A detailed history and examination of all systems is required.
Tests of gonadal function
The patient and partner are their own best assay for gonadal endocrine function. A man having regular satisfactory intercourse or a woman with regular ovulatory periods is most unlikely to have significant endocrine disease, assuming the history is accurate (check with the partner!). When symptoms are present, much can be deduced by basal measurements of the gonadotrophins, oestrogens/ testosterone and prolactin:
Low TESTOSTERONE OR OESTRADIOL WITH HIGH GO ADOTROPHINS indicates primary gonadal disease.
Low LEVELS OF LH/FSH AND TESTOSTERONE/OESTRADI0L imply hypothalamic-pituitary disease.
CONFIRMATION OF NORMAL FEMALE REPRODUCTIVE ENDOCRINOLOGY requires the demonstration of ovulation-this is achieved by measurement of luteal phase serum progesterone and/or by serial ovarian ultrasound in the follicular phase.
COMPLETE DEMONSTRATION OF NORMAL MALE AND FEMALE FUNCTION requires a pregnancy-in the male, in the first instance there should be a healthy sperm count (20-200 X 106/ml), good motility (>60% Grade 1) and few abnormal forms «20%).
HYPERPROLACTINAEM IA can be confirmed or excluded by direct measurement of preferably two to three samples. Levels may increase with stress; ideally, a cannula should be inserted and samples taken through it 30 min later.
THE CLOMIPHENE TEST examines hypothalamic negative feedback. Clomiphene is a competitive oestrogen antagonist that binds to, but does not activate, oestrogen receptors, thus inducing a rise in gonadotrophin secretion in the normal subject. More detailed tests are indicated.
Tests of gonadal function.
DISORDERS IN THE MALE
Male hypogonadism may be a presenting complaint or an incidental finding, e.g. during investigation for subfertility. The testes may be small and soft. Except with sub fertility, the complaints are usually of androgen deficiency rather than deficiency of semen production. Sperm only makes up a very small proportion of seminal fluid volume. Causes of male hypogonadism.
Maintenance of libido
Deepening of voice
Facial, axillary and limb hair
Maintenance of male pattern
Testes and scrotum
Maintenance of testicular size/consistency
Rugosity of scrotum
Maintenance of erectile and ejaculatory function
Stimulation of spermatogenesis
Maintenance of muscle bulk
Testicular disease may be initially apparent but basal levels of testosterone, LH and FSH should be measured. These will allow the distinction between primary gonadal (testicular) failure and hypothalamic-pituitary disease to be made. Biopsy of the testes may be indicated, though rarely yields a treatable cause. Skull radiology, pituitary CT scan, prolactin levels and other pituitary function tests may be needed. Depending on the causes, semen analysis, chromosomal analysis (e.g. to exclude Klinefelter’s syndrome) and bone age estimation may be required.
The cause can rarely be reversed. Replacement therapy should be commenced. Primary gonadal failure should be treated with androgens. Patients with hypothalamic-pituitary disease may be given LH and FSH (Pergonal) or pulsatile LHRH if fertility is required, otherwise they should receive androgen replacement. Special instances of hypogonadism include:
CRYPTORCHIDISM. By the age of 5 years both testes should be in the scrotum. After that age the germinal epithelium is increasingly at risk; lack of descent by puberty is associated with infertility. Surgical exploration and orchidopexy are usually undertaken but a short trial of HCG occasionally induces descent: an HCG test with a testosterone response 72 hours later excludes anorchia. Intra-abdominal testes have an increased risk of developing malignancy; if presentation is after puberty, orchidectomy is advised.
KLINEFELTER’S SY DROME (seminiferous tubule dysgenesis). This chromosomal disorder (47XXY) affecting 1 in 1000 males involves loss of both Leydig cells and seminiferous tubular dysgenesis. Patients usually present with poor sexual development, small or undescended testes, gynaecomastia or infertility. They are sometimes mentally retarded. Clinical examination shows small pea-size but firm testes, usually gynaecomastia and often signs of androgen deficiency. Confirmation is by chromosomal analysis. Treatment is androgen replacement therapy, though if the patient is mentally subnormal this should be used carefully. No treatment is possible for the abnormal seminiferous tubules and infertility.
Androgen replacement therapy.
ISOLATED DEFICIENCY OF LHRH OR LH/FSH
(Kallmann’s syndrome). Also known as hypogonadotrophic hypogonadism, this is often associated with decreased sense of smell (anosmia), and sometimes with other bony (cleft-palate), renal and cerebral abnormalities (e.g. colour blindness). It is often familial and is usually X-linked; the genetic defect has recently been identified. Management is that of secondary hypogonadism; fertility is possible.
OLIGOSPERMIA OR AZOOSPERMIA. These may be secondary to androgen deficiency and corrected by replacement but more often they result from primary testicular diseases in which case they are rarely treatable.
AZOOSPERMIA WITH NORMAL TESTICULAR SIZE AND LOW FSH LEVELS suggests a vas deferens block.
Lack of libido and impotence
Many patients with impotence have no definable organic cause. A careful history of physical disease, related symptoms, stress and psychological factors, together with drug and alcohol abuse, must be taken. The presence of nocturnal emissions and frequent satisfactory morning erections largely excludes endocrine disease as a cause. True erectile difficulty may be psychological, neurogenic, vascular, endocrine or related to drugs. Vascular disease may be more common than realized and is often associated with vascular problems elsewhere. The endocrine causes are those of hypogonadism (above) and can be excluded by normal testosterone, gonadotrophin and prolactin levels. Autonomic neuropathy, most commonly from diabetes mellitus, is a common partial, if not total, identifiable cause. Many drugs can be responsible-cannabis, diuretics, metoclopramide, bethanidine/guanethidine, methyldopa and f3-blockers all produce impotence. Psychogenic impotence is frequently a diagnosis of exclusion, though complex tests of penile vasculature and function are now available in some centres. Apart from cessation of the offending drug, methods of treatment include vacuum condoms, intracavernosal injections of papaverine and phentolamine, penile implants and vacuum expanders; specialist advice is essential.
If no organic disease is found, or if there is clear evidence of psychological problems, the couple should receive psychosexual counselling.
Gynaecomastia is development of breast tissue in the male.
Pubertal gynaecomastia occurs in perhaps 50% of normal boys, often asymmetrically. It usually resolves spontaneously within 6-18 months but after this duration may require surgical removal, as fibrous tissue will have been laid down. The cause is thought to be relative oestrogen excess.
In the older male, gynaecomastia requires a full assessment to exclude potentially serious underlying disease, such as bronchial carcinoma and testicular turn ours (e.g. Leydig cell tumour). Drug effects are common (especially digoxin and spironolactone) and once these are excluded most cases have no definable cause. Surgical removal is occasionally necessary.
Oestrogen-producing tumours (testis. adrenal)
HCG-producing tumours (testis. lung)
Carcinoma of breast
DISORDERS IN THE FEMALE
Impaired ovarian function, whether primary or secondary, will lead both to oestrogen deficiency and abnormalities of the menstrual cycle. The latter is very sensitive to disruption, cycles becoming anovulatory and irregular before disappearing altogether. Symptoms will depend on the age at which the failure develops. Thus, before puberty, primary amenorrhoea will occur, possibly with delayed puberty; if after puberty, secondary amenorrhoea and possibly hypogonadism will result. Oestrogen deficiency The physiological effects of oestrogins and symptomsl signs of deficiency.
Absence of periods or markeclly irregular infrequent periods (oligomenorrhoea) are a common presentation, often the earliest, of female gonadal disease. Important factors in clinical assessment of such patients.
Effects of oestrogens and consequences of
factors in clinical assessment of such patients.
PREGNANCY. This must a/wars be considered.
GENITAL TRACT ABNORMALITIES, such as imperforate hymen, should be remembered, especially in primary amenorrhoea.
WEIGHT-RELATED AMENORRHOEA. A minimum body weight is necessary for regular menstruation. While anorexia nervosa is the extreme form, this condition is common and may be seen at weights within the ‘normal’ range. Many of these subjects may have additional minor endocrine disease (e.g. polycystic ovarian disease) but restoration of body weight toabove the 50th centile is often helpful. Similar problems occur with intensive physical training in athletes and dancers.
HYPOTHALAMIC AMENORRHOEA. Some dispute the existence of this condition, linking all amenorrhoea to low weight or increased stress. A few patients, however, do appear to have defective cycling mechanisms without apparent explanation.
HYPOTHYROIDISM results in increased TRH which timulates prolactin secretion.
SEVERE ILL ESS, even in the absence of weight loss.
AFTER STOPPING THE CONTRACEPTIVE PILL.
Age of onset
Age of menarche, if any
Sudden or gradual onset
Weight, absolute and changes in recent past
Stress Gob, life-style, exams, relationships)
Hirsuties, acne, virilization
Sense of smell
Past history of pregnancies
Past history of gynaecological surgery
Body shape and skeletal abnormalities
Weight and height
Hirsuties and acne
Evidence of virilization
Maturity of secondary sexual characteristics
Normality of vagina, cervix and uterus
Basal levels of FSH, LH, oestrogen and prolactin allow initial distinction between primary gonadal and hypothalamic- pituitary causes (Table 16.17). Ovarian biopsy is necessary to confirm the diagnosis of primary ovarian failure. Subsequent investigations.
Treatment is that of the cause wherever possible (e.g. hypothyroidism, low weight, stress, excessive exercise). Primary ovarian disease is rarely treatable except in the rare condition of ‘resistant’ ovary, where high-dose Pergonal can occasionally lead to folliculogenesis. Hyperprolactinaemia should be corrected. Polycystic ovarian syndrome is discussed in detail below.