Ovaries + hormonal axis Flashcards
what is the definition of primary amenorrhoea
not starting menstruation:
- or having any other evidence of pubertal development by age 14.
- by 16 years of age where there are other signs of puberty (e.g. breast bud development).
What is considered normal puberty in females
- 8-14 in girls .
- takes about 4 years from start to finish.
- Girls have their pubertal growth spurt earlier in puberty than boys.
- starts with developing breast buds, then pubic hair and finally starting their periods (usually about 2 years from the start of puberty).
What is considered normal puberty in males
- 9-15 in boys
- boys growth spurt is later in boy
What is Hypogonadotropic Hypogonadism
- deficiency of LH and FSH (gonadotrophins) from the anterior pituitary gland
- Since there are no gonadotrophins simulating the testes or ovaries (the gonads), they do not respond by producing sex hormones (testosterone and oestrogen)
- Therefore, a lack of gonadotrophins (“hypogonadotrophic”) leads to underproductive gonads (“hypogonadism”).
What does Hypogonadotrophic hypogonadism tell you
- problem is in the hypothalamus or the pituitary gland.
- If you send a hormonal profile, you will find a low LH and a low FSH result.
what is Hypergonadotrophic Hypogonadism
- the gonads fail to response to stimulation from the gonadotrophins.
- As there is no negative feedback from the sex hormones (testosterone and oestrogen) the anterior pituitary produces higher levels of gonadotrophins to try harder to stimulate the gonads.
- Therefore you get high gonadotrophins (“hypergonadotrophic“) and low sex hormones (“hypogonadism“).
What does Hypergonadotrophic hypogonadism tell you
The problem is in the ovaries. If you send a hormonal profile, you will find a high LH and high FSH result.
What other endocrine causes can lead to amenorhoea
Hypothyroid Hyperprolactinaemia Congenital Adrenal Hyperplasia Turners Syndrome Androgen Insensitivity Syndrome
How do you investigate amenorrhoea
- Look for evidence of puberty
- Look for Hypothalamic causes
- Signs of androgen excess, thyroid problems or high prolactin (i.e. galactorrhea)
- Any dysmorphic features
- Abdominal and pelvic examination/ultrasound
- Hormone tests (LH, FSH, TSH and prolactin level)
What may you look at to look for signs of puberty
- Height and weight
- Assessing for the development of pubic hair, breast tissue and acne.
How do you investigate hypothalamic causes of amenorrhoea
- History of excessive exercise, stress, eating disorder and chronic disease.
- Examination revealing low BMI or signs of an eating disorder or chronic disease.
How do you manage primary amenorrhoea
- encourage a reduction in stress and healthy weight gain.
- Treat/control underlying hormonal conditions
- Primary ovarian failure or polycystic ovarian syndrome, consider the combined oral contraceptive pill.
What is one of the biggest risk of primary amenorrhoea
- Osteoporosis
How do you treat patients with permenant primary amenorrhoea to reduce the risk of osteoporosis
- Ensure adequate vitamin D and calcium
- Cyclical hormone replacement therapy, for example starting the combined oral contraceptive pill
What is secondary amenorrhoea
- no menstruation for more than 3 months after having previously started periods.
- Usually investigation would not be indicated until it has lasted more than 6 months.
What are the causes of secondary amenorrhoea
- Pregnancy (most common cause)
- Menopause
- Some Hypothalamic causes
- Pituitary issues
- Ovarian issues
- Uterine causes: Ashermans Syndrome
- hypothyroid
What hypothalamic issues can lead to secondary amenorrhoea
- Excessive exercise
- Low weight / eating disorders
- Chronic disease
- Psychological causes (e.g. stress)
Why do some hypothalamic issues lead to secondary amenorrhoea
- Physiological stress stops the hypothalamus from producing GnRH.
- This is a way of preventing pregnancy in situations where the body may not be fit for it:
How can pituitary issues lead to secondary amenorrhoea
Pituitary Tumour (e.g. prolactinoma) Pituitary Failure (e.g. Sheehan Syndrome)
What ovarian issues can lead to secondary amenorrhoea
Polycystic Ovarian Syndrome (PCOS)
Premature ovarian failure
Menopause
What is Hyperprolactinaemia
- High prolactin levels act on the hypothalamus to prevent release of GnRH.
- Without GnRH there is no release of LH and FSH and so there is hypogonadotropic hypogonadism
What is galactorrhoea
milky secretion from the breasts as a result of high prolactin levels (30% of high prolactin will have galactorrhoea)
What is the most common cause of galactorrhoea
pituitary adenoma
What investigations should you undertake if a woman presents with high prolactin
- CT / MRI head to look for a pituitary tumour.
- Often there is a microadenoma and won’t show up on the initial scan so close follow up is required in case they develop a tumour later.
How do we manage hyperprolactinaemia
- Often no treatment is required.
- Dopamine agonists (bromocryptine / cabergoline) can reduce prolactin levels.
- These medication are commonly used in conditions such as prolactinomas, Parkinson’s Disease and Acromegaly.
What LH/FSH levels suggest primary ovarian failure
High FSH
What LH/FSH levels suggest PCOS
High LH or LH:FSH ratio suggests PCOS
What hormonal investigations should you do when investigating amenorrhoea
- FSH/LH
- Prolactin
- TSH
- Progesterone stimulation test
What is the progesterone stimulation test
Tests whether there is sufficient oestrogen.
Insufficient oestrogen would suggest causes like PCOS, ovarian failure or menopause.
What does the progesterone stimulation test show
- No withdrawal bleed = low oestrogen preventing her building up the endometrium
- Withdrawal bleed = anovulation preventing menstruation
How do you do the progesterone stimulation test
- Involves giving progestogen for 5 days (medroxyprogesterone acetate 5mg) then stopped.
- Menstruation should occur within 7 days of stopping progesterone.
What is Androgen insensitivity syndrome
- insensitivity of the body to androgens (e.g. testosterone), so normal male sexual characteristics do not develop.
- This results in a female phenotype other than the internal pelvic organs.
- female external genitalia and breast tissue however internally there are testes in the abdomen or inguinal canal and no uterus, upper vagina, fallopian tubes or ovaries.
The production of which hormone prevents males from developing female sexual organs
mullerian inhibiting factor
What Issues lead to androgen insensitivity syndrome
- X linked condition.
- Male karyotype (46 XY).
What are the consequences of androgen insensitivity
- no pubic hair, facial hair or male type muscle development.
- Patients are infertile and there is a risk of testicular cancer unless the testes are removed.
What is the management of androgen insensitivity syndrome
- Generally raised as female, but this is sensitive and tailored to the individual.
- Oestrogen therapy.
- Bilateral orchidectomy (removal of the testes)
What causes pre-menstrual syndrome
Caused by fluctuation in hormones during the premenstrual period, particularly the fall in oestrogen and progesterone associated with the corpus luteum degenerating prior to menstruation.
What are the features of pre-menstrual syndrome
- Bloating
- Headaches
- Backaches
- Anxiety
- Low mood
- Irritability
- symptoms improve with the onset of the menstruation.
- not present before menarche, during pregnancy or after menopause.
What is premenstrual dysphoric disorder.
features of PMS are severe and have a significant effect on quality of life
What is the management of pre-menstrual syndrome
- symptom diary relating to the menstrual cycle.
- General healthy lifestyle changes (e.g. diet, exercise, alcohol, stress, sleep etc)
- Combined contraceptive pill
- SSRIs
What is premature ovarian failure
- Defined as menopause before the age of 40 years.
- Hormonal analysis will reveal raised LH and FSH levels.
What are the causes of premature ovarian failure
- Idiopathic
- Chemotherapy
- Radiotherapy
- Autoimmune
- Turners Syndrome
What are peri-menopausal symptoms
Hot flushes Emotional lability Premenstrual syndrome Irregular periods Heavier or lighter periods Vaginal dryness Reduced libido
How are peri-menopausal symptoms managed
- Hormone Replacement Therapy: Tibolone (only when 12 months period free)
- SSRIs (e.g. fluoxetine / citalopram)
- Clonidine (act as agonists of alpha adrenergic and imidazoline receptors). Side effects are dizziness and dry mouth.
- Cognitive Behavioural Therapy
When can menopause be diagnosed
- 12 months after the last menstrual period.
- Caused by a drop in oestrogen and progesterone.
What advice regarding contraception is given to patients with the menopause
- recommended for 2 years after the last mensural period
- women under 50, and 1 year in women over 50.
What would LH/FSH hormones show in the menopause
LH and FSH are usually high, in response to the drop in the gonadal hormones.
What non-hormonal treatments are available to woman going through the menopause
General lifestyle advice (diet, exercise, weight loss, less alcohol, less caffeine, less stress etc)
SSRIs (e.g. fluoxetine)
Venlafaxine (selective serotonin-norepinephrine reuptake inhibitor)
Clonidine (alpha-2 agonist)
What types of HRT are there
- Combined oestrogen + progesterone
- Progesterone only
- Cyclical
- Continuous
- Systemic
- Local
Who should get given cyclical treatment
Peri-menopausal
Who should get given continuous treatment
post menopausal
Who should get local vs systemic HRT
Local symptoms – give topical treatment (i.e. topical oestrogen cream)
Systemic symptoms – give systemic treatment
Who should get given combined vs progesterone only
Has uterus – add progesterone
No uterus – don’t add progesterone
What are the side effects of HRT
Bloating
Breast swelling and tenderness
Weight gain
Headaches
What are the benefits of HRT
Reduces symptoms of menopause
Reduces osteoporosis
What are the downsides of HRT
- Increases risk of breast and endometrial cancer
- Increases risk of stroke and thrombosis (and coronary artery disease in longer use)
- These risks increase with longer duration of use
Why do we combine progesterone with oestrogen
- lower risk of endometrial cancer (unopposed oestrogen).
- increases the risk of breast cancer.
- No need to combine with progesterone when there is hysterectomy in past.
- mirena coil can be used to provide the progesterone component of combined HRT.
