Sep 27

Understanding Premature Ovarian Insufficiency: Everything You Need To Know

In this guide you will learn about premature ovarian insufficiency: including the symptoms, how it is diagnosed, fertility impacts and treatment options. Get the support and knowledge you need.

What is POI or Premature Ovarian Insufficiency?

Ovarian function persists for most women into the 40s, with menopause or the end of hormonal menstrual cycles typically occurring between ages 45 to 55. It is a transition every woman experiences as a part of aging.

Premature Ovarian Insufficiency: when the ovaries stop functioning as expected before age 40.

Early Menopause: when the ovaries stop functioning as expected before age 45.

Premature ovarian insufficiency is the early onset of menopausal symptoms along with decreased ovarian hormone production (estrogens - especially estradiol, progesterone, testosterone, and AMH), reduced ovarian follicles, reduced ovulation and reduced fertility.

Understanding POI is crucial, as it not only influences reproductive health but also has long term health impacts such as increased lifetime risk of osteoporotic fractures, frailty and cardiovascular and degenerative brain disorders that can impact physical and emotional wellbeing (Neuro Disease and POI 2018).

The decrease in estrogen production can cause many varied menopausal symptoms, such as fatigue, insomnia, mood changes, exaggerated premenstrual symptoms, headaches, hot flashes and night sweats.

Because POI occurs before the typical age and the symptoms can be varied across multiple systems of the body, there is often a delay to diagnosis.

Premature ovarian insufficiency is a more accurate term than primary ovarian failure as the condition is a process of decline in ovarian function with some low level residual or intermittent ovarian function.

young women smiling despite premature ovarian insufficiency.

How Common is Premature Ovarian Insufficiency?

POI is typically thought to affect 1 in every 100 women before age 40.

It affects 1 in every 1000 women before age 30.

However, it is important to note that this number can vary greatly depending on factors such as ethnicity and underlying medical conditions.

A recent global meta-analysis suggests the prevalence is even higher, impacting around 3.1 percent of women in developed countries and 5.4% of women in developing countries (Global Prevalence of Premature Ovarian Insufficiency 2023).

What Are The Symptoms of Premature Ovarian Insufficiency?

The symptoms of POI can vary from person to person, but common symptoms include:

Irregular or absent periods
New premenstrual symptoms or exaggerated PMS
Fatigue
Sleep disturbances
Joint pain, joint stiffness and muscle aches
Vaginal dryness,
Itchy skin or dry skin,
Decreased sex drive
Mood changes, including depression and anxiety
Poor concentration, memory disturbance or brain fog
Hot flashes and night sweats
Difficulty conceiving

It is important to note that these symptoms are not exclusive to POI, and can also be attributed to other medical conditions.

What Causes Premature Ovarian Insufficiency?

For the majority of women, the cause of spontaneous premature ovarian failure is unknown. This is known as idiopathic POI and affects 70–90% of women with POI.

Iatrogenic POI is when premature ovarian insufficiency is caused by medical treatment. This can include: chemotherapy or radiation therapy, medications, ovarian surgery or other pelvic surgery that causes a reduction in ovarian function resulting in POI.

Other causes may include:

Gene/Chromosomal-related conditions (e.g. Turner syndrome, Fragile X syndrome). 30 percent of women with idiopathic POI do have a family history of POI and this suggests a genetic component, even if the specific genes are not known.
Autoimmune disorders such as: Hashimotos thyroid disease, type I diabetes, adrenal insufficiency, Sjögren’s syndrome, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, coeliac disease, myasthenia gravis and autoimmune alopecia.
Infection or inflammation of the ovaries
Chemical toxin exposures: polycyclic aromatic hydrocarbon found in cigarette smoke, phthalates and bisphenol-A found in plastic production and other environmental pollutants are also possible causes.

Risk Factors for Premature Ovarian Insufficiency

One of the significant risk factors for premature ovarian insufficiency is a family history of the condition. There are some modifiable risk factors that include:

Gynaecological surgeries such as ovary removal (oophorectomy), partial ovarian tissue removal, hysterectomy,
Lifestyle factors – smoking
Modified treatment regimens to reduce ovarian damage for cancerous and chronic diseases.

How is Premature Ovarian Insufficiency Diagnosed?

Diagnosing POI can be challenging, in the early stages, before the periods become irregular, there may be a cluster of seemingly unrelated symptoms.

Once there are changes to the periods, the 2 criteria for diagnosis include:

Irregular or absent periods (meaning the menstrual cycle lasts for more than 35 days for at least 4 months)
Elevated FSH hormone (follicle stimulating hormone) made by the pituitary gland in the brain. It has to be elevated on 2 occasions and at least 4 weeks apart.

Premature ovarian insufficiency is diagnosed when a woman has irregular periods or no periods for 4 months before 40 years of age alongside blood tests that show a high follicle-stimulating hormone (FSH). Different clinical groups have different diagnostic criteria.

The most widely utilized diagnostic limit is > 40 IU/l,
National Institutes for Health and Care Excellence Guideline suggests FSH > 30 IU/l 47,
European Society of Human Reproduction and Embryology (ESHRE) Guideline suggests FSH > 25 IU/l.

To confirm the diagnosis these tests should be repeated after 4-6 weeks so see if they are consistently elevated. Where periods are still occuring, testing should be done on day 2-3 of the menstrual cycle (ie 2nd or 3rd day of the period).

Your health provider may also perform other tests such as:

A pregnancy test: to exclude pregnancy
Anti-Mullerian Hormone (AMH) test: AMH is a hormone produced by small follicles in the ovary. As POI decreases ovarian reserve, blood levels of AMH are often lower than typical for a person's age.
Testosterone: to exclude polycystic ovary syndrome (PCOS) as this causes irregular or missed periods.
Blood tests such as thyroid hormones, adrenal hormones, coeliac antibodies to check for causes of POI.
Further testing such as genetic testing and auto-antibody testing to determine cause of POI
Testing for markers of metabolic health such as HBA1C and lipids,
DEXA bone scan to check bone density.

Pregnancy and Premature Ovarian Failure

Some women with POI have intermittent ovarian function - particularly those with idiopathic POI. Around 25 percent may ovulate, but only 5-10 percent will be able to conceive (POI & Fertility 2019).

Many women who are seen in fertility clinics have decreased ovarian reserve.

IVF and Premature Ovarian Failure

Women with POI often require higher doses of IVF medications to stimulate follicle development. IVF can be a stressful road as the response to ovarian stimulation is often poor, with four or fewer follicles available for retrieval. This means few or no embryos are available for transfer or cryopreservation.

Women with POI may require multiple consecutive IVF cycles to achieve successful embryo implantation.

Egg or embryo donation has high success rates, 50-60 percent of women with POI who have a donor egg or embryo have a successful pregnancy and live birth (POI & Fertility 2019).

Can I Reverse Premature Ovarian Failure?

Animal models are used to establish pathways that can be optimised to delay follicle decline in premature ovarian insufficiency. It is well accepted that melatonin levels fall before FSH levels rise in premature ovarian failure.

Melatonin and resveratrol are both powerful antioxidants and they act together on SIRT1/FOXO3a/BCL2 pathways. In animal models they slow the decline in follicle reserve and decrease DNA breaks.

There is a case study of a 39 year old published in 2023 of a women who was treated using physiological hormone replacement with estradiol and cyclical micronised progesterone.

They also used melatonin resveratrol. After 3 months she had ovarian hormone levels in the physiological range and 5 months later conceived (Melatonin and Reveratrol for POI 2023).

Studies of ovarian insufficiency in mice have shown the benefits of vitamin D supplements for fertility due to their antioxidant effect (Nasri K et al, 2019). Women with POI often have low levels of vitamin D. Vitamin D supplementation may also help reduce FSH serum levels (Low VitD & POI 2020).

Supplements To Support Conception with Premature Ovarian Failure

These studies suggest the following 3 treatments could be used to support hormone cycles in women with premature ovarian insufficiency.

Physiologic hormone therapy with estradiol and micronised progesterone
High dose melatonin and resveratrol important antioxidants
Vitamin D supplementation

premature ovarian insufficiency supplements: resveratrol and melatonin and vitamin D.

Fertility Preservation

For women diagnosed with medical conditions or who are undergoing medical treatments that may cause POI, fertility preservation may be important.

Techniques such as egg freezing before treatment or exploring assisted reproductive technologies (ART) may be available. Consulting with fertility specialists early can open doors to potential solutions.

Contraception and Premature Ovarian Insufficiency

If you do not wish to become pregnant, it is advisable to continue to use contraception if you are in a heterosexual relationship until you have experienced menopause.

Treatment Options for Premature Ovarian Insufficiency

There are important treatment options available to help manage symptoms, improve quality of life and prevent development of premature chronic health conditions such as heart disease, diabetes and osteoporosis.

HORMONE REPLACEMENT THERAPY (HRT)

HRT can help alleviate menopausal symptoms such as hot flashes, vaginal dryness and sleep disturbances. It is also important for maintaining heart health, metabolic health, bone health and reducing the risk of osteoporosis.

The aim of hormone therapy in POI is to achieve estrogen levels in the physiological range to at least the age of typical menopause.

The estrogen therapy options are:

oral estradiol 1–2 mg daily (body identical) or
oral conjugated equine estrogens 0.625–1.25 mg daily or
transdermal estrogen patch or gels 0.1 mg daily (body identical) (Ratner and Ofri, 2001).

Progestogens are always added alongside estrogen if you have a uterus to protect the endometrium. This can be continuously given (daily), but if aiming for pregnancy, it is given cyclically, for example:

micronized progesterone 200 mg (body identical) daily for 12-14 days per 28 days or
medroxyprogesterone acetate 10 mg daily for 12–14 days per 28 days (Crofton et al., 2010).

COGNITIVE AND PSYCHOLOGICAL SUPPORT

The impact of POI on fertility and overall health can take a toll on one’s mental well-being. The diagnosis can result in experiencing many emotions and grief. It can be challenging to come to terms with learning about their condition, long-term health consequences, difficulties with conceiving and the impacts on these on self-esteem, self-compassion and body-image.

Support is needed for women as they navigate the emotional challenges regarding the hormonal changes their body is experiencing.

Additionally there is evidence that both bilateral oophorectomy (Depression & Anxiety after Oophorectomy 2008) and conservative hysterectomy - where the ovaries remain in the body but the uterus is removed, (Mental Health After Hysterectomy with Ovary Conservation 2020) are both associated with an increased risk of new onset long-term depression and anxiety that is thought to be hormonally mediated depression and anxiety due to loss of ovarian hormones.

Where loss of ovarian hormone contriutes to mood symptoms, the treatment of plan should consider replacing estradiol and or testosterone to reduce symptoms of deficiency.

Loss of ovarian hormones can also have significant cognitive effects such as brain fog, poor concentration, insomnia, which can have impacts on self-esteem, wellbeing, relationships and career. Treatment of cognitive symptoms can be supported with physiologic hormone replacement therapy.

Seeking psychological support through therapy, counselling, CBT or joining support groups can help you navigate the emotional hurdles of living with POI.

SEXUAL WELLBEING

POI impacts on sexual function in a number of ways. Due to hormonal changes women may experience lower sexual desire, and less sexual fantasies. They will often also have phsyical impacts including vaginal dryness, reduced lubrication and discomfort during intercourse.

Vaginal dryness and genitourinary symptoms of menopause can be treated with low dose hormone creams including estrogen cream, testosterone cream or DHEA pessary, a precursor hormone that is converted to estrogen and testosterone in the vaginal tissues.

Where sexual desire/libido is impacted by loss of ovarian hormones, the treatment should consider replacing estradiol and or testosterone to reduce the impact of hormone deficiency on sexual desire (Review POI 2020).

Seek help from a sexual therapist, seek out professional advice or support groups.

CARDIOVASCULAR AND METABOLIC HEALTH

It is well established that untreated POI increases the risk of heart disease and cerebrovascular diseases (diseases of the brain related to blood vessels or blood flow) such as strokes.

Untreated estrogen deficiency in premature ovarian insufficiency contributes to:

deranged lipids,
insulin resistance,
obesity,
inflammation,
high blood pressure
constriction of blood vessels,
loss of nitric oxide production which helps open blood vessels
autonomic nervous system dysfunction, contributing to fluctuating heart rate, abnormal health rhythms, and blood pressure control.

HRT is protective against these changes and women who have the lowest disease risk are those who used HRT the longest, especially for longer than 10 years (Menopause and Heart Disease 2019).

Lifestyle Changes to Manage Premature Ovarian Insufficiency

While treatment options are important, maintaining a healthy lifestyle is also crucial for managing POI. Making simple lifestyle changes can help alleviate symptoms and improve overall health.

DIET

Eating a balanced diet that includes plenty of fruits, vegetables, whole grains and lean proteins can help manage weight gain associated with POI as well as reduce the risk of developing chronic health conditions.

EXERCISE

Regular exercise is important for general health and wellbeing. It is also important for weight management and improving cardiovascular health.

STRESS MANAGEMENT

Stress can worsen symptoms of POI. Additionally the hormone changes associated with POI can make it more difficult for the body to cope with stressors.

It is important to have a number of strategies that help you to manage stress and down-regulate your nervous-immune-endocrine systems when they are upregulated or overloaded.

Some helpful strategies include:

relaxation techniques such as deep breathing, meditation or yoga.
journalling
down time where you can do pleasurable activities
time outdoors in nature
talking to a trusted friend.

BONE HEALTH

Estrogen deficiency can lead to bone loss and an increased risk for osteoporosis. The following are essential for maintaining strong bones.

Calcium: It is important to get adequate dietary calcium of around 1000 mg daily. This can be found in dairy products, leafy green vegetables and fortified foods like soy milk.

Vitamin K2: is needed for 2 proteins; matrix GLA protein and osteocalcin to function, which help to build one. It is found in green vegetables, egg yolks, liver and some fermented cheese.

Vitamin D: is important for bone health, aim to get 20 minutes of daily sunshine. A small amount of vitamin D can also be found via dietary sources including mushrooms, fatty fish and egg yolks. Consider supplementing vitamin D in winter.

Weight-bearing exercises: such as walking, jogging or weight lifting can also help improve bone density. are also important for maintaining bone health.

woman with premature ovarian insufficiency lifting weights to preserve bone health

SMOKING CESSATION

Smoking is a risk factor for premature ovarian failure. It also increases the risks of chronic diseases that are more common in women with POI such as heart disease and osteoporosis, making it even more crucial for women with POI to quit smoking. Talk to your health provider to get support.

Finding Support

Finding support plays an important role in learning about your condition and from others with similar lived experiences. The following websites provide more information for people with premature ovarian insufficiency.

The Takeaways About Premature Ovarian Insufficiency

Premature Ovarian Insufficiency is a condition that can have significant impacts on fertility, emotional well-being, sexual function and overall health for the rest of your life.

The treatment options can help alleviate symptoms and improve quality of life and reduce long term health risks.

It is important for women with POI to seek support from healthcare professionals and make necessary lifestyle changes to manage the condition effectively. We need to raise awareness about this condition and provide support for women who are living with POI.

So let's spread the word and make sure everyone with POI has access to appropriate treatment options.