Primary ovarian insufficiency (POI) is a condition in which a woman’s ovaries stop functioning properly before 40yo. Although POI can be a challenging diagnosis, it is important to understand that it is not the same as menopause. In this blog post, we will explore the causes, symptoms, and potential management options for POI, as well as offer guidance on managing the emotional and physical aspects of this condition.

What is Primary Ovarian Insufficiency (POI)?

Primary ovarian insufficiency (POI) is when the ovaries stop working before the age of 40yo; this is compared to the average age of menopause, which is approximately 51yo. POI affects approximately 1 in 250 women by the age of 35yo, and 1 in 100 women by the age of 40yo.

By definition, menopause occurs when a woman has experienced 12 months without having a period, without any obvious underlying cause (eg. having a Mirena in place, having had a hysterectomy etc).

Is POI the same as ‘premature menopause’?

Sometimes, the term Primary Ovarian Insufficiency (POI) is confused (or used synonymously) with ‘premature menopause’. But these conditions aren’t the same:

• Women with POI can have irregular or occasional periods for years; they might even fall pregnant
• Women with premature menopause stop having periods, and cannot become pregnant

Causes of POI

In 70% of women with POI, no underlying cause is ever found: this is called ‘idiopathic’ POI. In approximately 30% of women with POI, an underlying genetic predisposition may be discovered; in 10% of women with POI, it runs in the family. These genetic tests are not routinely performed: if you are interested in having these tests performed, please ask your doctor to refer you to a genetic counsellor, such as those at Siles Health.

Some conditions can cause ovarian insufficiency, such as:

• Prior damage to ovarian tissue, which can occur due to ovarian surgery, chemotherapy and / or radiotherapy
• Adrenal insufficiency, which can lead to: weight loss, vague abdominal pain, weakness, fatigue, salt cravings and / or skin pigmentation
• A personal and / or family history of autoimmune conditions, such as: underactive thyroid; Grave’s disease; vitiligo; myasthenia gravis; coeliac disease; and / or type 1 diabetes
• A family history of so-called ‘fragile X syndrome’

Symptoms of POI

The symptoms or POI are similar to those that women normally experience in their mid- to late-forties, who go through menopause at the usual age. These symptoms include:

• Menstrual cycle becoming progressively longer
• Periods stopping all together
• Hot flushes

Periods becoming irregular or ceasing all together

The most common symptom of POI is periods becoming less and less frequent (ie. the number of days between the first day of one period and the first day of the next increasing), until eventually periods stop all together. For some patients, this is a very gradual process, occurring slowly over a year or two; for others, their periods suddenly stop, never to return.

For some women, the first hint that they are going through POI is when their period doesn’t return after they come off the contraceptive Pill, or after a pregnancy. In the former case, the hormones in The Pill were masking the symptoms of POI, so you may have been unaware that there was any problem at all.

Symptoms of low estrogen levels (eg. hot flushes, vaginal dryness)

When the ovarian function slows down and then eventually stops all together, the levels of the main female hormone (‘estrogen’) in your bloodstream drop down to low levels. This can lead to several symptoms, such as:

• Hot flushes and night sweats: these may start just before you have your period (when your estrogen levels are naturally at their lowest). If you’re on The Pill, you may notice hot flushes during the week that you take the sugar pills.
• Vaginal dryness, which can lead to discomfort and pain during insertive sex
• Anger, depression and / or anxiety
• Trouble with focus and / or memory

Difficulty falling pregnant

POI is an uncommon cause of infertility. But if you’re <35yo and haven’t conceived naturally after twelve months of trying, or >35yo and haven’t conceived naturally after six months of trying, please see your GP and seek a referral to a gynaecologist with fertility expertise, such as Maven Centre’s Dr Melissa Cameron. Investigations will be performed to look into the possible underlying causes of your subfertility, including screening tests for POI.

Long-term complications of POI

If POI isn’t diagnosed and treated promptly, it can lead to several long-term health implications, as outlined below.

Impaired bone mineral density (osteopaenia and osteoporosis)

Estrogen helps to keep bones strong. So having low estrogen levels (which occurs in POI) can lead to bones being weak, brittle, and more likely to break.

The younger you are when you are diagnosed with POI, the more likely you are to be diagnosed with moderately- or severely-impaired bone density (which are known to osteopaenia and osteoporosis, respectively). To decrease the risk of this occurring, it’s important to take estrogen, vitamin D, and calcium supplements (see details below).

Heart or blood vessel disease

Early lowered estrogen levels (which occurs in untreated POI) may increase the risk of some heart conditions and stroke.

Diagnosis of POI

While it’s important to diagnose POI early, unfortunately over 50% of young women with POI report having seen three of more doctors before blood tests were finally done! If you’re worried about having POI, please ask your doctor to order:

• Follicle stimulating hormone (which will be abnormally high)
• Estrogen (which will be abnormally low)
• Anti-Mullerian hormone (which will be abnormally low)

To rule out alternative causes of irregular / absent periods, your doctor may also order the following blood tests:

• BhCG: to rule out pregnancy
• Thyroid stimulating hormone levels: to rule out under-active thyroid (‘hypothyroidism’)
• Prolactin: to rule out a so-called ‘prolactinoma’

A transvaginal pelvic ultrasound may also be helpful, in that it can quantify your ‘antral follicle count’, which provides a guide as to your ovarian reserve.

If you are diagnosed with POI, your doctor should assess your bone density, by ordering a so-called ‘bone mineral density’ (or ‘DEXA’) scan. This will diagnose whether you have osteopaenia and / or osteoporosis.

For many patients, being diagnosed with POI is a life-altering moment. Feelings of devastation, shock, and confusion are common. It’s important to keep in mind that 50 – 75% of women with POI occasionally ovulate, and that up to 10% are able to have children after their diagnosis. You may find speaking with a clinical psychologist, such as those at Mind in Mind Psychology, helpful.

Treatment of POI

The main goals of POI are to restore estrogen levels, to manage both the symptoms (eg. hot flushes), and prevent complications (such as lower bone mineral density).

Estrogen therapy +/- progesterone

Unless there is a very strong reason not to take estrogen therapy (eg. previous endometrial or breast cancer), your doctor should prescribe estrogen for you, to reduce the risk of osteoporosis and cardiovascular complications in future. Estrogen also helps to maintain sexual health and quality of life. The benefits of estrogen therapy outweigh the risks, up to the age of 50yo or ten years following menopause (whichever is later).

The aim of estrogen therapy is to mimic normal ovarian function as closely as possible. Options include:

• Estradiol tablets (eg. ‘Progynova’ 2mg estradiol daily)
• Estrogen patch (eg. ‘Estradot 100’, ‘Estraderm 100MX’)

These doses are higher than the estrogen component of most hormone replacement therapy given to older post-menopausal women. If you also have vaginal symptoms (such as vaginal dryness and / or discomfort with insertive sex), your doctor may suggest that you also use vaginal estrogen pessaries.

If you still have a uterus (ie. haven’t had a hysterectomy), you’ll also need to take progesterone (to protect the uterine lining from developing pre-cancerous changes). In this case, your options include:

• The combined oral contraceptive pill, or ‘birth control pill’
• A combination of an estrogen medication (as outlined above), plus a separate progesterone medication, such as:
  • Progesterone intrauterine device (‘Mirena’)
  • Micronised progesterone capsule (‘Prometrium’)
  • Medroxyprogesterone acetate tablets (‘Provera’ or ‘Ralovera’)

It’s recommended that you continue hormonal therapy until approximately 50yo.

Fertility treatment

Approximately 75% of women with POI have follicles in their ovaries that can be encouraged to function in future. About 5 – 10% of women with POI will fall pregnant spontaneously, without needing assisted reproductive technologies (such as IVF). For the remaining 90 – 95% of women with POI, options for pregnancy include:

• IVF with oocyte (egg) donation
• IVF with embryo donation
• Adoption

Lifestyle measures

In addition to hormonal therapy +/- fertility treatment, additional measures to aid bone health include:

• Stopping smoking
• A healthy diet
• Adequate vitamin D and calcium intake +/- supplements
• Regular weight-bearing and aerobic exercise

Emotional and psychological support

Understandably, many women find being diagnosed with POI emotionally distressing: it may disrupt their life plans, hopes and dreams with regards to future pregnancies. Some may develop depression and / or anxiety as a result. If you’re worried about your mental health, feeling intense grief or loss, or want to talk over your diagnosis with a trained professional, seek out a qualified clinical health psychologist, such as an appropriate clinician at Mind in Mind Psychology.

Topic area frequently asked questions (FAQs)

Can I still ovulate or fall pregnant if I have POI?

Approximately 5 – 10% of women with POI may continue to experience a month or two of periods and ovulation (the ovaries producing an egg) after their diagnosis. This can occur many years after their initial diagnosis.

Are POI and ‘low ovarian reserve’ the same thing?

Low / diminished ovarian reserve is not the same as POI: it is a term used in the context of infertility investigations and treatment. ‘Low ovarian reserve’ refers to women with abnormal ovarian reserve investigation results (eg. abnormally low anti-Mullerian hormone blood test result and / or abnormally low antral follicle count on ultrasound). This terms is also used in the context of women whose ovaries respond poorly to ovarian stimulation medications.

My period is a little bit irregular. When should I see a doctor?

If your period is late, and there is a chance you could be pregnant: please do a urine pregnancy test!

If you’ve missed your period for three months or more, and are not pregnant, it’s worth seeing your healthcare team to figure out if there’s an underlying cause. You may miss your period for any number of reasons (eg. stress, change in diet or exercise habits). But it’s best to get a check-up with your GP whenever your menstrual cycle changes.

I’m worried I might develop POI. Should I have my eggs frozen?

If you have the following conditions, you may be at risk of developing POI:

• Fragile X pre-mutation
• Turner mosaic
• Autoimmune polyglandular syndrome type 2

In this situation, it would be worth discussing egg freezing with a fertility specialist: at Maven Centre, our fertility expert is Dr Melissa Cameron.

If you’ve already been diagnosed with POI, unfortunately there’s less to be gained from going through the egg freezing process, as there are already so few eggs left in the ovaries.

Conclusion

If you have irregular or absent periods, please see your GP. They will suggest various tests to rule out pregnancy, and investigate possible Primary Ovarian Insufficiency. Being diagnosed with POI can be life-altering, but doesn’t need to be life-devastating: with appropriate hormonal, bone, and mental health support, a full and satisfying life can await!

If you’d like more information and resources about POI, please visit the website of UK charity The Daisy Network.