2] https://www.fda.gov/news-events/press-announcements/fda-approves-novel-drug-treat-moderate-severe-hot-flashes-caused-menopause

[3] https://www.bayer.com/en/us/news-stories/new-drug-application-to-us-fda-for-elinzanetant

[4] Prague JK, Roberts RE, Comninos AN, Clarke S, Jayasena CN, Mohideen P, Lin VH, Stern TP, Panay N, Hunter MS, Webber LC, Dhillo WS. Neurokinin 3 receptor antagonism rapidly improves vasomotor symptoms with sustained duration of action. Menopause. 2018 Aug;25(8):862-869. doi: 10.1097/GME.0000000000001090. PMID: 29533369; PMCID: PMC6092106.

[5] Santoro N, Waldbaum A, Lederman S, Kroll R, Fraser GL, Lademacher C, Skillern L, Young J, Ramael S. Effect of the neurokinin 3 receptor antagonist fezolinetant on patient-reported outcomes in postmenopausal women with vasomotor symptoms: results of a randomized, placebo-controlled, double-blind, dose-ranging study (VESTA). Menopause. 2020 Dec;27(12):1350-1356. doi: 10.1097/GME.0000000000001621. PMID: 32769757; PMCID: PMC7709922.

[6] Pawsey S, Mills EG, Ballantyne E, Donaldson K, Kerr M, Trower M, Dhillo WS. Elinzanetant (NT-814), a Neurokinin 1,3 Receptor Antagonist, Reduces Estradiol and Progesterone in Healthy Women. J Clin Endocrinol Metab. 2021 Jul 13;106(8):e3221-e3234. doi: 10.1210/clinem/dgab108. PMID: 33624806; PMCID: PMC8277204.

[7] Clusan L, Ferrière F, Flouriot G, Pakdel F. A Basic Review on Estrogen Receptor Signaling Pathways in Breast Cancer. Int J Mol Sci. 2023 Apr 6;24(7):6834. doi: 10.3390/ijms24076834. PMID: 37047814; PMCID: PMC10095386.

[8] Lederman S, Ottery FD, Cano A, Santoro N, Shapiro M, Stute P, Thurston RC, English M, Franklin C, Lee M, Neal-Perry G. Fezolinetant for treatment of moderate-to-severe vasomotor symptoms associated with menopause (SKYLIGHT 1): a phase 3 randomized controlled study. Lancet. 2023 Apr 1;401(10382):1091-1102. doi: 10.1016/S0140-6736(23)00085-5. Epub 2023 Mar 13. PMID: 36924778.

[9] Pinkerton JV, Simon JA, Joffe H, et al. Elinzanetant for the Treatment of Vasomotor Symptoms Associated With Menopause: OASIS 1 and 2 Randomized Clinical Trials. JAMA. 2024;332(16):1343–1354. doi:10.1001/jama.2024.14618

[10] https://www.bayer.com/en/ca/bayers-elinzanetant-meets-all-primary-and-key-secondary-endpoints-in-oasis-1-and-2-phase-iii

[11] https://thebms.org.uk/2023/12/new-treatment-for-vasomotor-symptoms-hot-flushes-and-night-sweats-licensed-by-the-mhra/

[12] Zhu, Dongshan et al.Vasomotor menopausal symptoms and risk of cardiovascular disease: a pooled analysis of six prospective studies; American Journal of Obstetrics & Gynecology, Volume 223, Issue 6, 898.e1 - 898.e16

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Testosterone as a Supplemental Form of Menopausal Hormone Therapy (MHT): The Facts You Should Know

By Susan Johnson
Reviewed by Rina Carlini, PhD
October 16, 2024

Image Source: Shutterstock ID 1114736909

Menopause is a natural phase in a woman’s life that comes with a host of uncomfortable symptoms, which can be classified broadly into four main categories: 1) Genitourinary Syndrome (GSM), 2) Vasomotor symptoms and related heart health issues, 3) musculoskeletal issues, and 4) Cognitive issues. Of these, GSM typically presents itself with low libido, dyspareunia (painful intercourse), vaginal atrophy, frequent urination and sometimes incontinence. This can lead to poor quality of life and social stress for your relationships.

There has been much discourse about testosterone being a worthwhile supplement for managing GSM (the genitourinary symptoms of menopause), and there’s a growing number of women who are demanding it from their OB/GYN physicians as a part of their Menopausal Hormone Therapy (MHT). However, testosterone supplementation isn’t a solution that’s safe or suitable for all women.

Testosterone And Menopause

Testosterone is commonly believed to be a male hormone. However, women also make this hormone, but in lower amounts than men.

The ovaries and the adrenal glands (located on top of the kidneys) produce testosterone, which plays a vital role in libido, bone strength, sexual response, cognitive performance, energy levels, and more.

Though women produce three to four times as much testosterone as estrogen before menopause [1], their testosterone levels gradually decrease as they age. During menopause, the testosterone levels in most women fall to about one-quarter of what they were at their peak during their 20s. [2] A sudden decrease in testosterone levels also happens when both the ovaries are removed. [3]

When the hormone levels fall, women start experiencing depression, lower energy, and lower sex drive (libido).

How Does Testosterone Help Treat The GSM Symptoms?

Testosterone is best known for improving libido. However, testosterone receptors are present all over the body, so its effects are far-reaching.

The hormone plays a vital role in strengthening nerves and arteries in the brain, thereby contributing to mental sharpness and clarity and protecting against memory loss. It also stimulates the release of serotonin and dopamine, improving overall mood and feelings of pleasure. It further boosts overall energy levels by improving muscle mass and bone strength. [4]

Perhaps this is why a lot of women take testosterone as part of their hormone replacement therapy (HRT), reporting: [5]

Increased libido
Improved energy
Enhanced muscle strength
Improved focus and mental clarity
Improved sleep

Who Should Use Testosterone, And Who Shouldn’t?

Due to the lack of long-term safety data for cardiovascular and breast outcomes, testosterone isn’t licensed for use in women, except in Australia, where Androfeme (1% of testosterone cream) is approved. [6]

However, specialist doctors do prescribe testosterone supplementations to women whose sex drive doesn’t improve with MHT. This is because the NICE Menopause Guideline (NG23) [7] and the British Menopause Society (BMS) [8] state that a trial of HRT should be given to women before considering testosterone supplementation.

Testosterone can be taken as a tablet/capsule. However, it isn’t recommended due to its negative impact on blood cholesterol levels. Transdermal delivery, such as gel, cream, patches, or implants, is generally considered the safest in doses that reflect young women’s testosterone levels.

Side Effects

Adverse effects of testosterone in women are uncommon, given the supplementations are provided within the physiological range. The most common side effects include:

Hair growth
Acne
Weight gain

These effects are reversible and can be addressed either by discontinuing the use of testosterone or by lowering its dosage. More severe but rare side effects include:

Alopecia
Deepening of voice
Clitoral enlargement

Typically, testosterone has to be prescribed for 3-6 months before its efficacy can be thoroughly evaluated. [9] Furthermore, an annual re-evaluation of ongoing usage is performed just like with the standard HRT to weigh the pros and cons of long-term usage.

Women with an active liver or cardiovascular disease or with a history of hormone-sensitive breast or endometrial cancer should avoid testosterone usage. [10]

References:

[1] Scott A, Newson L. Should we be prescribing testosterone to perimenopausal and menopausal women? A guide to prescribing testosterone for women in primary care. Br J Gen Pract. 2020 Mar 26;70(693):203-204. doi: 10.3399/bjgp20X709265. PMID: 32217602; PMCID: PMC7098532.

[2] Skiba MA, Bell RJ, Islam RM, Handelsman DJ, Desai R, Davis SR. Androgens During the Reproductive Years: What Is Normal for Women? J Clin Endocrinol Metab. 2019 Nov 1;104(11):5382-5392. doi: 10.1210/jc.2019-01357. PMID: 31390028.

[3] Rocca WA, Shuster LT, Grossardt BR, Maraganore DM, Gostout BS, Geda YE, Melton LJ 3rd. Long-term effects of bilateral oophorectomy on brain aging: unanswered questions from the Mayo Clinic Cohort Study of Oophorectomy and Aging. Womens Health (Lond). 2009 Jan;5(1):39-48. doi: 10.2217/17455057.5.1.39. PMID: 19102639; PMCID: PMC2716666.

[4] Bassil N, Alkaade S, Morley JE. The benefits and risks of testosterone replacement therapy: a review. Ther Clin Risk Manag. 2009 Jun;5(3):427-48. doi: 10.2147/tcrm.s3025. Epub 2009 Jun 22. PMID: 19707253; PMCID: PMC2701485.

[5] Glynne S, Kamal A, Kamel AM, Reisel D, Newson L. Effect of transdermal testosterone therapy on mood and cognitive symptoms in peri- and postmenopausal women: a pilot study. Arch Womens Ment Health. 2024 Sep 16. doi: 10.1007/s00737-024-01513-6. Epub ahead of print. PMID: 39283522.

[6] https://www.nps.org.au/assets/medicines/47d5a936-d106-46a4-9278-a53300ff76e5-reduced.pdf

[7] https://www.nice.org.uk/guidance/ng23

[8] https://thebms.org.uk/wp-content/uploads/2023/10/02-BMS-ConsensusStatement-BMS-WHC-2020-Recommendations-on-HRT-in-menopausal-women-SEPT2023-A.pdf

[9] https://thebms.org.uk/wp-content/uploads/2022/12/08-BMS-TfC-Testosterone-replacement-in-menopause-DEC2022-A.pdf

[10] Davis SR. Cardiovascular and cancer safety of testosterone in women. Curr Opin Endocrinol Diabetes Obes. 2011 Jun;18(3):198-203. doi: 10.1097/MED.0b013e328344f449. PMID: 21415740.

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What are Uterine Fibroids?

By Henry Xu PhD., Joanne Tejeda, PhD.
July 12, 2024

Uterine fibroids, also known as leiomyomas or myomas, are non-cancerous growths in the uterus composed of muscle and fibrous tissue. They can range in size from a pea to as large as a melon.

Globally, there are 226 million cases of uterine fibroids, with the highest prevalence among women aged 40-50. About 80% of women will develop uterine fibroids in their lifetime.

In the United States, about 26 million women aged 15 to 50 that are diagnosed with fibroids [1]. By age 50, nearly 80% of Black women and 70% of white women will develop fibroids. While experiences vary, about 25% of women with fibroids suffer from severe symptoms requiring treatment [2].

What Causes Uterine Fibroids?

The exact cause of uterine fibroids is not fully understood, but several factors are believed to contribute to their development, these include [3]:

1. Hormones that regulate the menstrual cycle, estrogen and progesterone, promote the growth of fibroids. When hormone levels drop after menopause, fibroid growth tends to decrease [4].

2. Evidence suggests that family genetics is a contributing factor as uterine fibroids tend to occur within the family [5].

3. Race is a key factor for uterine fibroids, as African-American women are 3-times more likely to develop fibroids and at a younger age compared to women of other racial groups [6].

4. Obesity has been linked to an increase in the risk of fibroids [7].

5. Vitamin D deficiency is also associated with increased risk of uterine fibroids [8].

6. Women with high blood pressure typically have a significantly higher risk of developing uterine fibroids [5].

Symptoms of Uterine Fibroids [2]:

Heavy menstrual bleeding

Prolonged periods (lasting more than a week)

Iron Deficiency Anemia

Pelvic pain or pressure

Frequent urination

Difficulty emptying the bladder

Constipation

Backache

Leg pains

Reproductive issues, such as infertility or pregnancy complications

Diagnosis of Uterine Fibroids:

Diagnosis typically begins with taking the patient’s history and identifying symptoms related to uterine fibroids. A pelvic exam is then conducted to check for irregularities in the shape and size of the uterus. In certain cases, blood tests may be conducted to rule out other causes of symptoms, like anemia from heavy bleeding.

Imaging tests are crucial for an accurate diagnosis. Ultrasound is the primary imaging technique used due to its ability to visualize fibroids and assess their size, number, and location. Saline infusion, involving the injection of a salt solution into the uterus, is often used to create clearer ultrasound images [9].

Magnetic resonance imaging (MRI) is another valuable tool, especially for detailed mapping of fibroids, which is essential for treatment planning. MRI also helps distinguish fibroids from other pelvic conditions. Other traditional imaging techniques include hysteroscopy, which allows direct visualization of the uterine cavity using a thin, lighted scope, aiding in the identification of fibroids. [10].

Treatments of Uterine Fibroids:

Medications

For mild symptoms, over-the-counter pain relief can be used. Hormonal treatments, such as oral contraceptives or special injections that lower hormone levels, can also help shrink fibroids [4].

Non-Invasive Procedures

Radiofrequency ablation is a procedure that uses radio energy and heat to remove uterine fibroids. It is performed with a small, energized probe that is passed through the vagina and cervix into the uterus, guided by ultrasound throughout the procedure [11].

Minimally Invasive Procedures

Uterine artery embolization (UAE) is a treatment in which surgeons inject small particles into the arteries surrounding the fibroid to cut off its blood flow, causing it to shrink [12].

Radiofrequency ablation can also be used in minimally invasive procedures, where laparoscopic scopes are inserted into small incisions to guide the procedure [13].

Traditional Surgical Procedures

An abdominal myomectomy involves making an incision in the abdominal wall to access the uterus and surgically remove fibroids from its surface.

For women with severe symptoms who do not plan on having more children in the future, hysterectomy is used as a last resort [14].

Treatment of uterine fibroids can be time-consuming. Many women often go through multiple doctor visits before being diagnosed, and up to 32% of diagnosed women wait more than 5 years before seeking treatment [2]. Improved access to educational resources is needed to help guide women in their journey when seeking treatment for uterine fibroids.

New Medical Innovations

Medical device innovators are constantly developing new treatment tools for the non-invasive removal of uterine fibroids. Radiologist Dr. Elizabeth David at Sunnybrook Health Sciences Centre in Toronto is working on shrinking fibroids using high-intensity focused ultrasound guided by MRI. She recently completed a clinical trial in which 90% of patients reported being symptom-free after the procedure. [15].

Helpful Resources:

Living with fibroids can be challenging, with women reporting an average loss of 5.1 work hours per week due to the condition [1].

The Uterine Fibroids Toolkit: A Patient Empowerment Guide by the Society for Women's Health Research is a fantastic resource, offering information to help you understand your condition and make informed decisions.

Join the Healthyher.Life community to connect with others who have had similar experiences with fibroids.

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References:

[1] Lou, Zheng et al. “Global, regional, and national time trends in incidence, prevalence, years lived with disability for uterine fibroids, 1990-2019: an age-period-cohort analysis for the global burden of disease 2019 study.” BMC public health vol. 23,1 916. 19 May. 2023, doi:10.1186/s12889-023-15765-x

[2] Society for Women's Health Research. *Uterine Fibroids Toolkit: A Patient Empowerment Guide*. Society for Women's Health Research, 2023.

[3] Stewart, E A. “Uterine fibroids.” Lancet (London, England) vol. 357,9252 (2001): 293-8. doi:10.1016/S0140-6736(00)03622-9

[4] Bulun, Serdar E. “Uterine fibroids.” The New England journal of medicine vol. 369,14 (2013): 1344-55. doi:10.1056/NEJMra1209993

[4] American College of Obstetricians and Gynecologists. “Management of Symptomatic Uterine Leiomyomas.” ACOG Practice Bulletin No. 228, July 2021.

[5] Stewart, E A et al. “Epidemiology of uterine fibroids: a systematic review.” BJOG : an international journal of obstetrics and gynaecology vol. 124,10 (2017): 1501-1512. doi:10.1111/1471-0528.14640

[6] Eltoukhi, Heba M et al. “The health disparities of uterine fibroid tumors for African American women: a public health issue.” American journal of obstetrics and gynecology vol. 210,3 (2014): 194-9. doi:10.1016/j.ajog.2013.08.008

[7] Pavone, Dora et al. “Epidemiology and Risk Factors of Uterine Fibroids.” Best practice & research. Clinical obstetrics & gynaecology vol. 46 (2018): 3-11. doi:10.1016/j.bpobgyn.2017.09.004

[8] Baird, Donna Day et al. “Vitamin d and the risk of uterine fibroids.” Epidemiology (Cambridge, Mass.) vol. 24,3 (2013): 447-53. doi:10.1097/EDE.0b013e31828acca0

[9] Palheta, Michel Santos et al. “Reporting of uterine fibroids on ultrasound examinations: an illustrated report template focused on surgical planning.” Radiologia brasileira vol. 56,2 (2023): 86-94. doi:10.1590/0100-3984.2022.0048

[10] De La Cruz, Maria Syl D, and Edward M Buchanan. “Uterine Fibroids: Diagnosis and Treatment.” American family physician vol. 95,2 (2017): 100-107.

[11] Christoffel, Ladina et al. “Transcervical Radiofrequency Ablation of Uterine Fibroids Global Registry (SAGE): Study Protocol and Preliminary Results.” Medical devices (Auckland, N.Z.) vol. 14 77-84. 3 Mar. 2021, doi:10.2147/MDER.S301166

[12] Gupta, Janesh K et al. “Uterine artery embolization for symptomatic uterine fibroids.” The Cochrane database of systematic reviews ,5 CD005073. 16 May. 2012, doi:10.1002/14651858.CD005073.pub3

[13] Milic, Andrea et al. “Laparoscopic ultrasound-guided radiofrequency ablation of uterine fibroids.” Cardiovascular and interventional radiology vol. 29,4 (2006): 694-8. doi:10.1007/s00270-005-0045-9

[14] Guarnaccia, M M, and M S Rein. “Traditional surgical approaches to uterine fibroids: abdominal myomectomy and hysterectomy.” Clinical obstetrics and gynecology vol. 44,2 (2001): 385-400. doi:10.1097/00003081-200106000-00024

[15] Single Arm Study Using the Symphony -- MRI Guided Focused Ultrasound System for the Treatment of Leiomyomas (HIFUSB). ClinicalTrials.gov identifier: NCT03323905. Updated July 9, 2024. Accessed July11, 2024 https://clinicaltrials.gov/study/NCT03323905

The Silent Burden: Iron Deficiency and Anemia in Women

By Henry Xu, Ph.D
Reviewed by Joanne Tejeda, PhD and Rina Carlini, PhD
original post: July 2, 2024 | updated: Sept 16, 2024

Iron is an essential mineral for your body, playing crucial roles in your immune and cardiovascular systems. It is mainly used to produce a protein called hemoglobin, which carries oxygen in red blood cells. When your body lacks sufficient iron, it can result in iron deficiency anemia, a common health issue affecting many women worldwide. Globally, more than 33% of women aged 15-49 suffer from anemia, with over 800 million cases due to iron deficiency – twice as many compared to men [1]. In Canada, an estimated 29% of women aged 19-50 experience iron deficiency anemia. [2]. These conditions can lead to various health complications, impacting overall quality of life and productivity.

In this article, we explore how to identify iron deficiency anemia and manage iron levels. Catching symptoms of anemia early and taking steps to maintain healthy iron levels are crucial for women's health.

What Causes Iron Deficiency Anemia in Women?

Iron deficiency is a condition where the body does not have enough iron to produce hemoglobin. When this condition worsens and there isn’t enough oxygen in red blood cells, it can result in iron deficiency anemia, potentially leading to tissue and organ damage. [3]. Several factors contribute to the increased prevalence of iron deficiency in women. Women of reproductive age are particularly susceptible to iron deficiency due to blood loss during menstruation [4].

Abnormal uterine bleeding (AUB) – where bleeding from the uterus is abnormal – affects up to 25% of women of reproductive age. The most common subtype of AUB is heavy menstrual bleeding (menorrhagia), which significantly increases iron loss [5]. An ongoing comprehensive review by Dr. Michelle Zeller from McMaster University is examining the effectiveness of iron treatments for AUB [6]. This research aims to improve our understanding of how iron treatments can enhance health outcomes for women with iron deficiency due to AUB.

Iron deficiency is also a common issue for expecting and postpartum mothers. The increased iron demands during pregnancy and lactation can lead to the rapid depletion of iron stores in the mother’s body, especially if the pregnancy is not supported with additional iron through nutrients or supplements.

An unbalanced diet with limited consumption of iron-rich foods, such as red meat, poultry, and fish, is another common factor leading to iron deficiency. Vegetarian and vegan diets may also pose a risk if not carefully managed to include alternative iron sources. In addition, several gastrointestinal conditions, such as celiac disease, Crohn's disease, inflammatory bowel disease (IBS), and those who have undergone gastric bypass surgery, can decrease iron absorption, leading to iron deficiency.

Common Symptoms of Iron Deficiency Anemia

The symptoms of iron deficiency and iron deficiency anemia can vary in severity and may include [4, 7]:

Iron Deficiency symptoms (1080x1080) (1).png

The Impact of Iron Deficiency Anemia on Women’s Health

Adolescent Women

During these developmental years, bodies are rapidly changing and growing, making iron even more important. Without enough iron, adolescents can feel tired, weak, and have trouble concentrating, impacting their performance and daily activities. Additionally, as girls begin menstruating, they lose iron each month, increasing their risk of deficiency. Ensuring sufficient iron is essential for maintaining their energy levels, supporting growth, and promoting overall well-being [8].

Adult Women

Iron is equally important for adult women. Without healthy levels of iron, they might feel tired, weak, or even dizzy, greatly impacting their work and social life. Women periodically lose iron during menstruation, making it even harder to meet the body’s iron needs. Heavy and prolonged athletic activities also increase iron loss through sweating [4].

Pregnant Women

Iron needs increase significantly to support fetal development and increased blood volume. Pregnant women are often advised to take prenatal vitamins that include iron to prevent deficiency. Monitoring iron levels throughout pregnancy is essential to ensure both maternal and fetal health. Iron-deficient mothers can encounter complications during pregnancy, including preterm delivery and low birth weight [4].

Perimenopausal Women

During perimenopause, women may experience irregular or increased menstrual volume. These changes can contribute to increased iron loss and result in iron deficiency anemia. Some symptoms of perimenopause, such as fatigue and headaches, might overlap with iron deficiency symptoms, making it important for perimenopausal women to regularly check their blood iron levels to avoid developing anemia [4].

Postmenopausal Women

Postmenopausal women generally have a lower risk of iron deficiency due to the cessation of menstrual blood loss. However, they can still be affected by insufficient dietary iron or gastrointestinal issues. Regular health check-ups and maintaining a balanced diet are important for preventing iron deficiency in this age group [4].

How is Iron Deficiency Anemia Diagnosed?

Diagnosing iron deficiency anemia involves a combination of clinical evaluation and laboratory tests [3], including:

1. A Complete Blood Count (CBC), which is a comprehensive blood test used to evaluate overall health and detect a variety of disorders, including anemia, infection, and many other diseases. The CBC measures several components and features of your blood, such as Red Blood Cells (RBCs), White Blood Cells (WBC), Hemoglobin (Hgb), Hematocrit (Hct), and Platelets.

2. A Serum Ferritin Test that measures the level of ferritin in your blood. Ferritin is a protein that stores iron in your body's cells, and the amount of ferritin in your blood reflects the amount of stored iron. This test helps to evaluate your body's iron levels and diagnose conditions related to iron deficiency or excess. Low ferritin levels indicate low iron stores, which can lead to iron deficiency anemia.

Interpretation of Serum Ferritin Test Results

Table adapted from NIH National Heart, Lung, and Blood Institute [9, 10]

3. A Serum Iron and Total Iron-Binding Capacity (TIBC) test that measures the amount of circulating iron and the blood’s capacity to bind iron, respectively. Low serum iron and high TIBC levels are indicative of iron deficiency.

4. The Transferrin Saturation Test used to evaluate how much iron is bound to transferrin, the protein that transports iron in the blood. Low transferrin saturation indicates insufficient iron supply.

Treatment and Prevention

The primary goals in treating iron deficiency anemia are to replenish iron stores and address any underlying causes [3,4]. Dietary changes are usually a fundamental step in treatment and prevention. Heme iron, found in animal products, is more readily absorbed by the body compared to non-heme iron in plant-based foods. Including vitamin C-rich foods in meals can enhance non-heme iron absorption.

For women with dietary restrictions or needing additional iron, ferrous sulfate and other oral supplements are commonly used to treat iron deficiency. While effective, these supplements can cause gastrointestinal side effects like constipation and nausea, which can be mitigated by taking them with meals and consuming fiber. For those who cannot tolerate oral iron or have severe deficiencies, intravenous iron infusions may be necessary, especially in cases of absorption issues. Always consult your doctor to determine which supplement option is best for you.

If you're persistently tired or noticing other symptoms, consult a healthcare professional about iron deficiency anemia. Proactive steps like eating a balanced diet and getting regular check-ups can help maintain healthy iron levels and ensure your well-being.

New Update: September 2024 Iron Deficiency Revised Guidelines for Ontario

New guidelines introduced in Ontario on September 9, 2024, have raised the thresholds for diagnosing iron deficiency, allowing for earlier detection and improved treatment. Previously, ferritin levels below 10 to 15 micrograms per litre were flagged as abnormal, but many patients with symptoms of iron deficiency went undiagnosed due to these low thresholds. The updated standards now raise the baseline to 30 micrograms per litre for adults and 20 for children, aligning with global research and evidence dating back to 1992. This change is expected to significantly improve patient care, especially for women, marginalized communities, and those at higher risk due to conditions like heavy menstrual bleeding.

Below is the updated table reflecting the new serum ferritin level thresholds:

Interpretation of Serum Ferritin Test Results ( Per New Ontario Guidelines)

These guidelines are a major step forward in addressing health equity and improving outcomes for those who have long suffered from undiagnosed iron deficiency.

Don’t Miss Out – Access the Video Recording Now!

On July 24th, 2024, Healthyher.Life had the privilege of hosting Dr. Michelle Zeller, a clinical hematologist and Associate Professor at McMaster University, for an insightful Women Talking™ Wednesday event: "Iron is Essential for Your Health and Vitality – Are You Getting Enough?"

If you’re wondering whether you have unmet iron needs or how iron plays a critical role in your health, this is your chance to get informed. Dr. Zeller’s expert insights on the importance of iron and how to ensure you’re getting enough could make a real difference in your well-being.

Access Video Recording

References:

[1] GBD 2021 Anaemia Collaborators. “Prevalence, years lived with disability, and trends in anaemia burden by severity and cause, 1990-2021: findings from the Global Burden of Disease Study 2021.” The Lancet. Haematology vol. 10,9 (2023): e713-e734. doi:10.1016/S2352-3026(23)00160-6

[2] Cooper, M., Bertinato, J., Ennis, J. K., Sadeghpour, A., Weiler, H. A., Dorais, V.. “Population Iron Status in Canada: Results from the Canadian Health Measures Survey 2012-2019.” The Journal of Nutrition, Mar 2023, Volume 153:5, pp1534-1543. doi:10.1016/j.tjnut.2023.03.012

[3] Kumar, A., Sharma, E., Marley, A., Samaan, M. A., & Brookes, M. J., “Iron deficiency anaemia: pathophysiology, assessment, practical management.” BMJ open gastroenterology, 2022, Volume 9:1:e00759, doi: 10.1136/bmjgast-2021-000759

[4] Percy, L., Mansour, D., Fraser, I. “Iron deficiency and iron deficiency anaemia in women.” Best Practice & Research Clinical Obstetrics & Gynaecology, 2017, Volume 40, pp 55-67, doi: 10.1016/j.bpobgyn.2016.09.007

[5] Whitaker, Lucy, and Hilary O D Critchley. “Abnormal uterine bleeding.” Best practice & research. Clinical obstetrics & gynaecology vol. 34 (2016): 54-65. doi:10.1016/j.bpobgyn.2015.11.012

[6] Nazaryan, H., Watson, M., Ellingham, D., Thakar, S., Wang, A., Pai, M., Liu, Y., Rochwerg, B., Gabarin, N., Arnold, D., Sirotich, E., Zeller, M. P. “Impact of iron supplementation on patient outcomes for women with abnormal uterine bleeding: a protocol for a systematic review and meta-analysis.” Systematic reviews, Jul 2023, Volume 12:1, pp 121, doi: 10.1186/s13643-023-02222-4

[7] “Iron-Deficiency Anemia.” Office on Women's Health, U.S. Department of Health and Human Services, Feb. 2022, www.womenshealth.gov/a-z-topics/iron-deficiency-anemia.

[8] Aksu, Tekin, and Şule Ünal. “Iron Deficiency Anemia in Infancy, Childhood, and Adolescence.” Turkish archives of pediatrics vol. 58,4 (2023): 358-362. doi:10.5152/TurkArchPediatr.2023.23049

[9] “Iron-Deficiency Anemia.” National Heart Lung and Blood Institute, U.S. Department of Health and Human Services, 24 Mar. 2022, www.nhlbi.nih.gov/health/anemia/iron-deficiency-anemia.

[10] Mei, Zuguo et al. “Physiologically based serum ferritin thresholds for iron deficiency in children and non-pregnant women: a US National Health and Nutrition Examination Surveys (NHANES) serial cross-sectional study.” The Lancet. Haematology vol. 8,8 (2021): e572-e582. doi:10.1016/S2352-3026(21)00168-X

[11] Harrison, L. (2024, September 9). Ontario's new iron deficiency guidelines may change lives: Doctors. CBC News. www.cbc.ca/news/canada/toronto/iron-deficiency-bloodwork-testing-ontario-1.7314795

Association of cortisol in women with biomarkers of Alzheimer’s risk

Reviewed by Rina Carlini, PhD
April 22, 2024

Image licensed from Shutterstock #2188096049

New research insights about menopausal women’s brain health was reported in March 2024 in a neuroscience research study led by Dr. Lisa Mosconi and co-workers of the Weill Cornell Medicine in New York City [1]. The research investigated the sex-specific relationship between serum cortisol levels and brain biomarkers associated with Alzheimer's disease risk.

Alzheimer's disease is a progressive neurodegenerative disorder characterized by cognitive decline and memory loss, with increasing evidence suggesting a link between stress-related hormones such as cortisol and the development of Alzheimer's Disease (AD). However, existing research has largely overlooked potential sex differences in these associations.

To address this gap, Dr. Mosconi and colleagues conducted a study involving 277 participants, to examine the relationship between serum cortisol levels and brain biomarkers of Alzheimer's risk, while considering sex-specific differences. The study included both male and female participants aged 35–65 years who have risk factors for late-onset AD such as a family history and/or the APOE4 genotype, and who were assessed prior to the study of having normal cognitive function. The research methods used advanced neuroimaging techniques to assess various brain biomarkers associated with Alzheimer's disease, such as amyloid-beta deposits and neurodegeneration.

The study revealed sex-specific associations between serum cortisol levels and brain biomarkers of Alzheimer's risk. Specifically, higher levels of serum cortisol were associated with increased amyloid-beta deposits in women but not in men. Amyloid-beta deposition is a hallmark pathological feature of Alzheimer's disease and is believed to contribute to the development and progression of the condition. The research findings suggests that elevated cortisol levels may exacerbate amyloid-beta deposition in women, thereby increasing their risk of developing Alzheimer's disease.

Furthermore, the study found no significant association between serum cortisol levels and neurodegeneration biomarkers in either men or women. Neurodegeneration is another critical aspect of Alzheimer's pathology, and is characterized by the progressive loss of neurons and brain tissue. The lack of association suggests that cortisol may have a more specific effect on amyloid-beta deposition rather than overall neurodegeneration, in the context of Alzheimer's disease risk.

The researchers did not observe reduced cognitive performance in women compared to men, nor did their study confirm the findings of a previous research study in 2018 that reported a stronger association of cortisol with memory in women compared to age-controlled men [2]. It was recommended that to advance this research, a broad range of cognitive tests might be needed to capture the subtle cognitive changes in men and women that are associated with cortisol levels.

In summary, Dr. Mosconi's study sheds light on the sex-specific associations of serum cortisol with brain biomarkers of Alzheimer's risk. The findings underscore the importance of considering sex differences in Alzheimer's research and highlight the potential role of stress-related hormones in the development and progression of the disease. Further research in this area may contribute to the development of personalized strategies and therapeutic interventions for Alzheimer's prevention and treatment.

References

Mosconi, L., Williams, S., Carlton, C. et al. Sex-specific associations of serum cortisol with brain biomarkers of Alzheimer’s risk. Scientific Reports, volume 14, 5519 (2024). https://doi.org/10.1038/s41598-024-56071-9
Echouffo-Tcheugui, J. B. et al. Circulating cortisol and cognitive and structural brain measures: The Framingham Heart Study. Neurology 91, e1961–e1970 (2018). https://doi.org/10.1212/WNL.0000000000006549

Stress, age, BMI and gastrointestinal factors are associated with severity of menopause symptoms

Reviewed by Rina Carlini, PhD
October 13, 2023

A group of physician researchers from Vilnius University in Lithuania examined whether there was any connection between the gut microbiome and menopause symptoms in women. They launched a study to investigate how gastrointestinal factors, stress, physical activity and other factors may affect the prevalence and intensity of menopause symptoms.

Study Overview

A cross-sectional study was conducted to determine if there were any significant correlations between gastrointestinal symptoms and perceived stress levels and menopausal symptoms such as gynecological health, vasomotor symptoms (hot flashes, night sweats), sleep and physical activity in women who were in pre-menopause, peri-menopause and post-menopause reproductive stages. The study enrolled 693 women participants who were approximately between 47-53 years of age, and analyzed their responses using the Perceived Stress Scale (PSS) and Menopause-Specific Quality of Life Questionnaire (MENQOL).

Key Findings

It was found that age and reproductive stage, perceived stress, body mass index (BMI), physical activity, diagnosis of depression or anxiety disorder, and some gastrointestinal symptoms (such as frequency of defecation, and Bristol stool consistency) had a significant association with the intensity of menopausal symptoms, especially the vasomotor symptoms of hot flashes and night sweats. The study authors reported that further research is needed to confirm the relationship between stress, gastrointestinal, and menopausal symptoms.

Reference

Menopause (2023):10.1097/GME.0000000000002259, October 3, 2023. | DOI: 10.1097/GME.0000000000002259

Coming soon

A pragmatic approach to

management of menopause

Source: Canadian Medical Association Journal
May 15, 2023

A recent article published by the Canadian Medical Association Journal recommends hormone replacement therapy (also known as HRT) as the first line of treatment for menopause patients who do not have health risk factors. The article also explains other hormonal and non-hormonal solutions to manage menopausal symptoms.

Link to Full Article

Coming soon

Hormone therapy should be offered to more women with

severe menopause

Source: CBC News
May 15, 2023

CBC News recently interviewed Dr. Iliana Lega, an endocrinologist at Women’s College Hospital in Toronto who is the lead author of a new Canadian Medical Association Journal (CMAJ) article entitled: “A pragmatic approach to the management of menopause”, which discusses the benefits and risks of hormone therapy to manage severe menopause symptoms.

Link to Full Article

Photo Image obtained from CBC News article (sourced by S_L/Shutterstock).

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Menopause

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The Silent Burden: Iron Deficiency and Anemia in Women

By Henry Xu, Ph.D Reviewed by Joanne Tejeda, PhD and Rina Carlini, PhD original post: July 2, 2024 | updated: Sept 16, 2024

Interpretation of Serum Ferritin Test Results ( Per New Ontario Guidelines)

Association of cortisol in women with biomarkers of Alzheimer’s risk

Reviewed by Rina Carlini, PhD April 22, 2024

Stress, age, BMI and gastrointestinal factors are associated with severity of menopause symptoms

Reviewed by Rina Carlini, PhD October 13, 2023

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Photo Image obtained from CBC News article (sourced by S_L/Shutterstock).

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original post: July 2, 2024 | updated: Sept 16, 2024

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