Estrogen is the main female sex hormone. Before menopause, your ovaries make most of it. Two kinds of cells in the ovary work together: one makes a building block, and the other turns it into estrogen. The egg sac that is growing each month (the follicle) makes the most.¹

Your body has three main forms of estrogen:

• Estradiol is the strongest form, and the main one before menopause.²
• Estrone is weaker. After menopause it becomes the main estrogen in your blood, because body tissues make it from other hormones once the ovaries have stopped.^3,2
• Estriol is the weakest.²

The estrogen we use is estradiol, exactly the same molecule your ovaries made.⁴ If you ask us about “natural” or body-identical hormones, this is what we mean.

• The transition lasts about 4 years on average. As the number of eggs falls, the brain signal hormone FSH (follicle-stimulating hormone) rises and swings from month to month. Estrogen also swings, and in some months it is higher than before. Ovulation becomes less common from about 5 years before the last period, so progesterone falls first.³
• The late transition. Once periods start to skip for more than 60 days, low estrogen takes over. Bone starts to thin, and hot flushes and vaginal dryness become clearly more common.³
• Menopause means no period for 12 months in a woman over 45. Half of women reach menopause by 52.³ If the ovaries stop before 40, this is called premature ovarian insufficiency; between 40 and 44 it is called early menopause.⁵
• Symptoms often come before estrogen falls. In the large SWAN study, 45% of women had higher estradiol in the 5.5 years before menopause than earlier. Most symptoms, such as hot flushes, brain fog and lower sex drive, started early in the transition, while estrogen was still adequate.⁵ This is why, if you still have periods, we decide by your symptoms and not by your estradiol level.

• Reproductive years: Periods: Regular; Estrogen: Rises and falls with each cycle; Progesterone: Made every cycle after ovulation
• Early transition: Periods: Cycle length changes; Estrogen: Swings, some months high; Progesterone: Missing in cycles without ovulation
• Late transition: Periods: No period for more than 60 days; Estrogen: Mostly low; Progesterone: Very little
• After menopause: Periods: None for 12 months; Estrogen: Low (estrone takes over); Progesterone: Almost zero

The pattern of a woman’s hormones from the reproductive years to after menopause. This is an illustration, not real values.^3,5

The age of menopause, and our rules linked to age.^3,5,6

Estrogen receptors are found throughout the body, including the vagina, urethra and bladder,³ and the cells of connective tissue such as skin.⁵

• Brain and hot flushes. Estradiol keeps a group of nerve cells in the temperature centre of the brain in check. When estrogen falls, these cells become overactive and trigger hot flushes.³
• Bones. Low estrogen speeds up the breakdown of bone. The International Menopause Society calls estrogen the body’s natural treatment against osteoporosis. From 1 year before to 2 years after the last period, the spine loses about 10.6% of its bone and the hip about 9.1%.⁵
• Skin. In the first 5 years after menopause, skin loses about 30% of its collagen, and then about 2.1% each year over 15 years.⁵

Estrogen tablets pass through the liver first. There they are changed into estrone and change the liver’s production of clotting proteins. Estrogen gel on the skin skips this first pass through the liver.⁵

• Blood clots. In a large UK study, hormone tablets raised the risk of clots in the veins, but estrogen on the skin did not.⁷ The International Menopause Society concludes that estrogen on the skin does not raise this risk, even in women who are overweight, have an inherited tendency to clot, or have had a clot before.⁵
• Blood fats. Tablets raise triglycerides (a type of blood fat); gel hardly does.^8,5
• Testosterone. Tablets raise a binding protein that lowers active testosterone; gel has very little effect.⁴

This is why we use only estrogen gel on the skin. It carries a lower risk of clots, it can be used if your triglycerides are high, and it does not lower your free testosterone.

• Hot flushes and night sweats. About 80% of women have them, and about 1 in 3 have moderate to severe symptoms. They last a median of 2.6–7.4 years, shorter in Asian women, and 40.1% of women still have them after 60.⁵ A hot flush is a sudden feeling of heat with red skin and sweating, because blood vessels in the skin widen to release heat. A night sweat is the same thing during sleep.⁵
• Joint and muscle aches. After hot flushes, these are the most common symptom, affecting more than 65% of women.⁵
• Skin changes, in 60–70% of women.⁵
• Vaginal dryness, which doubles by the late transition, and pain during sex.^5,3
• Brain fog and lower sex drive, from early in the transition.⁵
• Low mood, poor sleep and anxiety. The late transition is a time of higher risk for new depression and sleep problems.³

Physicians who focus on optimal hormone levels look for a wider range of signs: tiredness that does not go away, low mood, low sex drive, poor memory, light sleep, sagging breasts, irregular or light periods, recurrent bladder infections, leaking urine when you cough or sneeze, a dropped womb or bladder, joint pain, dry eyes and mouth, and fine lines above the upper lip and at the corners of the eyes. These signs have many causes. Your doctor looks at the whole picture with you.

You need to know these, because they help us adjust your dose:^2,4

• sore, tender or swollen breasts
• bloating
• water retention, swollen hands or feet, a puffy face
• unusual bleeding, spotting or heavy periods
• more vaginal discharge
• headache, nausea or tummy pain
• weight change

Physicians who focus on optimal hormone levels add feeling tense, anxious or irritable, poor sleep, and acne. If you notice any of these, tell us.

“Clinical trials” means the result comes from randomised trials. “Early research” means smaller or observational studies.

• Hot flushes and night sweats (clinical trials). Estrogen is the most effective treatment. It reduces how often they happen by 75% compared with a dummy treatment, and low to moderate doses relieve them in more than 80% of women after menopause.⁵ In the KEEPS trial, after 6 months, moderate to severe symptoms remained in 6.7% of women using estradiol on the skin, compared with 28.6% on a dummy treatment.⁹ Improvement can start within 2 weeks.¹⁰
• Sleep (clinical trials). Estrogen helps sleep in women with hot flushes,⁵ and estradiol on the skin may improve sleep quality in the years around menopause beyond its effect on hot flushes (lower-quality evidence).^5,4
• Vaginal dryness and pain during sex (clinical trials). Hormone treatment helps vaginal thinning, although 10–15% of women using whole-body treatment still have some vaginal symptoms.¹⁰ Overall sexual function improves a little.⁵
• Bones (clinical trials). Estrogen is a first-choice treatment to prevent bone thinning after menopause and lowers fractures from osteoporosis.⁵ The fracture evidence comes from tablets; bone density is kept well with both tablets and low-dose skin treatment.⁵
• New diabetes (clinical trials). About 30% fewer new cases of diabetes than with a dummy treatment, mostly with tablets.^5,4
• Heart (clinical trials and early research, when started before 60 or within 10 years of menopause). The International Menopause Society concludes that heart disease and deaths from all causes are lower in this group.⁵ In the DOPS trial, started about 7 months after menopause, deaths, heart failure and heart attacks combined were about half as common.¹¹ In the ELITE trial, artery-wall thickening slowed only in women who started within 6 years of menopause.¹² These trials used tablets; low-dose estradiol on the skin in KEEPS did not change artery walls or calcium in the heart arteries.⁵
• Mood early in the transition (clinical trials). In women aged 45–60 with normal mood, an estradiol patch with body-identical progesterone cut new, clinically significant depressive symptoms from 32.3% to 17.3% over 12 months, only in women early in the transition.¹³ After menopause, estradiol on the skin did not improve mood in KEEPS.⁹
• Skin (early research). Small trials found estrogen prevents collagen loss, thickens the skin and reduces dryness.^5,4
• Joints (clinical trials). In the WHI trial, women on hormones had less joint pain and stiffness.^5,4
• Balance (early research). Small trials found balance improved within 3 months.⁴
• Bowel cancer (early research). Observational studies found fewer cases, but in WHI the drop was seen only with estrogen plus a synthetic progestin, and estrogen is not recommended to prevent it.⁵

Clinical trials so far have not shown that estrogen helps memory or prevents dementia, urine leakage or repeated bladder infections, weight, or anxiety, and it should not be used to prevent heart disease in women without symptoms.^5,2,14

Breast cancer is the biggest worry for most women thinking about hormones. We want you to have the full picture.

Breast cancer becomes more common with age, with or without hormones. Worldwide, new breast cancers rise from 75.5 per 100,000 women a year at age 40–44 to 126.4 at 50–54 and 190.8 at 75 and over.¹⁵ In Thai women, rates are highest at ages 55–69 (111.7 at 55–59) and fall after 70.¹⁶ Breast cancer is the most common cancer in Thai women.¹⁷ The age when women start estrogen is the age when breast cancer is already rising, so a cancer found while using hormones may be one that comes with age, or one that was already there before treatment. This is why we need a mammogram before you start.

New breast cancers by age, per 100,000 women per year, worldwide and in Thailand.^15,16

The type of hormone matters. Most studies suggest the risk depends more on the type of progestogen than on estrogen.^18,5 The exception is the Lancet 2019 analysis, which found no difference by type of progestogen and a small rise with estrogen alone.⁶

• WHI trial (USA), followed for more than 20 years¹⁹: Estrogen alone: Estrogen tablets (from horses) in women without a womb: breast cancer 22% lower, and deaths from breast cancer 40% lower; Estrogen with a progestogen: With a synthetic progestin: 28% higher, but deaths from breast cancer not clearly different
• Lancet 2019, worldwide data, 108,647 women with breast cancer⁶: Estrogen alone: A small rise; gel and tablets similar; Estrogen with a progestogen: Higher, and higher with a daily progestogen than with monthly courses
• E3N study (France), 80,377 women¹⁸: Estrogen alone: A small rise; Estrogen with a progestogen: With body-identical progesterone: no rise; with other progestins: higher

These studies have limits. The trials used tablets and a synthetic progestin, not our medicines. The data on estradiol gel and body-identical progesterone come only from observational studies, and no trial has been designed to answer this question.⁴

What about our medicines? The study closest to our treatment is E3N. There, estradiol on the skin with body-identical progesterone carried a risk not clearly different from no hormones. But the risk tended to rise with the number of years of use, and the Lancet 2019 analysis did find a higher risk with body-identical progesterone.^18,6 So we will not tell you that there is no risk at all. What we can say is that it looks lower than with synthetic progestins in some studies,²⁰ and the International Menopause Society agrees.⁵

Putting the risk in proportion. In Western women of average weight who never used hormones, the chance of breast cancer between ages 50 and 69 is 6.3%. With 5 years of hormones from age 50, this becomes 6.8% with estrogen alone (one extra case for every 200 users), 7.7% with estrogen plus a progestogen in monthly courses (one extra for every 70) and 8.3% with a daily progestogen (one extra for every 50).⁶ These numbers come mostly from synthetic progestins. The extra risk from hormone therapy is small, and the same as or lower than the extra risk from too little exercise, obesity or drinking alcohol.⁵ The risk rises with years of use and falls after stopping.^5,2

What we do to look after your breasts:

• A mammogram before you start and every year while you use estrogen.
• Only estradiol gel and body-identical progesterone, never synthetic progestins.
• We ask about your breasts at every visit, and review the benefits and risks with you every year.

If you have a womb, estrogen must always be balanced by progesterone. This is one of the most important parts of your treatment.

Estrogen makes the cells of the womb lining grow, so the lining becomes thicker.²¹ Without progesterone to balance it, there is nothing to stop the growth and nothing to signal the lining to shed. The lining keeps thickening, and over time this can lead to abnormal thickening of the lining (endometrial hyperplasia), and in some women to cancer of the womb lining.^21,22 The product label states that estrogen alone raises the risk of womb-lining cancer 2 to 12 times.²

This happens in two situations:

• Cycles without ovulation, in the years before menopause or with polycystic ovary syndrome (PCOS), when the body makes no progesterone.²¹
• Estrogen treatment without enough progesterone, when progesterone is missing, taken for too few days, or not taken regularly.^5,22

The good news is that this change is slow and takes years. The most common type of thickening turns into cancer in fewer than 5 in 100 women over 20 years, and most cases go away by themselves.²¹ This is why, when the lining is normal before you start, we can look after early bleeding calmly in our clinic.

What happens to the womb lining with and without progesterone. This is an illustration, not real values.^1,23,5

From our doctor Protecting the womb lining is one of the two pillars of how we give women’s hormones. The other is using body-identical hormones, the same hormones your body makes. I have met many women who were taking estrogen without enough protection for the womb lining, and who did not know they were at risk. For us, both pillars always go together.

How we protect it:

• Body-identical progesterone every night. Every woman with a womb who uses estrogen needs a progestogen; this is the strongest evidence for progesterone.⁵ You take the full protective amount every night, starting no later than the day you start estrogen. In studies where progesterone was taken with estrogen for 12–14 days each month, it protected the lining for up to 5 years.^5,24 When it is taken on only some days of each month for more than 5 years, the risk of womb-lining cancer rises,^25,5 which is one reason we give it every night. More about progesterone is on our progesterone page.
• Creams do not protect the womb. Progesterone cream on the skin cannot protect the womb lining, so it must never replace progesterone capsules when you use estrogen.^5,24
• Another way: a hormonal coil. A hormonal coil (levonorgestrel intrauterine system) protects the lining with any dose of estrogen, for 5 years. If you have one, you do not need progesterone capsules for protection.⁵ A gynaecologist fits it.

Putting the risk in proportion. A body mass index (BMI) of 40 or more raises the risk of womb-lining cancer about 10 times compared with a healthy weight.⁵ Overall, in women who use hormones at standard doses and have no abnormal bleeding, the risk of womb-lining cancer is below 1%.⁵

What raises the risk of womb-lining cancer. We ask about these before you start, because they change how we look after any bleeding. Several come from older or monthly-course hormone methods that we do not use, but you may have used them elsewhere before.^22,5

Major risk factors (one is enough)

• BMI of 40 or more
• Lynch or Cowden syndrome (inherited conditions that raise cancer risk)
• Estrogen without a progestogen for more than 6 months, with a womb
• A progestogen only every 3 months (an older method no longer advised) for more than 12 months
• Monthly-course hormones for more than 5 years, started at 45 or older
• Monthly-course progesterone on fewer than 12 days a month for 12 months or more

Minor risk factors (two or more count)

• BMI 30–39
• Diabetes
• Estrogen without a progestogen for 3–6 months
• The same for 6–12 months
• Cycles without ovulation, such as PCOS
• The same for 6–12 months
• Too little progestogen for the estrogen dose for more than 12 months, including an expired hormonal coil

We give estrogen to women aged 45 and over who have symptoms of low estrogen. We do not give it to women without symptoms to prevent disease. We use 45 because menopause before 45 counts as early, and needs a gynaecologist’s care.^3,5

• After menopause. If you have symptoms of low estrogen on the symptom questionnaire, and your doctor agrees they fit, we can start estrogen.
• Still having periods, and your cycles have started to change. We start estrogen only if you have hot flushes. If they are moderate, we start progesterone first, and add estrogen after 3 months if hot flushes continue. If they are strong or very strong, we start estrogen and progesterone together, because the symptoms affect your life too much to wait.
• Still having regular periods. We do not give estrogen, even with symptoms. Physicians who focus on optimal hormone levels explain that at this stage your estrogen is usually not missing, and in some months it is even higher than before; what falls first is progesterone, and sometimes testosterone. We look after you with those hormones instead.
• Vaginal dryness is your only symptom. We refer you to a gynaecologist. The main treatment for vaginal and urinary symptoms of menopause is estrogen placed in the vagina,⁵ which is not one of our medicines, and the gel on the skin is not the main treatment for this.

Some women we refer rather than treat. We tell you this now so you do not lose time:

• Under 45, or menopause before 45. If your ovaries stopped before 40, or both ovaries were removed before 45, hormones are needed to replace what was lost early, often at higher doses and until the usual age of menopause, whether you have symptoms or not.⁵ This needs a gynaecologist who follows you over time.
• Age 60 or over and starting hormones for the first time. This is not because you should not have hormones. It is because they should be started by a doctor who can look for causes and check for cancer directly, at an age when breast, womb and ovarian cancers are more common, and because hormones for hot flushes are recommended for women under 60 or within 10 years of menopause.⁵ If you already use our hormones when you turn 60, you can continue with us, and we review the benefits and risks with you every year.
• Breast, womb, ovarian or another hormone-sensitive cancer, now or in the past, including after successful treatment. The product label says not to use estrogen after breast cancer, guidelines do not recommend it,^2,5,10 and our treatment is for quality of life, not a treatment you cannot do without. If hormones are ever considered, it should be under a specialist, in a hospital. Please never buy hormones to use on your own in this situation.

Estrogen is suitable for many women, but it is not one size fits all. There are many things we need to know about you to choose the treatment that fits you. Some women need special consideration before starting; this does not always mean they cannot use estrogen. Our doctor checks these:

• Pregnancy or breastfeeding. We do not start.²
• Still having periods. Estrogen gel and progesterone are not contraceptives, and pregnancy at this age carries more risk of miscarriage, ectopic pregnancy and problems for the baby.⁵ We talk with you about contraception (see below).
• The combined contraceptive pill. It already contains estrogen, so with the gel you would get estrogen twice. You change to another method before starting.
• Vaginal bleeding that has not been explained. A gynaecologist needs to find the cause first.²
• Abnormal thickening of the womb lining that has not been treated. We do not start, and advise you to see a gynaecologist.²
• An abnormal or suspicious mammogram. We do not start, and advise you to see a specialist.²
• Breast cancer risk. If you have a high risk, for example a BRCA gene, a close relative with breast cancer, past radiation to the chest, or dense breasts, we do not start, and advise you to see a specialist.⁵
• A blood clot now, or a past stroke, heart attack or chest pain from the heart, however long ago. We do not start, and advise you to see a specialist, because hormones in this situation need a specialist involved in your care.^2,5
• A past clot that has healed, or an inherited tendency to clot. The label says not to use it, but the International Menopause Society concludes that estrogen on the skin does not raise the risk of clots even in this group. We can use the gel, and your doctor explains this to you.^2,5
• Blood pressure. We measure it before you start. High blood pressure that is not controlled, liver disease or abnormal liver tests, or very high triglycerides. We do not start; a specialist treats these first.^5,2,10
• Migraine, especially with aura (warning signs before the headache). We can use the gel, starting low and applying it every day without breaks.^5,2
• Fibroids, endometriosis, past thickening of the womb lining, diabetes, gallstones, lupus, epilepsy, asthma, or otosclerosis (an ear condition). We can use the gel, let the specialist who looks after the condition know, and keep a closer eye on it at each visit.²
• Heart or kidney disease. Estrogen can cause water retention, so we ask about swelling at each visit.²
• Hot flushes that started many years after menopause. These may have another cause, such as sleep apnoea or an overactive thyroid, so we look for it first.⁴
• Other hormones or products from elsewhere, such as other estrogens, the contraceptive pill or hormone creams, so you do not get the same hormone twice.

• Estradiol. We test it before you start as a baseline to compare against, not to decide whether you can have estrogen.
• FSH, only if your periods cannot tell us whether you have reached menopause, for example after a hysterectomy or with a hormonal coil. If you still have periods, the test is done on days 2–5 of your cycle. We do not test it while you use the gel, because the result cannot be read.^5,26
• Blood fats and liver tests from your entry hormone panel, because very high triglycerides have been linked with inflammation of the pancreas, and the label says not to use estrogen in active liver disease.²
• A mammogram before you start (a result from the past 12 months is fine) and every year while you use estrogen. The label says not to use estrogen if breast cancer is present or suspected, and the age when women start estrogen is the age when breast cancer is rising. A check before you start finds a cancer that was already there, rather than finding it during treatment.²
• A vaginal ultrasound and gynaecologist visit before you start, if you have a womb (a result from the past 12 months is fine). We do not start without it. More about this is on our progesterone page.
• Before your blood test, stop biotin for 72 hours, because it interferes with the test. If you still have periods, note the day of your cycle.

• Estrogen gel, every day, without breaks. Stopping for a few days each month lets hot flushes come back during the break and makes blood-test timing complicated, and the claim that breaks lower breast cancer risk has not been shown in research. The label and the International Menopause Society use it every day.^2,5 So we use it every day, all month.
• If you have a womb, progesterone every night as well (see “Protecting the womb lining”).
• Your doctor sets your dose and adjusts it at your follow-up visits. We start low. If you still have symptoms at a follow-up visit, your doctor may raise the dose one step at a time. We do not raise it before the visit, because low doses take time to work fully: after 12 weeks, more than 80% of women have clearly fewer hot flushes.⁵ If your symptoms are well controlled, we keep the same dose, because the lowest dose that works is the safest.
• After menopause, we use both your blood test and your symptoms. Your ovaries no longer make estrogen, so the level we measure reflects the gel. We aim for the optimal range, and if the level is above our upper limit we lower the dose even if you feel well, because that limit is a safety limit. Symptoms tell us how you feel; the blood test tells us how much estrogen your body really has. We need both, because one alone can mislead us.
• If you still have periods, we use your symptoms. Your ovaries still make estrogen, and the level goes up and down unpredictably, so a single blood test cannot guide the dose.
• The blood test is done the next morning, 9–14 hours after your evening application. In the first hours after applying the gel, the level is much higher, so testing too soon or too late gives a misleading number. If you forgot the gel or applied it at a different time the night before, please tell us and we will move the test to another day, for the same reason.
• Bleeding. If you have any vaginal bleeding, please read the bleeding section on our progesterone page and tell us. Keep using your gel while you wait for any check. If your hot flushes are not severe, we may lower the estrogen, because lower doses mean less bleeding.⁵ Go to a hospital the same day if you have sudden, very heavy bleeding.

• Follow-up visits: every 3 months after you start or change your dose, until things are stable, then every 6 months. Hot flushes take about 12 weeks to improve fully, and the blood level settles within days of a dose change, so a check at 3 months reflects both.^5,2,10
• At every visit we repeat the symptom questionnaire, check your blood pressure, measure estradiol if you are past menopause, ask about bleeding, ask about your breasts and other warning signs, and, if you still have periods, review your contraception.
• Once a year we review with you whether you still benefit and should continue. Guidelines set no fixed time limit, but advise weighing the benefits and risks for each woman regularly.⁵

Estrogen gel and progesterone are not contraceptives.⁵ You can still become pregnant until menopause, and pregnancy at this age carries more risk. If you become pregnant, all our hormones must stop.² We ask every woman who still has periods whether she wants to become pregnant:

• You do not want a pregnancy: we advise contraception until age 55, when pregnancy becomes very unlikely.^5,26
• You would like a baby: we do not start, and refer you to a gynaecologist.
• You do not mind either way: we can start once you understand the reasons above, with a pregnancy test before starting and whenever a period is missed or your bleeding changes.

Methods we suggest, in order:

1. A hormonal coil (fitted by a gynaecologist): one device both prevents pregnancy and protects the womb lining, so you do not need progesterone capsules for protection.⁵
2. A contraceptive implant (fitted by a gynaecologist). You still take progesterone every night to protect the womb.⁵
3. The progestin-only pill (POP): no procedure needed, but you still take progesterone every night to protect the womb.⁵
4. A copper coil: no hormones. You still take progesterone every night.⁵
5. Condoms: no hormones and no procedure. You still take progesterone every night.⁵

We do not use the combined pill with our hormones, because it already contains estrogen, and its risk of blood clots rises from about age 40.^26,5

1. Reed BG, Carr BR. The Normal Menstrual Cycle and the Control of Ovulation. In: Feingold KR, et al., editors. Endotext. MDText.com; updated 2018.

2. Package insert (Thailand): estradiol gel 0.06% with metered-dose pump. Besins Manufacturing Belgium; 2021.

3. Roeca C, Al-Safi Z, Santoro N. The Postmenopausal Women. In: Feingold KR, et al., editors. Endotext. MDText.com; updated 2025.

4. The North American Menopause Society. The 2022 hormone therapy position statement of The North American Menopause Society. Menopause. 2022;29(7):767–794.

5. Panay N, Fenton A, Hamoda H, et al. Recommendations and Key Messages on Women’s Midlife Health and Menopause. International Menopause Society; 2026 (summary published in Climacteric, 2025).

6. Collaborative Group on Hormonal Factors in Breast Cancer. Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence. Lancet. 2019;394:1159–1168.

7. Vinogradova Y, Coupland C, Hippisley-Cox J. Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases. BMJ. 2019;364:k4810.

8. Herink MC. Medication Induced Changes in Lipids and Lipoproteins. In: Feingold KR, et al., editors. Endotext. MDText.com; updated 2025.

9. Gleason CE, Dowling NM, Wharton W, et al. Effects of hormone therapy on cognition and mood in recently postmenopausal women: findings from the randomized, controlled KEEPS–Cognitive and Affective Study. PLoS Med. 2015.

10. Chaikittisilpa S, Orprayoon N, Vallibhakara O, et al. Summary of the 2023 Thai Menopause Society Clinical Practice Guideline on Menopausal Hormone Therapy. J Menopausal Med. 2024;30:24–36.

11. Schierbeck LL, Rejnmark L, et al. Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomised trial. BMJ. 2012;345:e6409.

12. Hodis HN, Mack WJ, Henderson VW, et al. Vascular effects of early versus late postmenopausal treatment with estradiol. N Engl J Med. 2016;374(13).

13. Gordon JL, Rubinow DR, Eisenlohr-Moul TA, et al. Efficacy of transdermal estradiol and micronized progesterone in the prevention of depressive symptoms in the menopause transition: a randomized clinical trial. JAMA Psychiatry. 2018;75(2):149–157.

14. US Preventive Services Task Force. Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Persons: clinician summary. November 2022.

15. International Agency for Research on Cancer. Global Cancer Observatory: Cancer Today (GLOBOCAN 2024). World, females, incidence by age.

16. National Cancer Institute, Thailand. Cancer in Thailand Vol. X, 2016–2018. 2021.

17. Pitakkarnkul S, Tangjitgamol S, Sangariyavanich E, et al. The situation of gynecological cancers in Thailand: incidence, histopathology, and survival outcomes from national cancer registry data. J Gynecol Oncol. 2026;37(1):e56.

18. Fournier A, Berrino F, Clavel-Chapelon F. Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study. Breast Cancer Res Treat. 2008;107(1):103–111.

19. Chlebowski RT, Anderson GL, Aragaki AK, et al. Association of menopausal hormone therapy with breast cancer incidence and mortality during long-term follow-up of the Women’s Health Initiative randomized clinical trials. JAMA. 2020;324(4):369–380.

20. Asi N, Mohammed K, Haydour Q, et al. Progesterone vs. synthetic progestins and the risk of breast cancer: a systematic review and meta-analysis. Syst Rev. 2016;5:121.

21. Royal College of Obstetricians and Gynaecologists, British Society for Gynaecological Endoscopy. Management of Endometrial Hyperplasia. Green-top Guideline No. 67. 2016.

22. British Menopause Society. Management of unscheduled bleeding on hormone replacement therapy (HRT). BMS Guideline. 2026.

23. Maybin JA, Critchley HOD. Menstrual physiology: implications for endometrial pathology and beyond. Hum Reprod Update. 2015;21(6):748–761.

24. Stute P, Neulen J, Wildt L. The impact of micronized progesterone on the endometrium: a systematic review. Climacteric. 2016;19(4):316–328.

25. Fournier A, Dossus L, Mesrine S, et al. Risks of endometrial cancer associated with different hormone replacement therapies in the E3N cohort, 1992–2008. Am J Epidemiol. 2014;180(5):508–517.

26. Faculty of Sexual and Reproductive Healthcare. Contraception for Women Aged Over 40 Years. 2017, amended May 2025.