There is a therapy that reduces hot flushes, improves sleep, protects bones, can lower cardiovascular risk (in women under 60 or within the first 10 years of menopause), and can have a significant impact on quality of life during menopause. And yet it is one of the most debated and misunderstood therapies in clinical practice, in Italian consulting rooms, the most feared and most often refused before it is even properly evaluated.
It is called hormone replacement therapy, abbreviated HRT. For decades it was at the centre of scientific controversies, alarming headlines and widespread fear. Today, thanks to twenty years of subsequent research, the picture is much clearer. And the international scientific community, from the International Menopause Society to the European Menopause and Andropause Society, is broadly in agreement: for the right women, at the right time, with the right formulation, the benefits far outweigh the risks.
This article is designed to explain everything you need to know in order to have an informed conversation with your doctor, without alarmism and without oversimplification. HRT is not the right choice for everyone, but it deserves to be understood.
What is hormone replacement therapy and how does it work
Hormone replacement therapy is a pharmacological treatment that supplements the hormones, primarily estrogens and progestogens, that the ovaries progressively stop producing during menopause. The basic principle is straightforward: replenish what is missing in order to reduce the symptoms caused by hormonal deficiency and protect the organs and tissues that depend on estrogens and progesterone to function well.
Estrogens, as we explained in the article on the role of the estrogen hormone in women's health, have receptors in almost every tissue in the body: brain, heart, bones, skin, mucous membranes, blood vessels. When their levels decline significantly, the systemic response can be wide-ranging. HRT acts on this mechanism upstream, before symptoms and risks become established.
In women with an intact uterus, estrogens are always combined with a progestogen (micronised natural progesterone or synthetic progestogens), to protect the endometrium from the risk of hyperplasia that would occur with unbalanced estrogens. In women who have undergone hysterectomy, the therapy can often be conducted with estrogens alone.
Beyond endometrial protection, progesterone, in particular micronised progesterone, has significant systemic effects. Through its neuroactive metabolites, such as allopregnanolone, it acts on GABA-A receptors in the central nervous system, contributing to improved sleep, reduced anxiety and mood stabilisation. Some evidence also suggests a more neutral metabolic and cardiovascular profile compared to several synthetic progestogens.
The goal of HRT is therefore not only the control of symptoms, but the optimisation of long-term health in women with estroprogestinic deficiency. A fundamental aspect, often overlooked, is that there is no one-size-fits-all HRT. The type of hormone, the route of administration, the dose and the duration of treatment are personalised based on clinical history, symptoms, age and the woman's own preferences.
What HRT is used for: documented benefits
The benefits of hormone replacement therapy, when started within the appropriate time window, are documented by decades of research and confirmed by the most up-to-date international guidelines.
On the symptom front, HRT is the most effective therapy available for hot flushes and night sweats, with documented reductions of up to 70–90% in the frequency and intensity of vasomotor symptoms. It improves sleep quality, reduces irritability and mood swings, combats brain fog and difficulty concentrating. It treats vaginal dryness and improves sexual function. It reduces joint and muscle pain. As we explored in the article on sleep and perimenopause, sleep improvement at this stage has consequences that go well beyond daily comfort.
On the long-term prevention front, HRT, when started before the age of 60 or within 10 years of menopause, the so-called "window of opportunity", is associated with a reduction in cardiovascular risk, preserves bone density preventing osteoporosis and fragility fractures, and according to the most recent evidence may have a protective effect on the risk of dementia and cognitive decline. The concept of the window of opportunity is central: the same hormones have very different effects depending on whether they are started early or introduced many years after menopause.
The narrative review published in the International Journal of Molecular Sciences in 2025, which synthesised evidence up to September 2025, confirms that early initiation of HRT, within 10 years of menopause, is associated with a reduction in all-cause mortality and significant cardiovascular benefits.
The story that created so much fear: the WHI study
To understand why HRT is still so loaded with fear, we need to go back to 2002. That year, the Women's Health Initiative (WHI) study was published, a large American randomised clinical trial that seemed to demonstrate a significant increase in the risk of breast cancer, stroke and heart problems in women on hormone therapy.
The result caused a sensation. HRT prescriptions fell by 50% within a few months worldwide. Many women stopped the therapy without consulting their doctor. A generation of gynaecologists stopped prescribing it.
The problem is that the WHI study had limitations related to the population studied and the therapies used that were only fully understood in subsequent years. The women enrolled had an average age of 63, meaning they were far older than the optimal therapeutic window. The formulation used conjugated equine estrogens combined with medroxyprogesterone acetate (MPA), is not representative of modern formulations, in particular of micronised natural progesterone, which has a much more favourable safety profile. And the results in terms of absolute risk were much less dramatic than newspaper headlines suggested: the absolute increase was approximately 8 additional cases of breast cancer per 10,000 women per year.
As highlighted in the IMS 2024 White Paper, which reviewed all the controversies, the scientific community took over twenty years to recover the ground lost from that poorly communicated study. In the meantime, millions of women suffered from untreated symptoms out of fear.
Systemic HRT vs local HRT: two different tools
A distinction that many women are not aware of is that between systemic hormone therapy and local hormone therapy. They are two tools with very different objectives, mechanisms and safety profiles.
Systemic hormone therapy targets the entire body. The hormones enter the bloodstream and act on all tissues that have estrogen receptors. It is used to treat vasomotor symptoms such as hot flushes, sleep disturbances, mood, cognitive problems, and for the prevention of osteoporosis and cardiovascular risks. It can be administered orally (tablets), transdermally (patches, gels, sprays) or through subcutaneous implants (not widely recommended in Europe).
Local hormone therapy, described in detail in the article on local hormone therapies in menopause, acts only on the vaginal and urogenital tissue. It is used to treat vaginal dryness, painful intercourse, recurrent cystitis and urinary problems. It is administered locally as creams, suppositories, or very low-dose vaginal rings. Systemic absorption is minimal, which makes it safe in many situations where systemic HRT is not indicated, including in many cases of prior breast cancer.
This distinction is clinically very relevant: a woman who cannot or does not want to use systemic HRT can still benefit from local therapy to improve quality of life safely.
Routes of administration: why the transdermal route is often preferred
Not all methods of administering systemic HRT are equivalent. The oral route is convenient, but estrogens taken by mouth are metabolised by the liver before entering the bloodstream, with an effect on the coagulation profile that can slightly increase thromboembolic risk. The transdermal route, patches, gel or spray on the skin, bypasses hepatic metabolism and maintains more stable hormonal levels in the blood.
The IMS 2025 guidelines, the most up-to-date available, indicate that the transdermal route is generally preferable, particularly for women with thromboembolic risk factors, women with migraine or liver problems, and for women starting therapy after the age of 60.
For the progestogenic component, micronised natural progesterone, so-called bioidentical progesterone, has demonstrated a potentially more favourable safety profile compared to first-generation synthetic progestogens, particularly with regard to the risk of breast cancer. This is one of the most important distinctions that the WHI study could not contemplate, having used medroxyprogesterone acetate.
When it is indicated: who can use HRT
According to IMS and EMAS guidelines, systemic HRT is indicated primarily in the following scenarios:
-Symptomatic menopausal women, that is, those with significant hot flushes, major sleep disturbances, mood problems, joint pain or cognitive symptoms that compromise quality of life, within the age of 60 or within 10 years of the last menstrual period. This is the most common case and the one with the best risk-benefit ratio.
- Women with early menopause, before the age of 40, and women with premature menopause, between 40 and 45 years of age. In these cases the therapy is particularly important to reduce the long-term risks of osteoporosis, cardiovascular disease and cognitive decline that arise from prolonged exposure to estrogen deficiency. Therapy should be continued at least until the age of physiological menopause.
- Women with high risk of osteoporosis and fragility fractures, in whom HRT represents an effective preventive strategy.
The assessment of the indication always requires a specialist consultation with a gynaecologist or endocrinologist with specific training in menopause. The decision is not made on the basis of symptoms alone, but on the basis of a complete clinical picture that includes personal and family history, cardiovascular risk factors, bone densitometry where indicated, glycolipid profile and the woman's own preferences.
In symptomatic women under 60 or within 10 years of menopause, the benefit-risk ratio of HRT is generally favourable when the therapy is prescribed for appropriate indications. The therapeutic decision should always be based on a shared decision-making process between doctor and patient.
Follow-up includes an annual assessment of cardiovascular risk, bone health, mammography according to national screening, and review of the therapeutic indication.
Who cannot use HRT: contraindications
The absolute contraindications to systemic HRT are clear and shared by the main international guidelines.
Systemic HRT must not be prescribed in case of: active breast cancer or prior history of hormone-dependent breast cancer, untreated endometrial cancer, vaginal bleeding of undiagnosed cause, prior stroke or TIA, active or prior venous thromboembolism not adequately evaluated (e.g. deep vein thrombosis or pulmonary embolism), active coronary heart disease, severe liver disease, porphyria.
There are also situations that require careful and personalised evaluation rather than automatic refusal: severe hypertriglyceridaemia, diabetes mellitus, severe obesity, migraine with aura, certain hypercoagulability conditions, family history of breast cancer. In these cases the transdermal route and natural progesterone can significantly modify the risk profile.
One important point is worth highlighting: a prior diagnosis of breast cancer is not automatically an absolute contraindication to low-dose local vaginal therapy, which has minimal systemic absorption. This is a topic that must be discussed case by case with the oncologist and the gynaecologist, but the most recent evidence, including a JAMA Oncology 2024 study on 49,237 patients, suggests that local vaginal therapy does not increase breast cancer-specific mortality.
Myths and realities about HRT: the most frequently asked questions
In this section we answer the questions women ask most often, dismantling the most widespread myths with the most recent scientific evidence.
Does HRT cause breast cancer?
The relationship between HRT and breast cancer is the most discussed and most misunderstood topic. The correct answer is: it depends on the formulation, the duration, the individual history and the age at which therapy is started.
HRT with estrogens only in women who have undergone hysterectomy does not increase the risk of breast cancer, and some studies even suggest a reduction in risk. Combined HRT with estrogens and synthetic progestogen (such as the MPA used in the WHI) is associated with a small increase in risk with prolonged use beyond 5 years. HRT with micronised natural progesterone has a much more favourable profile.
EMAS, in the summary document on breast cancer risk and hormone therapy 2022, clarified that regular alcohol consumption, obesity and physical inactivity increase the risk of breast cancer by 32–46%, 26–152% and 7–33% respectively, much more than any HRT formulation.
Does HRT cause weight gain?
No. HRT is not associated with significant weight gain compared to the natural increase related to age. Some women report mild fluid retention in the first few weeks, which resolves spontaneously. On the contrary, hormone therapy, particularly via the transdermal route, can contribute to reducing the abdominal visceral fat that accumulates during menopause, improving body composition. As we explained in the article on menopause belly, this accumulation is driven by hormones, not by diet.
Does HRT have to be taken for the minimum time possible?
This was the recommendation from previous guidelines, influenced by the WHI. More recent guidance has evolved. The IMS and EMAS today indicate that duration must be personalised based on symptoms, individual benefits and risks, with periodic reassessment of the risk-benefit ratio and without arbitrary time limits. For many women, a treatment of 5–10 years is appropriate and safe. For women with early or premature menopause, therapy should continue at least until the age of physiological menopause.
Does HRT protect the heart?
Within the window of opportunity, before age 60 or within 10 years of menopause, observational evidence shows a reduction in cardiovascular risk. This concept is known as the "timing hypothesis", according to which the cardiovascular effect of estrogens depends on age and timing of therapy initiation. A 2024 meta-analysis documented improvements in endothelial function with the use of MHT. Protection is more pronounced with the transdermal route. HRT is not, however, recommended as a primary or secondary cardiovascular prevention therapy, and its use after age 60 in previously untreated women requires great caution.
Can I stop HRT whenever I want?
Yes, but gradually. Abrupt discontinuation can cause a return of symptoms. It is advisable to progressively reduce the dose over time. The decision to stop should be taken with the specialist, not independently.
Is HRT the same as bioidentical hormones?
The term "bioidentical hormones" is often used imprecisely. The transdermal estrogens and micronised natural progesterone available through ordinary medical prescription are already bioidentical, meaning they have the same chemical structure as the hormones produced by the body. The so-called "compounded bioidentical" preparations made at the pharmacy do not follow the same quality and dosage standards as registered medicines, and are not recommended by the main scientific societies.
What are the undesirable effects and real risks of HRT?
Like any pharmacological therapy, hormone replacement therapy can have undesirable effects and risks. It is important to distinguish between relative risk and absolute risk, because individual risk in healthy women generally remains low.
The most common side effects are generally mild and transient and include breast tenderness, spotting in the first months of combined therapy, mild fluid retention, headache and nausea. These symptoms tend to reduce with adjustment of dose or formulation.
The most discussed risk is that of breast cancer. Follow-up data from the Women's Health Initiative indicate that combined estrogen-progestogen therapy is associated with approximately 8 additional cases of breast cancer per 10,000 women treated per year after approximately 5 years of use. This risk appears lower with micronised progesterone compared to some synthetic progestogens, although the data come primarily from observational studies.
Regarding venous thromboembolic risk, oral therapy is associated with approximately 2–3 additional events of deep vein thrombosis or pulmonary embolism per 1,000 women treated, especially in the first years of therapy and in women with risk factors. The absolute risk remains low in healthy women under 60. The transdermal route, on the other hand, does not appear to significantly increase thrombotic risk compared to the general population.
It is important to highlight that many modifiable risk factors, such as obesity, physical inactivity and alcohol consumption, contribute to the risk of breast cancer and cardiovascular disease to an equal or greater extent than hormone therapy itself. For this reason, the assessment of the risk-benefit ratio must always be personalised and periodically reviewed.
What are the alternatives to HRT and what are their limitations?
For women who cannot or do not wish to take hormone replacement therapy, there are non-hormonal options that can help manage some symptoms of menopause. It is important to know, however, that these alternatives act primarily on specific symptoms and not on the systemic estrogen deficiency that characterises menopause.
For vasomotor symptoms, drugs such as SSRIs and SNRIs (paroxetine, escitalopram, venlafaxine), gabapentin and the recent NK3 antagonist fezolinetant can reduce the frequency of hot flushes by approximately 30–60%, compared to the 70–90% achievable with HRT. These drugs do not, however, have significant effects on bone loss, the genitourinary syndrome of menopause, or the cardiometabolic profile.
Urogenital symptoms such as vaginal dryness, painful intercourse and urinary symptoms can be treated with lubricants, vaginal moisturisers or selective drugs such as ospemifene. These options are generally less effective than local estrogen therapy in restoring vaginal tissue trophism and do not modify the pathophysiology of urogenital atrophy.
From the perspective of bone health, drugs such as bisphosphonates, denosumab or SERMs can reduce the risk of fractures in high-risk women. These therapies are indicated in specific contexts and do not improve other symptoms of menopause, nor sleep quality or vasomotor symptoms.
On the metabolic and cardiovascular front, lifestyle modifications (physical activity, nutrition, weight control, smoking cessation) remain fundamental and are recommended for all women, regardless of HRT use. These interventions, however, do not replace the biological effects of estrogens on endothelial function, body fat distribution and bone metabolism.
It is also worth considering that non-hormonal alternatives can also have undesirable effects: antidepressants can cause sexual dysfunction and sleep disturbances, gabapentin sedation and dizziness, bone anti-resorptive drugs gastrointestinal effects or rare adverse events such as mandibular osteonecrosis in prolonged treatments.
For this reason, international guidelines agree that non-hormonal therapies represent valid alternatives when HRT is contraindicated or not desired, but when hormone therapy is indicated and there are no contraindications, it remains the most effective treatment because it is the only one that acts simultaneously on vasomotor symptoms, urogenital health and the prevention of menopause-related bone loss.
Hormone therapy is not enough on its own: the role of lifestyle
One of the most common mistakes, both on the part of women and some doctors, is thinking of HRT as a standalone solution. The most recent international guidelines, including the IMS White Paper on lifestyle medicine in menopause 2025, are explicit: hormone therapy works better, and in some cases is necessary, within a health journey that includes structural lifestyle modifications.
Physical activity is probably the second most important intervention after hormone therapy for health in menopause. As we explored in the article on physical activity in menopause, resistance training and HIIT are the most effective approaches for visceral fat, bone density and cardiovascular health. HRT and physical exercise have synergistic effects, not alternative ones.
Nutrition plays an equally relevant role, particularly in the management of body weight, systemic inflammation and bone health. Adequate protein, anti-inflammatory foods, and reduced refined sugars and alcohol are not optional at this stage: they are structural components of the health journey.
Psychological support, when necessary, is a dimension that is often underestimated. The menopausal transition has a significant emotional and identity impact for many women. As documented in the article on menopause as a cultural phenomenon, the cultural context and relational support profoundly influence the experience of symptoms.
Sleep deserves specific attention. Night sweats and estrogen deficiency compromise sleep architecture in a biological way. HRT can improve sleep significantly, but it needs to be integrated with adequate sleep hygiene and, when necessary, cognitive-behavioural support.
Pausetiv's approach is built on exactly this multidisciplinary vision: gynaecology, endocrinology, nutrition, sports medicine and psychological support are not separate compartments, but integrated levers of a single journey. Hormone therapy, when indicated, is a powerful tool. But it works best when it is part of a broader plan.
How to understand whether HRT is right for you: the concrete steps
If you are reading this article wondering "is it right for me?", the honest answer is: you cannot know alone, and no article, however comprehensive, can answer on behalf of a personalised clinical evaluation.
What you can do now is arrive at your consultation with the right information. Make a note of the symptoms you are experiencing, their frequency and intensity. Reconstruct your family history for breast cancer, cardiovascular disease and osteoporosis. Bring your most recent blood tests, in particular lipid profile, blood sugar, hormones if available. If you have had a bone densitometry, bring it along.
A consultation with a gynaecologist or endocrinologist experienced in menopause, such as those available on Pausetiv, makes it possible to evaluate indications, contraindications, the most suitable formulation and to build a plan that respects your history and your goals. Book a consultation.
HRT is not a choice made out of fear or fashion. It is an informed, personalised medical choice that can have a very concrete impact on how you experience this phase of life and how you present yourself at 60, 70 and 80 years of age.
Do you want to understand whether hormone therapy is right for you?
Book a consultation with a Pausetiv specialist.
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