Premature ovarian failure (primary ovarian insufficiency): Diagnosis, causes, and fertility options for menopause before age 40

The term "premature ovarian failure" is commonly used in Hong Kong, but it is no longer the officially used term in the international medical community. The 2024 updated international guidelines, as well as recent research literature, have adopted the new term.Primary ovarian insufficiency(Premature Ovarian Insufficiency, or POI for short). The name change is not a word game—it reflects an important fact:Ovarian function declines gradually, rather than stopping abruptly.Some patients may still ovulate intermittently after diagnosis, and still have a chance to conceive naturally.

This article begins with a 2019 obstetrics and gynecology interview conducted at Hong Kong Sanatorium & Hospital, supplementing it with current diagnostic criteria, five types of causes, long-term risks to the skeletal and cardiovascular systems, and the most frequently asked questions:What other options are there for getting pregnant?The content accessed in the original text is largely consistent with the current guidelines, but there are several updates to the diagnostic details in 2024, which will be marked one by one in this article.

First, here are the answers: five key points

If you only have two minutes, here are the five things you absolutely need to take with you from this article:

1. Diagnosis is not just about "the age at which menstruation stopped".To be diagnosed, the following three criteria must be met simultaneously: under 40 years of age, menstrual irregularities or cessation of menstruation for at least 4 months, and blood FSH level higher than 25 IU/L. All three are required; irregular menstruation alone is insufficient for a diagnosis.
2. AMH is not a diagnostic tool.AMH reflects ovarian reserve and can be used as an adjunct therapy; however, current guidelines clearly state...Not recommendedAMH is now used as the primary diagnostic test for Point of Interest (POI). This is the biggest difference from the previous draft.
3. The goal of hormone therapy is not just to "feel more comfortable".The guidelines list it asPrimary prevention—It is used to reduce the long-term risk of osteoporosis and cardiovascular disease, and is recommended even if there are no obvious symptoms.
4. Getting pregnant isn't entirely hopeless.The chances of natural pregnancy are approximately 5–10%; egg donation is an established option and a route with a relatively high success rate.
5. The claim of "youthfulness" does not hold true based on the data.Although the prevalence rate has been rising over the past 20 years, it has not reached statistical significance; the increase in cases is largely due to women delaying childbirth and the widespread availability of checkups.

II. Name Update: From "Premature Ovarian Failure" to "Primary Ovarian Insufficiency"

The former term "premature ovarian failure" was translated into English as Premature Ovarian Failure (POF). International guidelines gradually phased out this term after 2015, replacing it with Premature Ovarian Insufficiency (POI), which is often translated into Chinese as...Primary ovarian insufficiency或Premature ovarian insufficiency。

The reason for the name change was clinical observation:"Exhaustion" implies that the function has reached zero, but this is not actually the case.In most patients, ovarian function degenerates gradually, rather than being completely lost all at once. The guidelines clearly state that patients with POI (Posterior Ovarian Inflammation) due to non-surgical causes may still experience intermittent ovarian activity, thus still having a chance of natural conception—therefore, the guidelines also remind patients that:Even if you don't plan to get pregnant, you still need to use contraception.。

Old name	Current name	What's the difference?
Premature ovarian failure (POF)	Primary ovarian insufficiency (POI)	"Exhaustion" implies complete cessation; "functional insufficiency" accurately reflects functional decline but may still indicate intermittent activity.
Premature menopause	Early menopause (40– 44 years old) / POI (before age 40)	Menopause at age 44 (40–44) falls into a different group in the guidelines, and the treatment principles are similar but not equivalent to POI.

In everyday conversation, it's fine to continue using the term "premature ovarian failure," and it's also the most common term when searching online. However, when seeing a doctor or reviewing reports, recognizing the name POI (Premature Ovarian Injury) will be much more convenient.

III. Diagnostic Criteria: Three conditions are indispensable.

Many people believe that "menopause before age 40" is premature ovarian failure, but this is only partly true. Current guidelines require all three criteria to be met for diagnosis.

condition	Specific standards	Common Misconceptions
age	Before 40 years old	40–44 years old menopause is considered "early-onset menopause," not a point of interest (POI).
Menstrual status	Menstrual irregularities or amenorrheaAt least 4 months	One or two late arrivals are not enough to establish [the issue].
Hormones	FSH Above 25 IU/L	It's not true that "not having menstruation means high FSH."

3.1 Three updates to the 2024 guidance

A 2019 visit to Hong Kong Sanatorium & Hospital mentioned "determining through blood tests, ovarian examinations, and hormone levels," which is the correct direction. The international guidelines updated in 2024 have three details worth noting:

1. An elevated FSH level is sufficient for diagnosis with just one test.The 2015 version required two tests, with an interval of at least four weeks; the 2024 version changed this.once FSH levels above 25 IU/L are sufficient, only when...Diagnosis uncertainIt is recommended to retest 6 weeks after 4–. FSH testing does not need to be limited to a specific day of the menstrual cycle.
2. AMH should not be used as a primary diagnostic test.The guidance states this as a "strong recommendation." A low AMH level can further confirm this, but...It cannot be used alone to diagnose POIIt is also not recommended to routinely use AMH to "predict" who will develop POI.
3. Estradiol (E2) is not recommended as a diagnostic criterion.Low estradiol levels only reflect estrogen deficiency and can serve as supplementary evidence, but are not a diagnostic criterion.

3.2 The Role of Ovarian Ultrasound in the Baseline Follicle Count

An ultrasound performed on day 2 to 3 of the menstrual cycle can count the antral follicle count (AFC) in the ovaries. This number also has age-related reference levels; a significantly low number indicates declining ovarian reserve. Like AMH, it belongs to...Auxiliary assessmentIt can provide reference and help in making a judgment, but the guidelines do not list it as a diagnostic criterion for POI.

3.3 After a confirmed diagnosis, these tests are still required.

This part is something that most older drafts completely omitted. Diagnosing a point of injury (POI) is not the end goal; rather, it's about identifying the cause and assessing the organs already affected.

examine	Purpose	Who needs to do it?
Chromosome karyotype analysis	Identify chromosomal abnormalities such as Turner syndrome	All non-medical POIs
FMR1 pre-mutation detection	The POI associated with the Fragile X gene is related to family inheritance.	All non-medical POIs
21-hydroxylase autoantibody	Screening for autoimmune adrenal insufficiency	Unknown cause
Thyroid function (TSH)	Thyroid diseases often coexist with POI.	Upon diagnosis, follow-up testing should be conducted every 5 years or whenever symptoms reappear.
Bone mineral density (DXA)	Assessing the degree of bone loss as a treatment benchmark	All patients at the time of diagnosis

in FMR1 premutationIt should be specifically noted that the guidelines emphasize that it must be...Specialized testing— Conventional multi-gene panel or next-generation sequencingUndetectableIt is important because the results not only affect the patient, but also the risk to other women in the family (sisters, daughters), as well as familial genetic issues related to Fragile X.

IV. Causes: Five categories, two of which require special examination.

The causes of POIs are highly heterogeneous, and the guidelines classify them into the following categories:

category	illustrate	example
Chromosomal abnormalities	X chromosome number or structural abnormalities	Turner syndrome
Genetic factors	Single-gene or oligogene variants	FMR1 premutation, other POI-related genes
autoimmune	The immune system attacks the ovaries or related endocrine glands.	Thyroid disease, adrenal insufficiency
Iatrogenic	Damage to the ovaries during treatment of other diseases	Chemotherapy, radiation therapy, ovarian surgery
idiopathic	The current investigation has not yielded a clear cause.	It accounts for a considerable proportion in clinical practice.

4.1 Iatrogenic POI: One thing you can do before treatment

Positive oophorectomy (POI) can occur due to chemotherapy, radiation therapy, or bilateral oophorectomy required for cancer or other diseases. This type is characterized by...The timing is predictable.In other words, there is an opportunity to address fertility issues before treatment begins.

The guidelines suggest that patients at high risk of iatrogenic points of injury (POIs) may consider [treatment options] before treatment.Fertility preservation(For example, egg or embryo freezing). This has a time limit: once chemotherapy begins, the number of eggs may already be affected, and it may not be possible to preserve them later. If you are undergoing this type of treatment and still plan to have children in the future,You should proactively inform the oncology and reproductive medicine departments before receiving treatment.。

4.2 Genetic factors and family risk

The guidelines explicitly state that sisters and daughters of women with POI (Possibly POI) are at higher risk than the general population. If there is a family history of early menopause or a family history of fragility X-related learning disabilities, it is advisable to proactively inform your doctor during your consultation. This is not meant to cause anxiety, but rather to encourage...Family members can have the check-up done at an appropriate time.The sooner you know, the more choices you'll have.

V. Effects on the body: Not just fertility

Decreased ovarian function directly results in chronically low estrogen levels. The effects of estrogen extend far beyond menstruation and fertility, also affecting the skeletal, cardiovascular, and genitourinary systems.

5.1 Skeleton: The most far-reaching influence

Low estrogen levels can accelerate bone loss. POIs are characterized by...Bone degeneration begins more than ten years earlier than in the general population.Therefore, osteoporosis may become more severe in old age—this is precisely the "longest-term impact" emphasized by Dr. Tang Oi-shan during an interview at Hong Kong Sanatorium & Hospital.

The guidelines therefore recommendA bone mineral density (DXA) test should be performed at the time of diagnosis.It's important to start treatment now, rather than waiting until symptoms appear or you're older. Having baseline values allows you to determine if treatment is effective and if adjustments are needed. Daily calcium and vitamin D intake, along with weight-bearing exercise, are fundamental for bone health; this section can be found in [reference needed].Dietary strategies for menopausal bone loss與Prevention and treatment of osteoporosis。

5.2 Cardiovascular health: A topic almost entirely omitted from previous drafts.

A meta-analysis encompassing 16 studies, 40,549 women with point of injury (POI), and 1,016,633 controls showed that even after adjusting for the effects of hormone therapy, the incidence of POI was significantly lower in women with POI.The combined risk of cardiovascular events remains approximately 351 TP4T higher.(Adjusted HR 1.35, 95% CI 1.06– 1.63).The risk of coronary heart disease is about 421 TP4T higher.(HR 1.42, 95% CI 1.17– 1.66); no significant difference was observed in the risk of stroke and cardiovascular death.

This number should not be interpreted as "definitely having heart disease," but rather as indicating:Points of interest (POIs) are risk factors for cardiovascular disease.The practical significance is that things like blood pressure, blood lipids, blood sugar, smoking, and weight, which are already things to be careful about, deserve even more serious attention in POI patients and should be monitored regularly.

5.3 Symptoms and Quality of Life

The symptoms of estrogen deficiency are similar in nature to those of natural menopause, only they occur earlier:

• Vasomotor symptomsHot flashes, night sweats, palpitations, dizziness
• Urogenital systemSymptoms include vaginal dryness, painful intercourse, and recurrent urethral or vaginal infections.
• Sleep and MoodSymptoms include insomnia, fatigue, irritability, mood swings, difficulty concentrating, and memory loss.

These symptoms are manageable and do not need to be endured silently. On the other hand, the Hong Kong Department of Health also reminds the public:If any vaginal bleeding occurs after menopause, seek medical attention immediately.This is a signal that other problems need to be ruled out.

6. Hormone therapy: It's not something you only take when you have symptoms.

This is the section where the old draft differs most from the current guidelines, and it is also the section most likely to affect long-term health.

6.1 Why do the guidelines recommend using it "even if there are no symptoms"?

The 2019 survey described hormone therapy as "relieving discomfort symptoms," but that's only half the story. Current guidelines list it as...Primary prevention measures—Its function is to reduce the symptoms of POI caused by long-term estrogen deficiency in patients.Osteoporosis, cardiovascular disease and premature deathThe risk,It is recommended to use regardless of whether symptoms are present.。

In other words, the severity of hot flashes is not the key factor in deciding whether or not medication is needed.The very fact that one lacks estrogen is a reason to need medication.

6.2 For women with an intact uterus, progesterone must be used simultaneously.

The old draft only mentioned "estrogen supplementation," and this needs to be corrected. The guidelines clearly require:For women who still have a uterus, estrogen combined with progesterone must be used.This is to protect the endometrium and prevent endometrial hyperplasia and cancer. Estrogen alone is only suitable for patients who have had their hysterectomy.

In addition, when the estrogen dose is high, the progesterone dose should also be increased accordingly.

6.3 Dosage and route of administration

The guidelines provide a reference dose for the goal of "protecting bone health" as follows: dailyOral administration of estradiol not less than 2 mg,orTransdermal estradiol 100 microgramsOr an equivalent dose. The specific type and dosage to be used will be determined by the doctor based on the individual case.

The choice of approach is meaningful: for example, there aremigraine with auraFor individuals with bone loss, the guidelines recommend transdermal estrogen therapy, as this may be a lower-risk route. For those using combined oral contraceptives, continuous or extended regimens are recommended to reduce bone loss.

6.4 How to understand breast cancer risk

The previous article mentioned that "long-term use of excessive estrogen may increase the risk of breast cancer." This statement...Typical menopausal groupsThe discussion had its context, but it's not appropriate to apply it to POI patients. The current guidelines state: [The text abruptly ends here, likely due to an incomplete sentence or missing information.]Compared to women of the same age without point of interest (POI), there is no evidence that hormone therapy increases the risk of breast cancer.。

The difference lies in the following: discussions about breast cancer risk during menopause generally come from studies of older women using hormone therapy; while POI patients are those who have recovered through medication.It should have beenHormone levels vary. Of course, guidelines generally do not recommend hormone therapy if there is a history of breast cancer—this must be evaluated by a doctor.

6.5 Until what age will it be used?

A 2019 survey suggested that medication should be taken no later than age 50, roughly the same age as menopause. Current guidelines state:Continue use until the normal age of menopause.(The median age of menopause for women in Hong Kong is 51.) After reaching that age, individuals should assess whether to continue menstruating based on their individual risk and benefit profiles.

Both approaches are consistent, the difference being that "50 years old" is an approximate integer, while the guidelines use the "typical natural age of menopause." For women who didn't menopause until age 44 (40–), this is incorrect.Premature amenorrheaThe principles are similar across different ethnic groups – the UK's NHS also recommends hormone supplementation for women who have gone through menopause before age 45, as they are at higher risk of bone and heart problems.

VII. Wanting to get pregnant: What other options are available?

This is the part that gets searched the most, and is also the easiest to dismiss with a simple "there's no way to recover it" from old drafts. The truth is:Restoring the original ovarian function is indeed impossible, but getting pregnant does not mean there is no hope at all.The following are arranged from nearest to farthest in terms of actual situation.

7.1 Natural pregnancy: Approximately 51 TP1T101 TP4T

A literature review indicates that the natural pregnancy rate for women in POIs is approximately [missing information]. 5–10%The guidelines also explicitly require that women undergoing non-surgical point-of-injection (POI) should be informed.Ovarian activity may occurAnd with the chance of natural conception.

This point has two practical implications. First,Don't completely give up the possibility of natural pregnancy just because you have a confirmed diagnosis.Secondly, conversely,If you don't plan to get pregnant, you should use contraception.This is precisely the aspect that the guidelines emphasize at the same time.

As for "whether there are ways to increase the chances of natural pregnancy", the guidelines provide a fairly clear answer:Currently, no intervention has been reliably proven to increase ovarian activity or natural conception rates.This item has the highest level of evidence in the entire guideline, meaning that existing research is quite consistent, not that "there is no research yet." This is worth keeping in mind if someone tries to sell you treatments or supplements that can "activate the ovaries."

The good news is: women with idiopathic POI, or most cases following chemotherapy POI, who are able to conceive naturally, have a higher chance of recovery.Obstetric and neonatal risks are not higher than in the general population.。

7.2 Egg donation: An established option

The guidelinesEgg donationListed as a POI after diagnosisEstablishedThis is a route to pregnancy that was not mentioned at all in the previous article, and it is also the most practical option for patients with "severely declining ovarian function"—because it does not require the patient's own eggs.

It needs to be stated truthfully that: pregnancy through egg donation is a [missing information - likely related to pregnancy].High-risk pregnancyThe pregnancy should be managed by an obstetric unit with the appropriate qualifications, and the donor should proactively inform the obstetric team of the source of the pregnancy. If the eggs are donated by a sister, although they are genetically similar, there is a shared genetic risk, and the ovarian stimulation cycle cancellation rate of the egg donor is relatively high. These factors need to be fully discussed before making a decision.

In Hong Kong, egg donation is regulated by the Human Reproductive Technology Ordinance (Chapter 561).The commercial sale of gametes is illegal.Actual arrangements require assessment and processing by a licensed center. Those interested should contact a reproductive medicine specialist or licensed center directly, and should not attempt to process matters online.

7.3 Using one's own eggs for in vitro fertilization

The 2019 interview mentioned that "if the ovaries are only experiencing functional decline but have not yet completely stopped menstruating, artificial ovarian stimulation can still be attempted." This direction still holds true, but the limitations need to be truthfully explained:

• POI patients typically respond well to ovulation-inducing drugs.PoorThe number of eggs that can be obtained is limited;
• Success rate is highly correlated with age, remaining ovarian function, and whether intermittent ovulation still occurs;
• The guidelines indicate that most women with point of infertility (POI) have nearly depleted follicles by the time they are diagnosed, and the chances of obtaining eggs are not high.

Therefore, this approach is worth trying, but it's advisable to discuss it with your doctor at the same time.Egg donationThis option, rather than investing all your time in self-egg treatment, is a good alternative. For patients under 40, time is a significant variable.

7.4 Fertility Preservation: The Time Window is Before Diagnosis

If you are aware that you will be receiving treatments that may damage your ovaries (chemotherapy, radiation therapy, ovarian surgery), and you still plan to have children in the future, you should...Before treatment beginsDiscuss egg or embryo freezing. This is the only step where "doing it earlier gives you more options."

8. Is the "youthfulness" trend real?

There seems to be an increase in individual cases at the outpatient clinic, and this observation deserves serious consideration, but data and feelings should be viewed separately.

During her 2019 visit, Dr. Deng Aishan's assessment was:Clinical data did not show a significant upward trend.The difference may stem from two aspects—previous generations of women gave birth earlier, making ovarian function problems less likely to be detected; while modern women marry and have children later, and with the widespread availability of checkups, they are often diagnosed at a younger age.

This assessment largely aligns with subsequent data. A global meta-analysis shows that the overall prevalence of POIs is approximately... 3.5%Trends over the past 20 yearsAlthough there has been an increase, it has not reached statistical significance.(p > 0.05). In other words:A significant portion of the increase in cases can be explained by the increase in examinations.

As for the prevalence figures themselves, there are significant differences between different sources: textbooks used to cite "approximately 11 TP4T before age 40 and approximately 0.11 TP4T before age 30," while the global aggregate analysis in 2023 and the guidelines for 2024 both use... 3.5%This discrepancy primarily stems from differences in diagnostic criteria and the study population, and should not be directly interpreted as "the incidence rate has tripled." A more prudent interpretation would be:POIs are more common than previously thought.However, there is no reliable evidence that it is rapidly becoming younger.

IX. Things you can do on a daily basis

Medication treatment is determined by a doctor, but the following are aspects that you can manage yourself:

direction	Specific practices	Why it is important
Calcium	Adults take 800 mg of TP1T1000 mg daily; those 50 years of age or older take 800 mg of TP1T1300 mg daily (total intake from food and supplements should not exceed 2000 mg).	Bone loss begins earlier, making calcium needs even more important.
Vitamin D	Expose your face and arms to gentle sunlight for about 10 minutes daily; those with limited sun exposure should supplement with medications as advised by their healthcare provider.	Helps with calcium absorption
Weightlifting	brisk walking, jogging, dancing, Tai Chi, badminton	Stimulates bones while protecting the cardiovascular system
Quitting smoking and limiting alcohol consumption	Quit smoking completely; avoid excessive alcohol consumption.	Both are factors contributing to bone loss and cardiovascular risk.
Cardiovascular indicators	Regularly measure blood pressure, blood lipids, and blood sugar.	POIs are cardiovascular risk factors and should be assessed at baseline as early as possible.
Sleep and Mood	Get enough sleep and relaxation exercises; if you experience persistent low mood, seek help proactively.	Sleep and mood symptoms are common and manageable.

aboutNutritional supplementsThe positioning needs to be clearly explained:Currently, no supplements have been proven to restore ovarian function or increase the natural conception rate in patients with POI.The evidence level for this item is at the highest level. The appropriate role of supplements is...Bone protectionThis step—when dietary intake is insufficient, calcium and vitamin D can fill the gap—should be assessed by a doctor or nutritionist based on actual intake, rather than being treated as ovarian maintenance products. Any product claiming to "activate the ovaries" or "restore ovarian function" should be treated with caution.

Additionally, if you also experience menstrual pain or other menstrual discomfort, you can refer to...Traditional Chinese Medicine Constitution and Dietary Therapy for Menstrual PainHowever, this is a different matter from POI processing and should not be confused.

10. When to request medical attention

When seeking medical attention, it is recommended to bring your menstrual records (cycle length and flow changes over the past six months), a list of medications and supplements you are currently taking, and your family medical history. This information is more helpful in determining whether you need treatment than a single blood test.

XI. Frequently Asked Questions

Does premature ovarian failure equal menopause?

Not entirely equivalent. Both involve similar hormonal changes, with both showing low estrogen levels; the difference lies in...Age of occurrence與Follow-up processingNatural menopause typically occurs between the ages of 45 and 55 and is a natural physiological process; POI, on the other hand, occurs before the age of 40, requiring identification of the cause, and because of the longer duration of estrogen deficiency, the risk to bones and the cardiovascular system is also higher. Therefore, hormone therapy for POI is recommended to continue until the normal age of natural menopause, rather than "only using it when symptoms appear."

Does menopause before age 40 always mean premature ovarian failure?

Not necessarily. A diagnosis requires three conditions to be met simultaneously: under 40 years of age, irregular menstruation or amenorrhea for at least 4 months, and FSH levels above 25 IU/L. In addition, pregnancy, thyroid disease, high prolactin levels, and the effects of birth control pills or other hormonal medications must be ruled out—all of which can cause amenorrhea or changes in FSH levels. Therefore, a conclusion cannot be drawn solely based on age and menstrual history; a doctor must perform blood tests to determine the cause.

Does a low AMH level indicate premature ovarian failure?

No. AMH reflects the number of follicles in the ovaries, also known as "ovarian reserve," which declines naturally with age and is also affected by factors such as birth control pills and recent ovarian surgery. Current international guidelines clearly state...Not recommendedWhile AMH is considered the primary diagnostic test for POI, it is not recommended for predicting who will develop POI. A low AMH level can be suggestive, but a definitive diagnosis requires considering menstrual history and FSH levels, and ruling out other causes. A single low AMH level does not equate to a confirmed diagnosis.

Can premature ovarian failure be reversed?

Based on current medical evidence,Lost ovarian function and egg count cannot be restored.The guidelines state that no intervention has been reliably proven to increase ovarian activity or natural conception rates, a conclusion with the highest level of evidence. However, "irreversible" does not mean "nothing can be done": hormone therapy can protect bones and the cardiovascular system, egg donation can provide a pathway to pregnancy, and the chance of natural conception still exists (approximately 5–10%). The focus should be on allocating resources to these evidence-based approaches.

Do I need to take hormones if I don't want to have children?

Yes, it is necessary, and this is often misunderstood. Guidelines recommend hormone therapy for patients with point of injury (POI).Until the normal age of menopauseAsPrimary preventionIt is used to reduce the risk of osteoporosis, cardiovascular disease, and premature death.Regardless of whether there are symptomsIn other words, the decision to use medication is not based on the severity of hot flashes, but on the fact that the body has a long-term lack of estrogen. The actual treatment plan and dosage must still be determined by the doctor based on the individual's circumstances (including whether the uterus should be preserved, whether there is a history of migraines, breast cancer, etc.).

Does hormone therapy increase the risk of breast cancer?

Regarding the POI (Point of Interest) group, the current guidelines state: compared to women of the same age without POI,There is no evidence that hormone therapy increases the risk of breast cancer.This differs from the typical discussion of menopause—where data primarily comes from older women—while POI patients are using medication to restore their pre-existing hormone levels. However, guidelines generally do not recommend its use if there is a history of breast cancer; this must be assessed by a doctor. Any concerns should be discussed with your doctor before prescribing.

Is it still possible to conceive naturally if you have premature ovarian failure?

Yes, the chance is approximately 5–10%. Guidelines require explaining to patients with non-surgical POI that ovarian activity may still occur intermittently, therefore the chance of natural conception exists. And because of this,Even if you don't plan to get pregnant, you still need to use contraception.—This is the other side of the same coin. As for whether medication or treatment can improve this chance, there is currently no reliable evidence to support this.

Is egg donation possible in Hong Kong?

Yes, but it is regulated by law. Egg donation in Hong Kong is regulated by the Human Reproductive Technology Ordinance (Chapter 561).The commercial sale of gametes is illegal.Egg donation is voluntary, and actual arrangements must be assessed and processed by a licensed center. International guidelines list egg donation as a confirmed route of pregnancy after a point of interest (POI) diagnosis, but also point out that pregnancy with donated eggs carries a higher risk and requires follow-up by a qualified obstetric unit. Those interested should contact a reproductive medicine specialist or licensed center directly.

If there is a family history of the disease, can I get tested earlier?

Yes, and it's worthwhile. The guidelines indicate that sisters and daughters of women with POI (Position of Interest) are at higher risk and recommend informing them of related symptoms and encouraging them to seek medical attention promptly. If there is a family history of early menopause or a family history of Fragile X-related learning disabilities, this should be proactively mentioned to the doctor during consultation—this may affect whether FMR1 premutation testing is necessary. It's important to note that FMR1 premutation testing is mandatory.Specialized testingConventional multi-gene panels cannot detect it.

Is a menstrual cycle of 21 or 40 days considered abnormal?

A duration of 21 to 35 days is within the normal range, so 21 days and 35 days are not abnormal in themselves. What is truly worth noting is...changeIf your cycle has always been regular, but suddenly shortens to less than 21 days, lengthens to more than 35 days, or doesn't occur for several months, you should get checked. The old article stated that "normal women ovulate approximately every 28 to 30 days," but this range is too narrow and can easily mislead people with cycles of 32 or 33 days into thinking there's a problem.

XII. Sources of Information

• European Society of Human Reproduction and Embryology (ESHRE), etc., "Evidence-based guideline: premature ovarian insufficiency",Human Reproduction Open, 2024.PubMed 39660328｜PMC Full Text
• 〈The global prevalence of premature ovarian insufficiency: a systematic review and meta-analysis〉,Climacteric, 2023.PubMed 36519275
• "Cardiovascular Events Among Women with Premature Ovarian Insufficiency: A Systematic Review and Meta-Analysis",Reviews in Cardiovascular Medicine, 2023.PubMed 39077000
• 〈Pregnancy outcome in patients with idiopathic premature ovarian insufficiency: a systematic review of the literature〉,Reproductive BioMedicine Online, 2026.PubMed 42025142
• Hong Kong Department of Health Family Health Service, Menopause in Women (FHS-WH26AB).fhs.gov.hk
• Hong Kong Department of Health Family Health Service, Menopause and Hormone Replacement Therapy.fhs.gov.hk
• Hong Kong Department of Health Family Health Service, "Adequate Calcium Intake" (FHS-WH97B).fhs.gov.hk
• UK NHS, <Early or premature menopause> (reviewed in March 2025).nhs.uk
• Hong Kong Human Reproductive Technology Authority.chrt.org.hk| Human Reproductive Technology Regulations (Chapter 561)Electronic version of Hong Kong laws
• Hong Kong Sanatorium & Hospital, "The Forty-Point Limit for Premature Ovarian Failure", Hong Kong Sanatorium & Hospital Health Notebook, March 6, 2019 (Source of this article: Interview with Dr. Tang Oi-shan, Department of Obstetrics and Gynecology, Hong Kong Sanatorium & Hospital).hksh-hospital.com

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