Premature Ovarian Insufficiency – a silent struggle before 40 (and beyond)
Premature Ovarian Insufficiency (POI), previously, but still commonly known as Premature Ovarian Failure (POF), and Premature Menopause, is a condition where the ovaries stop working or a loss of ovarian function before the age of 40. It affects between 1-3% of the global female population; 1% of women under 40, 0.1% under 30, and 0.01% under 20 worldwide (ESHRE, 2024). I was diagnosed with idiopathic, wherein the cause is unknown but is considered likely genetic, POI a few years ago at age 36, with symptoms starting decades before, likely in my late teens or early 20’s, and certainly from the age of about 29.
Over the years, I started having irregular menstrual cycles, skipping several months of periods, some normal and then increasingly lighter and shorter. I also experienced joint ache, headaches, dizziness, anxiety, musculoskeletal injuries (rotator cuff and ligament injuries), which I had not known at the time were symptoms of POI. I kept going to the doctor with these symptoms and my thyroid would be tested, a full blood panel done, but frustratingly no clinician thought to check my hormone levels. These tests were important because many of my symptoms overlapped with other conditions and diseases.
POI brings an earlier and often abrupt loss of hormones, the effects which can lead to social withdrawal, fatigue and anxiety – all of which affect long-term health, mental well-being, relationships, making it challenging to interact with one’s peers with enthusiasm, affecting career progression and of course, fertility. It is a multilayered diagnosis with immediate and long-term effects on the body especially when unmanaged (not using HRT).
I know both personally and from others, what a challenging journey it is to advocate for oneself when experiencing gynaecological conditions such as POI. It is usually a very lonely and isolating experience – not least because not many of one’s peers are experiencing the same (whereas in case of menopause, every woman living long enough will go through this).
About POI
POI is an under-researched condition, therefore about 70-80% of cases have an unknown or idiopathic cause. Even among clinicians there is limited awareness of its diagnosis and management. Causes that are known include iatrogenic (caused by chemotherapy and radiation for cancer treatment), genetic (e.g., Fragile X, Turner’s Syndrome, Turner Mosaic Syndrome, etc), autoimmune conditions (such as the immune system attacking ovarian tissue), and certain viral illnesses. POI can be diagnosed as young as puberty (absent puberty) or as late as at 39 years of age. In the 20-30’s age group it is typically discovered because of fertility investigations.
Regarding management of POI, because little is known about the condition and the fact that symptoms present similarly to menopause, clinical guidelines for POI are extrapolated from existing menopause guidelines. The key differences being women diagnosed with POI typically need higher doses of hormone replacement therapy (HRT) or PET (Progesterone, Oestrogen and Testosterone) to mimic what they are otherwise missing or very low and long-term management due to the impact on the body of missing key hormones – such as osteoporosis, heart health and brain health. In natural age menopause, hormones are naturally declining, so doses are usually lower.
The role of hormones
Ovaries are responsible for more than reproduction through releasing an egg. They are part of the body’s endocrine system, producing critical hormones for bodily functions – namely Oestrogen, Progesterone and Testosterone (the least studied in women). These three hormones play a key role across all organs in the body, which include, maintaining cardiovascular (heart), bone and brain health. They affect skin, eyes, genitals (vagina, vulva, clitoris – discomfort and painful intercourse/sex), the bladder (increase in urinary tract infections (UTI) and incontinence), the intestines and digestive health, eyes, joints, all general mucous membranes, and much more, across the body. It used to be thought the ovaries and the hormones they produce were only responsible for and affected the reproductive organs – breasts, uterus and ovaries - and for pregnancy. We now know these hormones are critical for the whole body including the brain (Mosconi, 2024). This is why POI tends to have a profound effect on a woman’s body and mental health. This applies to perimenopause, menopause and post menopause as well – all of which are whole-body conditions.
Clinical guidelines
The 2024 ESHRE Guideline on POI recommends four to six months of disordered (irregular or missed) periods to prompt a blood test for elevated FSH (25 and above for a POI diagnosis) and low Oestrogen.
In POI, it is critical to replace these hormones not being produced by the ovaries. While infertility and symptom management (think joint aches, brain fog, incontinence and UTIs, hot flashes, incontinence, insomnia, anxiety, to name just a few) often feel like the most pressing issues to the patient, the long-term impact on the body can show up some years after diagnosis. The longer a woman with POI is without sufficient levels of these hormones, the higher her risks of brain health (cognitive decline, dementia), bone thinning (osteopenia, osteoporosis and fracture risk) and heart or cardiovascular health (cholesterol, etc) as she ages.
Therefore, the main course of management is HRT or PET. Routes for these include transdermal - as in absorbed through the skin (adhesive patches, gels, sprays and creams), oral (tablet or capsule form) or medical devices (Intrauterine system – IUS – otherwise known as the hormone coil which is inserted into the uterus for Progesterone). Oestrogen is the main hormone replaced. Progesterone is mandatory if a woman still has a uterus and is taking Oestrogen. This is to protect the endometrial lining from thickening too much (which can be dangerous) due to Oestrogen. Testosterone is optional and can help with symptoms. While during menopause hormones are naturally gradually declining in a woman, in POI they should not be declining, rather fluctuating monthly – a dance between oestrogen and progesterone – resulting in a menstrual cycle (periods) or pregnancy.
In Pakistan, HRT or PET drugs are very limited. While Tibolone, Progesterone tablets, pessaries, gel and the IUS and implant (for progesterone) are available, Oestrogen tablets and vaginal Oestrogen cream are sporadically available, transdermal Oestrogen options are not available, and Testosterone is available in male formulations only. The type and combination of HRT need to be adjusted to suit each woman, so individualised care is important. What dosages and types of HRT work for one woman, may not work well for another. This is why having more than one HRT option is important.
POI (un)awareness
South Asia (Bulletti et al, 2005) has some of the highest rates of POI, especially among lower socio-economic brackets and this is multifactorial. Contributing factors may include malnutrition, poor health seeking behaviours leaving viruses and sexually transmitted diseases and other infections unaddressed, environmental exposures or endocrine disruptors (unsafe levels of chemicals and pesticides) and a lack of hormone replacement counselling, and availability of suitable HRT options, after gynaecological surgeries which include the removal of the ovaries and uterus (Panay, 2025).
Through my experience of POI, which has involved a steep learning curve, I have also learnt a lot about menopause and its management. I have come to realise how women’s health is approached - as reproductive vessels. There is support and awareness for women from puberty through to pregnancy and post-partum (childbirth and the time just after). And then it just stops. There is a whole demographic of (often quite vulnerable) women left without proper, evidence-based support. This is not to say women of "childbearing" age are considerably better supported, but by comparison there is limited focus on and support for it.
I have become passionate about helping other women going through these conditions, creating awareness of POI especially in Pakistan where gynaecological conditions are discussed in hushed tones, if at all. About a decade ago, menstrual health was a taboo barely spoken of. Today, we have billboards and advertisements of period products. A woman of natural age menopause once said to me, “it’s not that I want access to HRT. I want the knowledge to not be frightened by my symptoms, to know where to attribute them, to know I’m not going crazy, to not be dismissed”. As an example, it is thanks to HRT and psychosocial support that I have been able to think clearly enough to articulate my thoughts in this article and advocate for this cause with confidence, and I am so grateful to modern medicine for it.
To help widen the conversations around POI, to connect women with POI with each other, to provide psychosocial support alongside physiological (medication) support, I have created a dedicated Instagram account (@speakup_for_poi), and a closed Facebook group for women living in Pakistan, and through the Daisy Network (a UK-based, global charity dedicated to POI) a closed Facebook group for South Asian diaspora globally. Societies across the world tend to place a woman’s worth on her reproductive and economic value, both of which can take a hit with a POI diagnosis. If I can help even one other woman feel less alone in her experience of a POI diagnosis and management of it, putting my story out there will have been worth it.
Naomi Alesworth is Pakistani and British and grew up in Karachi, Pakistan where she has also worked. She is not a doctor, however this article has been reviewed for medical accuracy by Prof. Dr. Sadiah Ahsan Pal, who has a clinic in Karachi, Pakistan and Dr Farah Ahmed (IG @drfarahwomenshealth), General Practitioner (GP) in the UK with Special Interest in Women’s Health & Menopause.