Tagcloud

abortion, accupuncture, ACE inhibitors, acne, ADHD, alcohol, allergies, Alzheimer's, anaemia, anaethesia, anorexia, antibiotics, antidepressants, antihistamine, anxiety, appetite control, arthritis, ASCOT, aspirin, asthma, atherosclerosis, autism, autoantibodies, back pain, beta carotene, beta-blockers, bipolar disorder, birth, bleeding, blindness, blood pressure, body dysmorphic disorder, body mass, breast cancer, breast feeding, bronchitis, Caesarean section, calcium, cancer, carcinogens, carcinoma, cardiac syncope, cardiolgy, cataracts, cervical cancer, chemotherapy, child psychiatry, children, cholesterol, clinical trial, clopidogrel, Clostridium difficile, cognitive behavioural therapy, colectomy, colic, colorectal cancer, complementary and alternative therapies, contraception, COPD, coronary care, coronary stents, Crohn's, cystic fibrosis, defibrillator, dementia, depression, dermatology, diabetes management, diet, disability, DNA, Down's syndrome, eating disorders, echinacea, ECT, eczema, elderly people, endoscopy, epilepsy, erectile dysfunction, euthanasia, exercise, fat, fertility, fitness, flu pandemic, fluoxetine, folic acid, food labelling, fracture, fragile X syndrome, general surgery, genetics, gerontology, GIK infusion therapy, GORD, gout, haemodialysis, hearing, heart attack, heart disease, heart failure, heart health, hepatitis, HIV, hospital care, HPV, HRT, hyperglycaemia, hypertension, hypoglycaemia, IBD, ICU, incontinence, infant, infant mortality, infection, inflammatory bowel disease, influenza, invasive candidiasis, IQ, Irish Heart Foundation, irritable bowel syndrome, keyhole surgery, kidney disease, laser, learning difficulties, leukaemia, liver disease, lumbar disk herniation, lung cancer, lung disease, lymph nodes, macular degeneration, macular oedema, magnetic resonance imaging (MRI), malaria, malnutrition, Marfan syndrome, media, medical ethics, medical research, medication, meningitis, mental health, mental illness, metabolic syndrome, migraine, miscarriage, mortality rate, MRSA, multiple sclerosis (MS), NCHDs, nephrology, neurology, OAB, obesity, obstetrics, occupational health, ocular medicine, omega-3, opthalmology, oral cancer, organ transplantation, orthopaedics, osteoporosis, otolaryngology, ovarian cancer, paediatrics, pain management, pancreatic cancer, panic, Parkinson’s disease, patient safety, patient-physician communication, personality disorders, physiotherapy, plastic surgery, polio, practice, pre-eclampsia, pregnancy, preventative health care, probiotics, prostate cancer, psoriasis, psychiatric admission, psychiatry, psychotherapy, PTSD, public health, quality of life, radiology, radiotherapy, rectal cancer, reproductive health, research, resuscitation, rheumatoid arthritis, rheumatology, rhinitis, salt, SARS, schizophrenia, screening, seizures, self harm, sexual abuse, sexual health, sexually transmitted infections, SGA, sinusitis, skin cancer, sleep disorders, smoking, smoking ban, spinal injury, sports medicine, statins, stem cells, stress, stroke, substance abuse, suicide, supplement, surgery, syncope, technology, teenagers, testosterone, thoracic surgery, thrombosis, thyroid cancer, tonsillectomy, tonsillitis, Tourette's syndrome, toxicology, travel medicine, tuberculosis, tumour angiogenesis, type 1 diabetes, type 2 diabetes, ulcer, ulcerative colitis, urinary incontinence, vaccine, vitamins, weight, WHO, women's health, World Health Assembly

«Previous article | Next article»

The Endocrinology Clinic: PCOS

Continuing their series on ‘Notes from the Endocrinology Clinic’, Dr Frances Hayes and Prof T Joseph McKenna examine polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is the commonest endocrine disorder in young women. It has recently been defined by the presence of at least two of the following: oligomenorrhoea or amenorrhoea; hyperandrogenism manifest by clinical features such as hirsutism, acne and/or elevated androgen concentrations in blood; sonographic demonstration of polycystic ovaries; and, in the absence of other causes, including Cushing’s syndrome, congenital adrenal hyperplasia and androgen-secreting benign or malignant adrenal or ovarian tumours.

The underlying mechanisms giving rise to PCOS have not been defined. There is a frequent but not necessary association with insulin resistance and obesity, although insulin resistance may be seen in PCOS patients of normal weight. As a consequence of insulin resistance, impaired glucose tolerance or diabetes mellitus may occur in up to 25 per cent of PCOS patients.

The full-blown metabolic syndrome characterised by dyslipidaemia, hypertension, obesity, varying degrees of glucose intolerance, a thrombogenic coagulation profile and the presence of markers indicative of a pro-inflammatory state, frequently accompanies PCOS.

Its aetiology has been the subject of intense research without a clear understanding emerging. Approximately 25 per cent of women in the reproductive phase of life will demonstrate polycystic ovaries (PCO) on ultrasound examination, but only about a quarter of these women develop PCOS. The development of PCO is probably congenital and there is a familial occurrence of PCO and PCOS. It is likely that PCO are necessary but not sufficient for the development of PCOS.

Associated disorders
Other associated disorders in the emergence of PCOS include insulin resistance, steroidogenic defects which render the ovaries and in many cases, the adrenals, hyper-responsive to various normal and abnormal stimuli, of which insulin may be one. There is also well-described disturbance in the normal pulsatile secretion of LH from the pituitary manifest by increased frequency and amplitude.

PCOS is by far the commonest cause of hirsutism, which affects up to 8 per cent of women. Diagnosis is likely when hirsutism presents in the decade 15 to 25 years and usually more than 12 months after first noted by the patient, indicating slow progression (See table, p41).

PCOS is usually associated with menstrual disturbance but very rarely with virilisation. Clinical diagnosis of PCOS should not be made when patients present outside these parameters. Comprehensive evaluation for other disorders should be undertaken under those circumstances.

Measurement of early morning serum 17-hydroxyprogesterone or in response to stimulation with the ACTH analogue corticotrophin (Synacthen) 250µg im, provides screening for congenital adrenal hyperplasia due to 21-hyrroxylase deficiency.

Screening for Cushing’s syndrome is accomplished by measuring morning serum cortisol following administration of dexamethasone, 1mg at midnight, when the concentration should be suppressed to less than 50-100nmol/l.

Imaging of the adrenals and ovaries is best undertaken with CT scanning and ultrasonography respectively.

Hyperandrogenaemia
While PCOS diagnosis may be made on clinical grounds, measurement of serum testosterone and possibly sex hormone binding globulin (SHBG) may be prudent to provide a baseline value against which to assess treatment response and to identify the rare occurrence of cryptic severe hyperandro-genaemia.

Serum testosterone in excess of twice the upper limit of the reference range or a free testosterone concentration/index greater than fivefold above the upper reference range should raise the possibility of a diagnosis other than PCOS and prompt additional evaluation.

A serum LH/FSH ratio of greater than two is consistent with PCOS diagnosis. Approximately 25 per cent of the general population of women will have polycystic ovaries on ultrasound examination, so this finding lacks specificity.

PCOS patients should have measurement of fasting blood glucose and serum lipids and ideally two-hour post-prandial blood glucose concentrations, particularly those who are obese or have a family history of type 2 diabetes.

PCOS treatment depends on each patient’s specific clinical presentation, goals and the findings on hormonal and biochemical screening.

The issues arising include hirsutism, acne, obesity, concerns about immediate or future fertility, impaired fasting glucose, impaired glucose tolerance, diabetes, dyslipidaemia and hypertension. The management of hirsutism will be addressed separately by the authors in a future article. Hirsutism may be treated using local cosmetic measures, topical agents to delay hair growth-rate, anovulants to suppress ovarian androgen production and anti-androgens.

Conventional acne treatment should be employed i.e. prolonged courses of broad spectrum antibiotics and anovulants. Oligomennorrhoea or amenorrhoea may be distressing because of infertility concerns and fertility regulation/inconveniences associated with unpredictability.

Prolonged amenorrhoea may be associated with an increased rate of endometrial hyperplasia/neoplasia. PCOS is an oestrogen-rich state and in the absence of regular shedding, endometrial hyperplasia occurs analogous to the effect of oestrogen-only treatment.

Regular withdrawal bleeding and suppression of ovulation will be achieved using the combination anovulants. An alternative is the use of a progestogen to induce withdrawal bleeding when spontaneous menstruation has not occurred for two-to-three months.

Medroxyprogesterone acetate has been extensively used in the management of PCOS patients in a schedule of 10mg daily for five days. This usually results in normal bleeding lasting two-to-four days commencing three-tos-ix days after the last day of treatment.

Problems associated with insulin resistance in PCOS are severalfold, giving rise to raised glucose and lipid concentrations in blood and contributing significantly to the elevated androgen levels in serum and to disruption of regular ovulation. To understand these features of insulin resistance in PCOS, it is necessary to appreciate that only some tissues demonstrate resistance, i.e. liver and muscle. To overcome insulin resistance in an attempt to return blood glucose concentrations to the physiological range, insulin levels may become markedly elevated.

Conventional wisdom has it that other tissues, e.g. skin, ovaries, retain full sensitivity to insulin. This can result in hyperplasia of dermal and epidermal cells and the development of acanthosis nigricans characterised by areas of dark raised ‘velvety’ skin, typically in the axillae and on the neck.

Raised insulin concentrations (alone or by augmenting the LH effect) stimulate androgen production from theca cells both in normal and polycystic ovaries. As a consequence of this or through another effect, raised insulin levels are also incriminated in the suppression of ovulation in PCOS. It is likely that increasing liver and muscle cell sensitivity to insulin will lower insulin concentrations in blood and achieve several therapeutic endpoints in PCOS. These endpoints include improvement in glucose and lipid profiles while lowering serum androgen levels and facilitating ovulation.

Increased insulin sensitivity can be achieved through lifestyle modification and/or pharmaceutical agents. Weight loss is effective in lowering insulin concentrations in blood, which is associated with lowering serum testosterone and increasing the frequency of menstruation and ovulation in PCOS.

For overweight patients, this is particularly helpful and as an isolated form of treatment, may be sufficient to address infertility. In other patients, introducing an insulin sensitiser may also be helpful.

In this regard, most experience has been gained with metformin, although none of these agents has an approved indication for use in PCOS.

Favourable outcomes
Several papers in medical literature over the past 10 to 15 years report extensive favourable outcomes in PCOS. These include increased ovulation and pregnancy rates, reduced miscarriage rates and reduced frequency of gestational diabetes.

The usual starting dose of metformin is 500mg twice daily, which may be increased to thrice daily or to 850mg twice daily, which has usually been discontinued in pregnancy. However, limited data suggest it may reduce miscarriages rates. Therefore in women with a history of miscarriage, metformin is sometimes continued until the end of the first trimester. Some recent studies have questioned the effectiveness of metformin in the treatment of PCOS, but the agent is still widely used.

With weight loss and/or treatment with metformin, the incidence of multiple births in PCOS patients is not increased. Where these modalities of treatment are not successful, clomiphene citrate is usually the next agent of choice.

Clomiphene citrate is an anti-oestrogen that blocks the negative feedback on FSH secretion from the pituitary. This results in a surge of FSH secretion, which may stimulate ovarian follicular development and, when successful, lead to ovulation.

Use of clomiphene citrate is usually preceded by administration of a progestogen.

Pretreatment with an agent such as medroxyprogesterone acetate tends to correct abnormalities in LH secretion and leads to shedding of the endometrium which may be hyperplastic. The resulting menstruation confirms the non-pregnant state.

Clomiphene citrate 50mg orally daily for five days is usually commenced on the fifth day of menstruation. Ovulation is most likely to occur 10-12 days after the commencement of clomiphene citrate and the patient should be advised accordingly.

When unsuccessful at the 50mg dosage, clomiphene citrate may be increased by 50mg daily for each five-day cycle up to 200mg or until ovulation has been induced for a maximum of six cycles. There is an approximately 75 per cent success rate in inducing ovulation when prescribing clomiphene citrate following this schedule, although the pregnancy rate is approximately half that.

It has been reported that this can be enhanced with the addition of metformin. Rarely, treatment may be complicated by the hyperstimulation syndrome, particularly at higher doses. There is an increased incidence of multiple births at 7 to 9 per cent.

When clomiphene citrate is unsuccessful, gonadotropin treatment should be considered. This requires daily FSH sc injection, ultrasonographic tracking of ovarian follicular development and regular oestrogen measurement to guard against the hyperstimulation syndrome, which may be life threatening. Ovulation induction employing gonadotropin treatment should be undertaken only in specialised units experienced in the techniques.

Miscarriage rate
Irrespective of the manner whereby ovulation occurs (spontaneous, following weight loss or drugs, e.g. metformin, clomiphene citrate or gonadotropin use) that results in pregnancy, the miscarriage rate is increased in women with PCOS.

It has been reported that metformin treatment reduces miscarriage in PCOS from approximately 40 per cent to 10 per cent. Metformin also has beneficial effects on various aspects of the metabolic syndrome, which is the subject of a separate contribution.

Frances Hayes* and
T Joseph McKenna**,
*Consultant Endocrinologist
Honorary Consultant,
St Vincent’s University Hospital, Elm Park, Dublin 4;
**Specialist in Endocrinology and Diabetes Mellitus,
The Mews, 1 De Vesci Terrace,
Dun Laoghaire, Co. Dublin.

Posted in Women's Health on 21 January 2010
Tags: fertility

Tagcloud

abortion, accupuncture, ACE inhibitors, acne, ADHD, alcohol, allergies, Alzheimer's, anaemia, anaethesia, anorexia, antibiotics, antidepressants, antihistamine, anxiety, appetite control, arthritis, ASCOT, aspirin, asthma, atherosclerosis, autism, autoantibodies, back pain, beta carotene, beta-blockers, bipolar disorder, birth, bleeding, blindness, blood pressure, body dysmorphic disorder, body mass, breast cancer, breast feeding, bronchitis, Caesarean section, calcium, cancer, carcinogens, carcinoma, cardiac syncope, cardiolgy, cataracts, cervical cancer, chemotherapy, child psychiatry, children, cholesterol, clinical trial, clopidogrel, Clostridium difficile, cognitive behavioural therapy, colectomy, colic, colorectal cancer, complementary and alternative therapies, contraception, COPD, coronary care, coronary stents, Crohn's, cystic fibrosis, defibrillator, dementia, depression, dermatology, diabetes management, diet, disability, DNA, Down's syndrome, eating disorders, echinacea, ECT, eczema, elderly people, endoscopy, epilepsy, erectile dysfunction, euthanasia, exercise, fat, fertility, fitness, flu pandemic, fluoxetine, folic acid, food labelling, fracture, fragile X syndrome, general surgery, genetics, gerontology, GIK infusion therapy, GORD, gout, haemodialysis, hearing, heart attack, heart disease, heart failure, heart health, hepatitis, HIV, hospital care, HPV, HRT, hyperglycaemia, hypertension, hypoglycaemia, IBD, ICU, incontinence, infant, infant mortality, infection, inflammatory bowel disease, influenza, invasive candidiasis, IQ, Irish Heart Foundation, irritable bowel syndrome, keyhole surgery, kidney disease, laser, learning difficulties, leukaemia, liver disease, lumbar disk herniation, lung cancer, lung disease, lymph nodes, macular degeneration, macular oedema, magnetic resonance imaging (MRI), malaria, malnutrition, Marfan syndrome, media, medical ethics, medical research, medication, meningitis, mental health, mental illness, metabolic syndrome, migraine, miscarriage, mortality rate, MRSA, multiple sclerosis (MS), NCHDs, nephrology, neurology, OAB, obesity, obstetrics, occupational health, ocular medicine, omega-3, opthalmology, oral cancer, organ transplantation, orthopaedics, osteoporosis, otolaryngology, ovarian cancer, paediatrics, pain management, pancreatic cancer, panic, Parkinson’s disease, patient safety, patient-physician communication, personality disorders, physiotherapy, plastic surgery, polio, practice, pre-eclampsia, pregnancy, preventative health care, probiotics, prostate cancer, psoriasis, psychiatric admission, psychiatry, psychotherapy, PTSD, public health, quality of life, radiology, radiotherapy, rectal cancer, reproductive health, research, resuscitation, rheumatoid arthritis, rheumatology, rhinitis, salt, SARS, schizophrenia, screening, seizures, self harm, sexual abuse, sexual health, sexually transmitted infections, SGA, sinusitis, skin cancer, sleep disorders, smoking, smoking ban, spinal injury, sports medicine, statins, stem cells, stress, stroke, substance abuse, suicide, supplement, surgery, syncope, technology, teenagers, testosterone, thoracic surgery, thrombosis, thyroid cancer, tonsillectomy, tonsillitis, Tourette's syndrome, toxicology, travel medicine, tuberculosis, tumour angiogenesis, type 1 diabetes, type 2 diabetes, ulcer, ulcerative colitis, urinary incontinence, vaccine, vitamins, weight, WHO, women's health, World Health Assembly

«Previous article | Next article»

The Endocrinology Clinic: PCOS

Continuing their series on ‘Notes from the Endocrinology Clinic’, Dr Frances Hayes and Prof T Joseph McKenna examine polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is the commonest endocrine disorder in young women. It has recently been defined by the presence of at least two of the following: oligomenorrhoea or amenorrhoea; hyperandrogenism manifest by clinical features such as hirsutism, acne and/or elevated androgen concentrations in blood; sonographic demonstration of polycystic ovaries; and, in the absence of other causes, including Cushing’s syndrome, congenital adrenal hyperplasia and androgen-secreting benign or malignant adrenal or ovarian tumours.

The underlying mechanisms giving rise to PCOS have not been defined. There is a frequent but not necessary association with insulin resistance and obesity, although insulin resistance may be seen in PCOS patients of normal weight. As a consequence of insulin resistance, impaired glucose tolerance or diabetes mellitus may occur in up to 25 per cent of PCOS patients.

The full-blown metabolic syndrome characterised by dyslipidaemia, hypertension, obesity, varying degrees of glucose intolerance, a thrombogenic coagulation profile and the presence of markers indicative of a pro-inflammatory state, frequently accompanies PCOS.

Its aetiology has been the subject of intense research without a clear understanding emerging. Approximately 25 per cent of women in the reproductive phase of life will demonstrate polycystic ovaries (PCO) on ultrasound examination, but only about a quarter of these women develop PCOS. The development of PCO is probably congenital and there is a familial occurrence of PCO and PCOS. It is likely that PCO are necessary but not sufficient for the development of PCOS.

Associated disorders
Other associated disorders in the emergence of PCOS include insulin resistance, steroidogenic defects which render the ovaries and in many cases, the adrenals, hyper-responsive to various normal and abnormal stimuli, of which insulin may be one. There is also well-described disturbance in the normal pulsatile secretion of LH from the pituitary manifest by increased frequency and amplitude.

PCOS is by far the commonest cause of hirsutism, which affects up to 8 per cent of women. Diagnosis is likely when hirsutism presents in the decade 15 to 25 years and usually more than 12 months after first noted by the patient, indicating slow progression (See table, p41).

PCOS is usually associated with menstrual disturbance but very rarely with virilisation. Clinical diagnosis of PCOS should not be made when patients present outside these parameters. Comprehensive evaluation for other disorders should be undertaken under those circumstances.

Measurement of early morning serum 17-hydroxyprogesterone or in response to stimulation with the ACTH analogue corticotrophin (Synacthen) 250µg im, provides screening for congenital adrenal hyperplasia due to 21-hyrroxylase deficiency.

Screening for Cushing’s syndrome is accomplished by measuring morning serum cortisol following administration of dexamethasone, 1mg at midnight, when the concentration should be suppressed to less than 50-100nmol/l.

Imaging of the adrenals and ovaries is best undertaken with CT scanning and ultrasonography respectively.

Hyperandrogenaemia
While PCOS diagnosis may be made on clinical grounds, measurement of serum testosterone and possibly sex hormone binding globulin (SHBG) may be prudent to provide a baseline value against which to assess treatment response and to identify the rare occurrence of cryptic severe hyperandro-genaemia.

Serum testosterone in excess of twice the upper limit of the reference range or a free testosterone concentration/index greater than fivefold above the upper reference range should raise the possibility of a diagnosis other than PCOS and prompt additional evaluation.

A serum LH/FSH ratio of greater than two is consistent with PCOS diagnosis. Approximately 25 per cent of the general population of women will have polycystic ovaries on ultrasound examination, so this finding lacks specificity.

PCOS patients should have measurement of fasting blood glucose and serum lipids and ideally two-hour post-prandial blood glucose concentrations, particularly those who are obese or have a family history of type 2 diabetes.

PCOS treatment depends on each patient’s specific clinical presentation, goals and the findings on hormonal and biochemical screening.

The issues arising include hirsutism, acne, obesity, concerns about immediate or future fertility, impaired fasting glucose, impaired glucose tolerance, diabetes, dyslipidaemia and hypertension. The management of hirsutism will be addressed separately by the authors in a future article. Hirsutism may be treated using local cosmetic measures, topical agents to delay hair growth-rate, anovulants to suppress ovarian androgen production and anti-androgens.

Conventional acne treatment should be employed i.e. prolonged courses of broad spectrum antibiotics and anovulants. Oligomennorrhoea or amenorrhoea may be distressing because of infertility concerns and fertility regulation/inconveniences associated with unpredictability.

Prolonged amenorrhoea may be associated with an increased rate of endometrial hyperplasia/neoplasia. PCOS is an oestrogen-rich state and in the absence of regular shedding, endometrial hyperplasia occurs analogous to the effect of oestrogen-only treatment.

Regular withdrawal bleeding and suppression of ovulation will be achieved using the combination anovulants. An alternative is the use of a progestogen to induce withdrawal bleeding when spontaneous menstruation has not occurred for two-to-three months.

Medroxyprogesterone acetate has been extensively used in the management of PCOS patients in a schedule of 10mg daily for five days. This usually results in normal bleeding lasting two-to-four days commencing three-tos-ix days after the last day of treatment.

Problems associated with insulin resistance in PCOS are severalfold, giving rise to raised glucose and lipid concentrations in blood and contributing significantly to the elevated androgen levels in serum and to disruption of regular ovulation. To understand these features of insulin resistance in PCOS, it is necessary to appreciate that only some tissues demonstrate resistance, i.e. liver and muscle. To overcome insulin resistance in an attempt to return blood glucose concentrations to the physiological range, insulin levels may become markedly elevated.

Conventional wisdom has it that other tissues, e.g. skin, ovaries, retain full sensitivity to insulin. This can result in hyperplasia of dermal and epidermal cells and the development of acanthosis nigricans characterised by areas of dark raised ‘velvety’ skin, typically in the axillae and on the neck.

Raised insulin concentrations (alone or by augmenting the LH effect) stimulate androgen production from theca cells both in normal and polycystic ovaries. As a consequence of this or through another effect, raised insulin levels are also incriminated in the suppression of ovulation in PCOS. It is likely that increasing liver and muscle cell sensitivity to insulin will lower insulin concentrations in blood and achieve several therapeutic endpoints in PCOS. These endpoints include improvement in glucose and lipid profiles while lowering serum androgen levels and facilitating ovulation.

Increased insulin sensitivity can be achieved through lifestyle modification and/or pharmaceutical agents. Weight loss is effective in lowering insulin concentrations in blood, which is associated with lowering serum testosterone and increasing the frequency of menstruation and ovulation in PCOS.

For overweight patients, this is particularly helpful and as an isolated form of treatment, may be sufficient to address infertility. In other patients, introducing an insulin sensitiser may also be helpful.

In this regard, most experience has been gained with metformin, although none of these agents has an approved indication for use in PCOS.

Favourable outcomes
Several papers in medical literature over the past 10 to 15 years report extensive favourable outcomes in PCOS. These include increased ovulation and pregnancy rates, reduced miscarriage rates and reduced frequency of gestational diabetes.

The usual starting dose of metformin is 500mg twice daily, which may be increased to thrice daily or to 850mg twice daily, which has usually been discontinued in pregnancy. However, limited data suggest it may reduce miscarriages rates. Therefore in women with a history of miscarriage, metformin is sometimes continued until the end of the first trimester. Some recent studies have questioned the effectiveness of metformin in the treatment of PCOS, but the agent is still widely used.

With weight loss and/or treatment with metformin, the incidence of multiple births in PCOS patients is not increased. Where these modalities of treatment are not successful, clomiphene citrate is usually the next agent of choice.

Clomiphene citrate is an anti-oestrogen that blocks the negative feedback on FSH secretion from the pituitary. This results in a surge of FSH secretion, which may stimulate ovarian follicular development and, when successful, lead to ovulation.

Use of clomiphene citrate is usually preceded by administration of a progestogen.

Pretreatment with an agent such as medroxyprogesterone acetate tends to correct abnormalities in LH secretion and leads to shedding of the endometrium which may be hyperplastic. The resulting menstruation confirms the non-pregnant state.

Clomiphene citrate 50mg orally daily for five days is usually commenced on the fifth day of menstruation. Ovulation is most likely to occur 10-12 days after the commencement of clomiphene citrate and the patient should be advised accordingly.

When unsuccessful at the 50mg dosage, clomiphene citrate may be increased by 50mg daily for each five-day cycle up to 200mg or until ovulation has been induced for a maximum of six cycles. There is an approximately 75 per cent success rate in inducing ovulation when prescribing clomiphene citrate following this schedule, although the pregnancy rate is approximately half that.

It has been reported that this can be enhanced with the addition of metformin. Rarely, treatment may be complicated by the hyperstimulation syndrome, particularly at higher doses. There is an increased incidence of multiple births at 7 to 9 per cent.

When clomiphene citrate is unsuccessful, gonadotropin treatment should be considered. This requires daily FSH sc injection, ultrasonographic tracking of ovarian follicular development and regular oestrogen measurement to guard against the hyperstimulation syndrome, which may be life threatening. Ovulation induction employing gonadotropin treatment should be undertaken only in specialised units experienced in the techniques.

Miscarriage rate
Irrespective of the manner whereby ovulation occurs (spontaneous, following weight loss or drugs, e.g. metformin, clomiphene citrate or gonadotropin use) that results in pregnancy, the miscarriage rate is increased in women with PCOS.

It has been reported that metformin treatment reduces miscarriage in PCOS from approximately 40 per cent to 10 per cent. Metformin also has beneficial effects on various aspects of the metabolic syndrome, which is the subject of a separate contribution.

Frances Hayes* and
T Joseph McKenna**,
*Consultant Endocrinologist
Honorary Consultant,
St Vincent’s University Hospital, Elm Park, Dublin 4;
**Specialist in Endocrinology and Diabetes Mellitus,
The Mews, 1 De Vesci Terrace,
Dun Laoghaire, Co. Dublin.

Posted in Women's Health on 21 January 2010
Tags: fertility