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Hormone Replacement Therapy


The 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. 

Introduction of Hormone Replacement Therapy for Menopause

Reviewed by Rina Carlini, Ph.D and Joanne Tejeda, Ph.D
July 20, 2023

Hormone replacement therapy (HRT) is a treatment commonly used to manage and relieve menopause-related symptoms such as hot flashes, night sweats, headaches, sleep disturbance, vaginal dryness, mood swings and irritability, among others [1–6]. During the menopause transition (a.k.a. perimenopause), these symptoms occur as a result of low estrogen and progesterone levels in the body [1–6]. HRT is often prescribed as the first line treatment of vasomotor symptoms such as hot flashes and night sweats in menopausal women who have no history of other medical conditions [1,2,7].  However HRT might not be recommended if you have had one or more of the following health conditions [1,2,7]:

  • Breast cancer

  • Coronary artery disease

  • Thromboembolic disease (Deep vein thrombosis)

  • Stroke

  • Undiagnosed vaginal bleeding

  • Endometrial cancer

  • Endometriosis

Estrogen deficiency due to menopause can cause significant loss of bone mass, resulting in osteoporosis [1,8,9]. Osteoporosis is a systemic skeletal condition seen by low bone density, deterioration of the bone tissue and decreased bone strength which leads to bone fragility and increased risk of fractures [1,8,9]. HRT is normally used as a secondary line of treatment for the prevention of osteoporosis in menopaused women [1,8,9]. However a recent article published in the Canadian Medical Association Journal reported that HRT is the treatment of choice for peri-menopausal women who are in their 40s and 50s experiencing vasomotor symptoms (i.e., hot flashes and night sweats) within 10 years of their final menstrual period [1]. The duration and dosage of treatment is dependent on the individual and is no longer recommended to be limited to the first 5 years of taking HRT [1].

How does Hormone Replacement Therapy (HRT) Work?

The main purpose of HRT during menopause is to restore estrogen and progesterone hormones in females to normal levels [10]. Usually, HRT treatments are delivered as a combination of estrogen and progestin – which is the synthetic version of the hormone progesterone [1,6,11]. Estrogen is prescribed to manage menopause symptoms, while progestin works primarily to protect the tissue lining of the uterus from becoming enlarged or inflamed, or to prevent endometrial cancer, and also in managing menopause symptoms [1,6,11]. The types of estrogen hormone used in HRT can include estradiol 12 (most prescribed), ethinylestradiol, mestranol, esterified estrogens (estradiol valerate), estropipate, and conjugated equine estrogens (CEE) [11]. The types of progesterone hormone used in HRT can include progestin (synthetic progesterone), medroxyprogesterone acetate (MPA), levonorgestrel, norethindrone, desogestrel, and micronized progesterone and others [13,14]. 


For those who are scientifically curious, here is a visual representation of the structural differences between naturally occurring estrogens and progesterone and their synthetic counterparts. If organic chemistry does not interest you, please skip this section to continue learning about HRT.














Please consult with your medical doctor or naturopathic doctor to discuss the benefits and risks of Hormone Replacement Therapy as a way to manage your menopause hormonal health.

Types of Hormone Replacement Therapy and Delivery Formats [1,3,15]: 

  1. Estrogen-Progestin Combination – for individuals that have a uterus

    • Oral pills

    • Transdermal patch (applied outside of upper arm, lower stomach, or top of the buttocks)

  2. Estrogen Only – for individuals who have had a total hysterectomy [1]

    • Transdermal patch (applied to outside upper arm, lower stomach, or top of the buttocks)

    • Transdermal gel (applied to the forearm)

    • Transdermal spray (applied to the forearm)

    • Vaginal creams, tablets, or rings

  3. Oral pills

  4. Progestin Only – for individuals with an adverse reaction to estrogen [16]

    • Oral pills

    • Intrauterine device (IUD) (e.g., Levonorgestrel (Mirena®)) [1,17,18]

For individuals that are recommended to take progesterone but are not interested in taking synthetically made progestin, there is the option of taking oral micronized progesterone (Prometrium®) [19].

Hormone Replacement Therapy Benefits [1,2,6]

  • Improves up to 90% of vasomotor symptoms in patients with moderate to severe hot flashes [1].

  • Improves sleep quality by lowering mood disturbances and reducing night sweats

  • Relieves vaginal dryness (a.k.a. vaginal atrophy) and increases libido (sexual drive)

  • Lowers the risk of osteoporosis-related fractures such as hip fractures (up to 34% decreased risk), vertebral fractures (up to 23% decreased risk) [1]

  • Improves insulin sensitivity and reduces the risk of type II diabetes

  • Reduces the risk of coronary artery disease in women who start HRT before their 60’s.

  • Improves overall quality of life, sleep, and relationships with family, spouse/partners, friends [1,2,20]

Risks of Hormone Replacement Therapy

Over the past two decades, HRT has been the subject of many medical debates and controversies because of the flawed conclusions that were reported as outcomes from a large USA population health research study published in 2002 known as the Women’s Health Initiative (WHI) study [1,21–23].  The authors of the WHI study reported that HRT could lead to detrimental health risks, and specifically higher risk of breast cancer, than health benefits for women aged 65 years or older, who were the subject of the study [1,21–23]. These negative results were widely publicized among the medical community and popular media, which ensued panic among women patients, and triggered lawsuits [1–3,7,11,22]. 

However, by 2006 the conclusions of the WHI study had been debunked because of new clinical studies which proved that the use of HRT by younger women entering perimenopause or in the early post-menopause years, led to a reduced risk of coronary disease, osteoporosis, endometrial cancer, and a lowered the risk of poor cognitive health [1–3,7,11,22]. Unfortunately a huge generation of ‘babyboom’ and ‘GenX’ women, many of whom are currently in their 50s to 80s, were negatively impacted by the false outcomes originally reported from the WHI study, since many physicians in the Western, developed world chose to avoid prescribing HRT to many women who could have greatly benefited from this therapy during their menopausal journey [1–3,7,11,22]. 

It is important to note that from both the 2002 WHI study and new clinical studies, it remains true that for women over the age of 60, HRT can present more risk of health complications rather than benefit, so it is usually not recommended to women in this older age group [1–3,6,7,11,20,22,24]. 

There has also been research that has associated estrogen-progestin HRT with an increased risk of dementia and Alzheimer’s disease even in women aged 55 and younger although more research needs to be done in order to determine if the increased risk comes from HRT or from a natural predisposition to these diseases [25]. 

Hormone Replacement Therapy and Cancer


A review of all clinical studies looking at HRT and cancer patients and survivors published in the Cancer Journal in 2022, found that out of 25 studies published between 1980 and 2013, only 1 study (the hormonal replacement therapy after breast cancer (HABITS) trial) demonstrated an increased risk of cancer recurrence (colorectal and local cancer but not breast cancer) [24,26].  However, that study was prematurely stopped in 2003 and so its results were misinterpreted and misrepresented to mean that HRT should not be recommended to cancer survivors [24].


Despite the above stated research, according to the North American Menopause Society (NAMS), for breast cancer survivors, systemic estrogen HRT (one that circulates estrogen in the bloodstream), is not recommended for relief of hot flashes [27]. 


However, both the NAMS and the SIGMA Canadian Menopause Society acknowledges that estrogen HRT is associated with little impact on breast cancer risk and that with prolonged use, there is a slight increase in risk [28,29]. In order to minimize risk, the NAMS recommends starting with the lowest effective dose for the shortest time period possible [28]. 

Side effects of Hormone Replacement Therapy

Common side effects of HRT may include, but are not limited to [1,2,6]:

  • Headache

  • Vaginal bleeding (or breakthrough bleeding)

  • Premenstrual-like symptoms such as breast-tenderness, bloating, mood swings can persist within the first few months of starting HRT [13]

  • Breast pain (Mastalgia)

  • Weight change

  • Cholecystitis (inflammation of the gallbladder)

  • Blood clots in the legs and lungs [20]


The duration of hormone therapy as well as the format will vary depending on the symptoms and personal preferences, along with the risk profile of the woman [6].

If you are interested in learning more about the impact of the 2002 WHI study, please see the following resources that feature Dr. Avrum Bluming, a USA gynecologist, hematologist, medical oncologist who has written extensively and was interviewed on many podcasts about the negative fallout of the study as well as Dr. Louise Newson, A U.K. general practitioner and Menopause Specialist:

  • Podcast – “Avrum Bluming, M.D. and Carol Tavris, Ph.D.: Controversial topic affecting all women—the role of hormone replacement therapy through menopause and beyond—the compelling case for long-term HRT and dispelling the myth that it causes breast cancer” available at

Please consult with your doctor to determine if Hormone Replacement Therapy is right for you.



Menopause, hormone therapy, vasomotor symptoms, hot flashes, estrogen, progestin, progesterone, hot flashes, night sweats, vaginal bleeding, cancer, women’s health, hormonal health


Figure 1. Chemical structures of natural and synthetic estrogens and progesterone.


To view the list of references, click on the plus symbol 

Evaluating the safety of estrogen route of administration when using hormone therapy for relieving menopause symptoms

Reviewed by Rina Carlini, PhD, Joanne Tejeda, PhD and Azi Nia, PhD
October 18, 2023

The majority of women worldwide struggle with menopausal symptoms, which can include hot flashes and/or night sweats (vasomotor symptoms), mood changes (anxiety, depression), vaginal dryness (genitourinary symptoms), irregular and/or heavy menstruation, weight gain, thyroid disorders (metabolic symptoms), anemia (low iron stores), fatigue and hair loss, joint pain (musculoskeletal symptoms), irritable bowel (gastrointestinal symptoms), dry skin, dry eyes, insomnia and others [1]. Unfortunately, only a quarter of women in the USA actually seek treatment options to manage their symptoms, which indicates that the conversion about how to get qualified menopause care should be amplified in every family household and workplace setting.

The Menopause Society (formerly known as the North American Menopause Foundation) and also the Canadian Menopause Society have advocated that a first line of treatment for relief of menopausal symptoms and complications is Hormone Therapy, or HT [2]. HT can be administered as either estrogen-progesterone combination therapy, progesterone-only therapy, or estrogen-only therapy.

Recently, a large population health clinical study was conducted in Alberta, Canada involving more than 112,000 women aged 45 years or older to examine the safety of the various formats and routes of administration for estrogen-only hormone therapies, which included oral pills, transdermal patches, and vaginal creams [3]. The clinical study enrolled women who had used at least two consecutive treatments of estrogen-only HT during the period of 2008 to 2019, and the primary outcome of the study was to evaluate the risk of developing high blood pressure (incident hypertension) [3]. The effect of the source of estrogen being taken – where the majority of study participants were taking either conjugated equine estrogen (CEE; 40%) or synthetic estradiol (55%), and a minority of participants were taking synthetic estrone (5%) –  was also investigated.

The key findings learned from the study:

  • Women taking oral estrogen had a 14% higher likelihood of developing hypertension than those using transdermal estrogen.


  • Women taking oral estrogen had a 19% elevated risk of developing hypertension compared to women using vaginal estrogen creams. This association was more notable in women below the age of 70 years.


  • No differences in the risk of hypertension were observed for the study participants taking either transdermal or vaginal estrogen across all age groups.


  • When comparing the two different sources of estrogen, conjugated equine estrogen was linked to an 8% heightened risk of high blood pressure.


  • Higher daily estrogen dose in oral form, compared with the same dose in transdermal and vaginal forms, was associated with a significantly greater risk of hypertension.


  • Long-term administration of any form of estrogen-only HT may increase the risk of developing hypertension.

To reduce the risk of developing hypertension while managing menopausal symptoms, a physician may prefer to prescribe estrogen HT treatment delivered as a transdermal patch or vaginal cream rather than the oral pill. The study also emphasized that HT treatment is  prescribed by a physician based on the specific needs and health profiles of each individual. Most women who are already taking oral estrogen – and are at low risk of developing hypertension – can continue their estrogen-only HT safely based on the recommendations and health monitoring by their physician.

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Download Clinical Study article


[1] Santoro, N., Roeca, C., Peters, B. A., & Neal-Perry, G. (2021). The Menopause Transition: Signs, Symptoms, and Management Options. In Journal of Clinical Endocrinology and Metabolism, 2020, 106, 1-15.

[2] The 2022 hormone therapy position statement of The North American Menopause Society. Menopause: The Journal of The North American Menopause Society, 2022, 29, 767-794. DOI: 10.1097/GME.0000000000002028

[3] Kalenga, C. Z., Metcalfe, A., Robert, M., Nerenberg, K. A., Macrae, J. M., & Ahmed, S. B. (2023). Association between the Route of Administration and Formulation of Estrogen Therapy and Hypertension Risk in Postmenopausal Women: A Prospective Population-Based Study. Hypertension, 2023, 80, 1463-1473.

HRT Article 2

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Mithra and Searchlight Pharma announce Donesta® licensing agreement for Canada

Source: Mithra Women's Health
June 28, 2023

Mithra, a Belgian biotech company specializing in women's hormonal health therapeutics, has licensed their natural estrogen therapy, Donesta (estetrol), to Montreal-based Searchlight Pharma Inc. for the Canadian market. Donesta is an investigational medicine for menopause symptoms based on Estetrol (E4), a unique estrogen with distinctive biological mechanisms. Clinical trials of Donesta have shown encouraging efficacy results, including a significant reduction in menopause symptoms, and phase 3 trials have supported regulatory submissions in the US and Canada. The partnership aims to provide Canadian women with an improved treatment option for managing menopause symptoms effectively. 

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