can occur spontaneously or be secondary to medical therapies. It is estimated that spontaneous POI affects 1% of the female population
the combined oral contraceptive pill (COCP), fertility drugs and prior hormone replacement therapy (HRT) do not cause POI, but cessation of these therapies may unmask undiagnosed POI
Causes
Spontaneous POI
Idiopathic – most common cause of spontaneous POI
Genetic causes (10% of POI) –
Turner syndrome (45XO) – most common genetic cause
Smoking – associated with earlier onset of menopause
Iatrogenic POI
Chemotherapy – particularly alkylating agents and dependent on cumulative dose
Radiotherapy – dependent on cumulative dose and field of exposure
Bilateral oophorectomy
Other pelvic surgery has been associated with early age of menopause and/or reduced ovarian reserve –
Single oophorectomy, hysterectomy, uterine artery embolization, bilateral ovarian surgery for cysts or endometriosis
Clinical presentation
can be variable
most common presenting symptom is
menstrual disturbance: oligomenorrhoea or amenorrhoea
differential diagnosis of amenorrhea includes:
Pregnancy.
Polycystic ovarian syndrome.
Hypothalamic amenorrhea.
Pituitary disease.
Hypothyroidism and hyperthyroidism.
Uterine abnormalities.
Chronic medical illness secondary to poorly controlled diabetes or celiac disease.
Lifestyle habits (excessive exercise and poor caloric intake)
Women with primary amenorrhoea are unlikely to experience menopausal symptoms.
Menopausal symptoms (eg hot flushes and urogynaecological and sexual changes) may be more severe in women with premature menopause, compared with natural menopause
Infertility
is a key feature of POI given the loss of ovarian reserve.
In women with spontaneous POI, approximately 5% can spontaneously ovulate and conceive
diagnostic approach:
History
Sexual Development History (if possible Primary Amenorrhea)
Breast development
Pubic hair development
Menstrual and Gynecologic history
Age at Menarche
Menstrual Cycle characteristics
Premenstrual symptoms
Last spontaneous menstrual cycle
Sexual Activity
Family History
Genetic anomaly
Menarche age of onset in first degree relatives
male mental retardation (suggest Fragile X syndrome)
Obstetric history
Past medical history
Chronic disease history
Chemotherapy
Prior pelvic surgeries, irradiation, or chemotherapy
Eating Disorder or Female Athlete Triad (Functional Hypothalamic Amenorrhea)
Diet, Weight change, or Eating Disorder
Overtraining or Exercise addiction
History of Stress Fractures
Prolactinoma symptoms
Galactorrhea
Headache
Bitemporal field cut
Hyperandrogenism or Polycystic ovary symptoms and signs
Hirsutism
Acne Vulgaris
Growth abnormalities
Short Stature (Turner Syndrome)
Symptoms of adrenal insufficiency, including the following:
Orthostatic hypotension
Skin hyperpigmentation
Unexplained weakness
Salt craving
Abdominal pain
Anorexia
Vasomotor Symptoms of Menopause
Hot Flushes
Hypothyroidism symptoms
cold intolerance
Palpitations
Constipation
Major Depression
Anosmia
Kallmann Syndrome
Physical examination
Signs of hypoestrogenism
Vaginal dryness or atrophy
Breast Exam
Normal Breast development suggests circulating Estrogens (Primary Amenorrhea)
Galactorrhea (Hyperprolactinemia)
Gynecologic exam
Rule out uterine or ovarian anomaly
Vaginal Atrophy (red or thin vaginal mucosa)
Low Estrogen
Transverse septum or Imperforate Hymen
Outflow tract obstruction
Shortened Vagina
Uterine outflow obstruction
Mullerian Agenesis
Absent Cervix or Uterus
Mullerian Agenesis
Androgen Insensitivity Syndrome
Clitoromegaly
Androgen Secreting tumor
Congenital Adrenal Hyperplasia
5a-Reductase Deficiency
Body Mass Index (and height and weight)
Low BMI in Functional Hypothalamic Amenorrhea
High in Polycystic Ovary Syndrome
Hyperandrogenism or Polycystic Ovary Syndrome
Hirsutism
Acne Vulgaris
Acanthosis Nigricans
Male pattern baldness
Cushing’s Disease
Central Obesity
Buffalo Hump
Hypertension
Hirsutism
Wide, purple abdominal and thigh striae
Thyromegaly
Turner Syndrome
Webbed Neck
Short Stature
Low hairline
Hot flashes and night sweats
Diagnosis
POI should be considered
in any woman aged <40 years presenting with history of menstrual disturbance (oligomenorrhoea or amenorrhoea
girls who have not undergone menarche by 15 years of age (98% of adolescents will have their first menses by this age)
Tests
Pregnancy test
FSH, LH, estradiol
Diagnosis: FSH levels in the menopausal range(>40 IU)
2 occasions at least 4-6 weeks apart
woman aged <40 years
after >4 months of amenorrhoea/menstrual irregularity
It is important that women are not taking
hormonal contraceptives or HRT
to ensure accurate interpretation of the hormone levels.
These agents must be withdrawn for at least 6 weeks prior to hormone measurements
Standard blood chemistry – Fasting glucose, electrolytes, and creatinine
Karyotype
to exclude Turner syndrome and other chromosomal abnormalities
test for fragile X chromosome (FMR1 premutation)
Autoimmune screen
Thyroid-stimulating hormone (TSH)
Antithyroid peroxidase antibody
Coeliac screening
Serum adrenal antibodies
Pelvic USS
Uterine polyps, fibroids and abnormalities of the Müllerian tract
Bone density by dual-energy x-ray absorptiometry (DEXA) scan
Anti-Müllerian hormone (AMH)
AMH is produced by the granulosa cells of the pre-antral and antral follicles, thereby reflecting the size of the primordial follicle pool.
Serum AMH concentration is inversely related to female age and shows minimal variation both within and between cycles.
Therefore, testing on any day of the menstrual cycle is appropriate.
Results will often be reported as the absolute number as well as the centile in relation to female age, which assists interpretation.
Elevated AMH is predictive of an excessive response to controlled ovarian hyperstimulation during ART
low AMH is predictive of an increased risk of poor ovarian response.
For women attempting spontaneous conception, AMH correlates poorly with fecundity
counselling regarding contraceptive options is important for women not desiring pregnancy
Pregnancy
10% have spontaneous resolution and chance of pregnancy
COCP can provide both hormone replacement and contraception and, if prescribed, women should be advised to take it continuously or long cycle, without the inactive pills, to avoid intermittent periods of symptomatic oestrogen deprivation
provide contraception but not oestrogen replacement.
An option would be to use transdermal oestrogen with the levonorgestrel IUD, thereby providing contraception, symptom management and prevention of long-term sequelae.
treatment of urogenital symptoms
vaginal oestrogen or lubricant to treat dyspareunia
Manage psychosocial symptoms
depression and anxiety
negative body image
decreased sexual function
reduced confidence
grief at the loss of femininity and fertility
fear of long-term health consequences related to POI
concerns regarding the effects on the relationship with their partner
