History

Fact Explanation
Absence of menstruation [1] This could be primary (absence of menarche) or secondary (absence of menstruation before the age of 40 years) amennorrhoea. [1]
Absence of secondary sexual characteristics [1] Occurs in severe form of ovarian failure, in early lose of follicular pool. [1]
Infertility [1] Due to depletion of ovarian follicles [1]
Hot flushes, heat intolerance, night sweats. [1][2] These are common vasomotor symptoms associated with menopause which is seen ovarian failure. [1]
Depression, anxiety, irritability, fatigue, sleep disturbance [1] These psychological symptoms equivalent to menopause occurs. [1]
Pathological fractures [1] Prolonged lack of oestrogen causes osteopenia which results in early onset osteoporosis resulting in frequent fractures even in minor trauma. [1]
Decreased libido [1][2] Sexual drive is reduced due to lack of sexual hormones, vaginal dryness[1] may also be a contributing factor.
Forgetfulness, disorientation Increased risk of Alzheimer's disease due to lack of sex hormones. [1]
Chest pain/ tightness, reduced excercise tolerence, past myocardial infarctions Increased risk of hypercholesterolemia and ischemic disease due to lack of sex hormones. [1]
History of chemotherapy, radiotherapy, pelvic surgery [2] These can result in postprocedural ovarian failure. Pelvic surgery such as that for endometriosis, ovarian cyst removal are known to cause postprocedural ovarian failure.[3]
References
  1. BECK-PECCOZ Paolo, PERSANI Luca, Premature ovarian failure Orphanet J Rare Dis [online] 2006 December [viewed 27 August 2014] Available from: doi:10.1186/1750-1172-1-9
  2. ARORA PUNEET, POLSON DAVID W. Diagnosis and management of premature ovarian failure. [online] December, 13(2):67-72 [viewed 27 August 2014] Available from: doi:10.1576/toag.13.2.67.27648
  3. JEWELEWICZ R, SCHWARTZ M. Premature ovarian failure. Bull N Y Acad Med [online] 1986 Apr, 62(3):219-236 [viewed 27 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1629109

Examination

Fact Explanation
Lack of secondary sexual characteristics: Poor breast formation, lack of pubic hair [1] This occurs is severe form of ovarian failure when early depletion of follicles occur and patients present with primary amenorrhoea. [1]
Short stature [1] Due to poor growth spurt in severe form of ovarian failure patients do not achieve the normal height. [1]
Hirsutism (excessive body and facial hair) [1][2] Occurs due to unopposed action of androgen formed in adrenal glands [1]
Abdominal examination May reveal past laparoscopy/ laparotomy scars
Vaginal examination Will show dry vagina [1] and sparse pubic hair
References
  1. BECK-PECCOZ Paolo, PERSANI Luca, Premature ovarian failure Orphanet J Rare Dis [online] 2006 December [viewed 27 August 2014] Available from: doi:10.1186/1750-1172-1-9
  2. ARORA PUNEET, POLSON DAVID W. Diagnosis and management of premature ovarian failure. [online] December, 13(2):67-72 [viewed 27 August 2014] Available from: doi:10.1576/toag.13.2.67.27648

Differential Diagnoses

Fact Explanation
Defects in X chromosome Eg: Turner syndrome, Fragile X syndrome [1][4] Ovarian dysgenesis causes primary amenorrhoea in these conditions, typical physical feature will aid in diagnosis.
Autoimmune [1][4] Eg: Polyglandular autoimmune syndrome, AIRE gene mutation causing autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) [1]
Surgery [1][3][4] Pelvic surgeries can result in ovarian failure mainly after endometriosis. Care should be taken to preserve as much as ovary as possible along with its blood supply during surgeries. [3]
Post cancer treatments (chemotherapy, radiotherapy) [1][2][4] Ovarian, abdominal, pelvic and spinal radiotherapy irradiation, chemotherapy including alkylating agent and/or procarbazine may result in disruption of ova and its maturation resulting in postprocedural ovarian failure. [1][2]
Infections [1] Herpes zoster and cytomegalovirus can cause premature ovarian failure [1]
Drugs [1][3] Drugs such as methotrexate, actinomycin, adriomycin, dauomycin, hydroxyurea, L-asparaginase are known to cause ovarian failure. [3]
Syndromic conditions [1] Galactosemia, congenital disorders of glycosylation, pseudohypoparathyroidism (PHP) type Ia, blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) also results in premature ovarian failure. [1]
Isolated defects in receptors [1][4] Receptor mutations of follicle stimulating hormone (FSH) and luteinizing hormone (LH) will result in reduced stimulation of ovaries by these hormones resulting in lack of follicular stimulation. They can present as either primary or secondary amenorrhoea depending on the degree of defective receptors [1]
Other mutations FOXL2, BMP15 mutations can also result in premature ovarian failure.
References
  1. BECK-PECCOZ Paolo, PERSANI Luca, Premature ovarian failure Orphanet J Rare Dis [online] 2006 December [viewed 27 August 2014] Available from: doi:10.1186/1750-1172-1-9
  2. GREEN DM, SKLAR CA, BOICE JD JR, MULVIHILL JJ, WHITTON JA, STOVALL M, YASUI Y. Ovarian Failure and Reproductive Outcomes After Childhood Cancer Treatment: Results From the Childhood Cancer Survivor Study J Clin Oncol [online] 2009 May 10, 27(14):2374-2381 [viewed 27 August 2014] Available from: doi:10.1200/JCO.2008.21.1839
  3. JEWELEWICZ R, SCHWARTZ M. Premature ovarian failure. Bull N Y Acad Med [online] 1986 Apr, 62(3):219-236 [viewed 27 August 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1629109
  4. ARORA PUNEET, POLSON DAVID W. Diagnosis and management of premature ovarian failure. [online] December, 13(2):67-72 [viewed 27 August 2014] Available from: doi:10.1576/toag.13.2.67.27648

Investigations - for Diagnosis

Fact Explanation
Estrogen levels [1] These gonadal hormone levels will be low due to lack of ovarian follicles to synthesis them. [1]
FSH and LH levels [1] Synthesis of these gonadotropins from pituitary is controlled by negative feedback from the gonadal hormones. Since gonadal hormonal levels are low, there is no negative feedback thus gonadotropins level will be very high. [1] FSH levels are usually higher than LH levels (FSH >30 U/L)
Ultrasound scan of the pelvis [1] This will show streaky ovaries without any growing follicles [1]
inhibin B, anti-mullerian hormone (AMH) levels [1] These are of ovarian origin and lack of inhibin B indicates low ovarian reserve even prior to FSH elevation. [1]
References
  1. BECK-PECCOZ Paolo, PERSANI Luca, Premature ovarian failure Orphanet J Rare Dis [online] 2006 December [viewed 27 August 2014] Available from: doi:10.1186/1750-1172-1-9

Management - General Measures

Fact Explanation
Emotional support [1] Postprocedural ovarian failure resulting in premature ovarian failure will cause symptoms of menopause and infertility and affected women should be provided with adequate emotional support at all times.
Multi disciplinary management with councellor and psychologist [2][3] Prior to procedure counseling regarding possible infertility/ oocyte preservation and early menopause should be given. [2][3]
References
  1. BECK-PECCOZ Paolo, PERSANI Luca, Premature ovarian failure Orphanet J Rare Dis [online] 2006 December [viewed 27 August 2014] Available from: doi:10.1186/1750-1172-1-9
  2. GREEN DM, SKLAR CA, BOICE JD JR, MULVIHILL JJ, WHITTON JA, STOVALL M, YASUI Y. Ovarian Failure and Reproductive Outcomes After Childhood Cancer Treatment: Results From the Childhood Cancer Survivor Study J Clin Oncol [online] 2009 May 10, 27(14):2374-2381 [viewed 27 August 2014] Available from: doi:10.1200/JCO.2008.21.1839
  3. ARORA PUNEET, POLSON DAVID W. Diagnosis and management of premature ovarian failure. [online] December, 13(2):67-72 [viewed 27 August 2014] Available from: doi:10.1576/toag.13.2.67.27648

Management - Specific Treatments

Fact Explanation
Hormone replacement therapy- oestrogen and progesterone supplements can be given in various routes ( oral, vaginal, transdermal) [1][3] Exogenous oestrogen has proven of benefit for enhancing bone density and cardiovascular function. It increases high density lipoprotein and reduce total cholesterol and low density lipoprotein. It should be started as early as possible and should be continued till age of menopause and reviewed afterwards. [3] Transdermal estradiol and vaginal progesterone has been proven to have higher cardiovascular benefit than oral ethinylestradiol and norethisterone [3]
Use of donated ovum to achieve fertility [1] This is the only possible way of achieving fertility. [1]
Cryopreservation of oocyte, embryo or ovarian tissue [1][2] They can be kept frozen and used later to achieve pregnancy, this method is widely used in expected cases of ovarian failure after high radiotherapy(>10 Gy) and after chemotherapy with alkylating agents and procarbazine [1][2]
Calcium-rich diet and vitamin D supplementation [3] This enhances bone density. Patient should also be advised regarding increasing physical activity and reducing smoking and alcohol to achieve this. [3]
Transplantation of ovarian cortex/ ovary [3] This should be obtained from a monozygotic twin thus not available all the time, but pregnancy after transplantation have been reported. [3]
Gonadal shielding, ovarian transposition [3] These methods are used prior to radiation to save the ovaries from being irradiated. [3]
References
  1. BECK-PECCOZ Paolo, PERSANI Luca, Premature ovarian failure Orphanet J Rare Dis [online] 2006 December [viewed 27 August 2014] Available from: doi:10.1186/1750-1172-1-9
  2. GREEN DM, SKLAR CA, BOICE JD JR, MULVIHILL JJ, WHITTON JA, STOVALL M, YASUI Y. Ovarian Failure and Reproductive Outcomes After Childhood Cancer Treatment: Results From the Childhood Cancer Survivor Study J Clin Oncol [online] 2009 May 10, 27(14):2374-2381 [viewed 27 August 2014] Available from: doi:10.1200/JCO.2008.21.1839
  3. ARORA PUNEET, POLSON DAVID W. Diagnosis and management of premature ovarian failure. [online] December, 13(2):67-72 [viewed 27 August 2014] Available from: doi:10.1576/toag.13.2.67.27648