Premature Ovarian Failure

A client seen in our specialist reproductive endocrinology clinic aged 37 years stopped seeing her menstruation at the age of 34 years. She is seriously concerned. She has been to several hospitals and was diagnosed with premature ovarian failure. What are her treatment options?

Furthermore, what is premature ovarian failure? What are the causes? How can one know, one has it? What are the symptoms? How is it diagnosed? Are there any treatments for it? Is it the same as menopause?

Premature Ovarian Failure (POF) is defined as ovarian failure and cessation of ovarian functions characteristically before age 40 years, alluding to the fact that it can occur in the 20s and 30s as well. It can be self-limiting, that is, irregular menstruation or normal menstruation might recur, and occasionally spontaneous pregnancy may occur in the remission stage. Usually, the menstrual cycles becomes very irregular or might stop altogether.

It is not the same as premature menopause, where menstruation stops permanently and chance of spontaneous pregnancy is nil. Menopause naturally starts between the ages of 50 or 51 years. It is noteworthy that, 1% become menopausal before 40 years of age and 1% of women menstruate at age 60. POF can occur before, during and after puberty. Approximately 1% of women are estimated to have POF before 40years. Its prevalence is about 10% to 28% in those who have not seen their periods beyond the normal expected age 9 to 14 years.

CAUSES

1. Genetic – Turners syndrome, Gonal dysgenesis, Abnormal Chromosomes.
2. Family history – Siblings/cousins/mother may have been diagnosed with POF. Genetic polymorphism of FSH/ LH receptors. Families with ovarian cancer (BRCA1 gene mutation).
3. Environmental Pollution – Smoking, diet polluted with toxic chemicals, exposures to pesticides.
4. Auto immune disease – poly-endocrinopathies including diabetes mellitus, thyroiditis, ovaritis etc.
5. Infections – viral infections that affect the ovaries – mumps for example
6. Chemotherapy/Radiotherapy
7. Idiopathic – no known cause(s) found

RISK FACTORS

1. Family history of POF
2. Families with ovarian/breast cancers are common
3. Autoimmune endocrinopathies
4. High levels of FSH, E2,
5. Prolonged cessation of menstruation or amenorrhea
6. Repeated ovarian surgeries.

SYMPTOMS – most patients will present with a clinical history – a combination of…

1. No menstruation ever up to or beyond 18 years of age. POF can occur before/during/after menstruation.
2. If it occurs before menses – no breast & other female secondary sex characteristics will be present. No menstrual flow.
3. A detailed family history history is important for those whose mother, siblings, and other close relatives first, second or third degrees have POF.
4. Skin diseases vitiligo, rheumatoid arthritis, systemic lupus erythematosus; symptoms and signs may be present.
5. POF is usually associated with irregular menstruation or complete cessation of menstruation.
6. Infertility.

INVESTIGATIONS and DIAGNOSIS

Blood tests, pelvic ultrasound scan, breast scans or mammogram and dexa bone scan.

             Pregnancy test to rule out an ongoing pregnancy.

             Blood tests for hormone imbalance to evaluate sex hormones (AMH, FSH, LH, prolactin, estradiol etc.). This is to elucidate any derangement in the physiology of the hypothalamo-pituitary-ovarian axis.

             Blood tests for evaluation and chromosomal DNA composition (karyotype), FMR1 gene test for the gene associated with congenital fragile X genetic disease.

             Blood tests for serum auto-antibodies – tests for– antibodies directed against ovarian, thyroid, DNA, imicrosomal, liver tissues and rheumatoid factor.

             Pelvic USS to examine the uterus and ovaries. Both ovaries may be atrophic.

             Dexa bone scan to check bone densitometry (I do breast scan/mammogram as well especially in those with family history of breast and/or ovarian cancer).

Treatments

Psychological counselling for crucial support to the patients. In developed societies – UK, USA, Europe POF support groups are available and patients can join for medical and psychological supports, counseling and bonding (if you think you have POF please contact us especially, if you are interested in becoming a member of a local POF support group.

Long term treatments include Hormone Replacement Therapy to prevent osteoporosis and its symptoms – for example menopausal. Vaginal estrogen pessaries to prevent perineal, vulva and vaginal dryness, which in some cases can extreme and very discomforting, Testosterone additions is sometimes prescribed to improve libido.

Broad range of Infertility treatments are available for those fertility concerns. However, POF can be self-limiting, therefore, spontaneous fertility can occur. IVF with egg donation and surrogacy is recommended in those majority with unremitting POF.

Ovary transplant is also a treatment modalities and it is to replace failed .atrophic ovaries.

Adoption as a first option or a last resort, if all else prove abortive.

Our client discussed above had egg donor IVF treatment cycle and got pregnant, now nursing a baby boy.

By Dr Lateef Akinola, MSc., PhD, MBA, MRCOG, Consultant Gynaecologist, Fertility specialist & Obstetrician