Gynecological endocrinology

1) Polycystic ovarian syndrome (PCOS)

Α) Definition of the term – Symptoms

Polycystic ovarian syndrome, one of the most common endocrine disorders among women, has a diverse range of causes and of symptoms, the symptoms often presenting as menstrual disorders, anovulation, the presence of multiple small cysts in the ovaries, infertility / subfertility, obesity, hirsutism, alopecia, acme, and others

A patient who has PCOS will not, of course, necessarily present all the abovementioned symptoms, each individual manifesting a different group of symptoms according to the level of hormonal damage.  The scientific community, in its endeavour to define the syndrome, relies on the criteria of clinical or biochemical tests showing hyperandrogenism (increased androgens), disrupted ovulation and the presence of multiple small cysts in the ovaries.

It is important to underline that the patient who, via ultrasound, presents cysts in the ovaries, does not necessarily have PCOS, while the patient in whom no ovarian cysts are found via ultrasound may indeed have PCOS. In summary, the definitions “polycystic ovaries” and “polycystic ovarian syndrome” are not identical nor do the conditions have the same consequences for the woman.

Β) Aetiology – Investigation

The above symptoms are of endocrinological aetiology, since they involve the disruption of women’s hormones, such as insulin, the androgens, pituitary hormones, hormones of the hypothalamus in the brain, and others.

Because the aetiology of this hormonal disruption is multifaceted, the endocrinologist is called upon to determine the level / stage in the woman’s hormone metabolism at which the damage appears by applying the appropriate measurements and tests.

C) Consequences / Sequelae of the syndrome

As mentioned, the terms “polycystic ovaries” and “polycystic ovarian syndrome” are not identical nor do they have the same impact in different women.

A woman with PCOS will suffer effects involving decreased fertility, endometrial cancer, increased risk of developing metabolic diseases such as diabetes mellitus, obesity, hyperlipidaemia, gestational diabetes, cardiovascular disease, as well as clinical symptoms stemming from elevated androgens as for instance hirsutism (increased hair growth on the body) and acne.  There are also indications that women with PCOS have increased risk of miscarriage during pregnancy depending on the patient’s weight. Also important to note is the fact that PCOS increases the risk of obesity and diabetes mellitus for the unborn child later in life.

D) Treatment

Treatment of PCOS is individualized in accordance with the patient’s symptoms, since, as mentioned above, the array of symptoms is very diverse.

The basis of all treatment is diet and exercise, irrespective of body weight, since these considerably ameliorate insulin resistance and contribute to prevention of increased risk of diabetes mellitus.  They of course also help in controlling body weight and in limiting elevated adipose tissue, improving blood lipids, boosting fertility and reducing hirsutism.

Medication varies in accordance with the predominant symptom and will be focused on control of hirsutism and acne, on normalization of menstrual flow and on improving fertility and ovulation.  Much care is given to control of body weight, limitation of increased adipose tissue and reduction of blood lipids.

2) Disruption in menstrual flow

Secondary amenorrhoea means the absence of menstrual periods for over 6 months; it may be due to a number of causes, mainly hormonal.  That is to say, women who had their period but in whom it stopped more than 6 months previously have secondary amenorrhoea.

Causes

  • Pregnancy, menopause, breastfeeding / lactation
  • Iatrogenic causes (surgical removal of the uterus or ovaries, chemotherapy, radiation treatment)
  • Obstructive causes (congenital atresia of the hymen, obstruction of the vagina, the cervix, congenital or acquired cervical stenosis)
  • Problems of the central nervous system (psychogenic, psychotropic drugs, brain tumours, familial disorders, Chiari-Frommel syndrome, Laurence Moon Biedl syndrome, pituitary adenomas, prolactinaemia, Sheehan’s syndrome, Simmond’s disease)
  • Ovarian causes (dysgenesis, androgenizing tumours, other feminizing tumours, pelvic tumours, PCOS)
  • Uterus, vagina problems (congenital aplasia, Asherman’s syndrome, acquired atrophy of ovary and fallopian tube)
  • Adrenal causes (tumours, hyperplasia, Cushing’s syndrome, Addison’s disease, adrenogenital syndrome)
  • Thyroid causes (severe hyper- or hypothyoridism)
  • Obesity, eating disorders

At younger ages, the most common causes of amenorrhoea are:

  • PCOS.  The general picture of this disorder is one of a syndrome manifesting with a combination of symptoms, such as excessive hair growth, acne, delay of menstrual periods (araiomenorrhoea), absence of menstrual periods (amenorrhoea), many cysts in the ovaries
  • Much reduced body weight. Eating disorders lead to amenorrhoea, this due to the energy needs of the body not being adequately covered so that menstrual flow cannot take place. It is essential that the young person’s body fat correspond to at least 20% of total body weight in order for normal menses to be sustained.
  • Disorders of the thyroid gland can also lead to amenorrhoea or, by contrast, to excessive menstrual bleeding.
  • Excessive exercise or professional athletics.  Amenorrhoea among female athletes occurs because of hormonal imbalances (lower levels of oestrogen, because of intense exercise and very low body weight) and menstrual irregularities / irregular periods, which condition is however reversible; i.e. with the cessation of the excessive exercise, the menstrual period returns to normal.
  • Malfunctioning of the pituitary hormones
  • Unwanted pregnancies

Management depends on the cause of the problem.  The endocrinologist investigates the level of hormonal disturbance and, in accordance, recommends medication, while the gynaecologist investigates morphological causes in the uterus and the ovaries, such as obstructions, tumours, aplasias.

3) Contraception

Contraception is the use of one or more practices, preparations or medicines whose aim is the prevention or reduction of the probability of conception / pregnancy.  Methods of abstinence (a couple’s avoidance of sexual activity / intercourse on fertile days) comprise totally natural means of contraception without any side effects, though the results are very poor and there is a high rate of failure.  Both the ‘basic body temperature method’ and the ‘calendar method’, or ‘rhythm method’, are difficult to apply (e.g. the woman may be running a temperature, some women have irregular cycles, etc.). The ‘coitus interruptus’ (or ‘withdrawal’ or ‘pull-out’) method means the withdrawal of the penis from the vagina before ejaculation. It should however be noted that pre-ejaculate or pre-seminal fluid, whose purpose is to lubricate the vagina before the sexual act, may contain up to 50,000 spermatozoa

Calculation of fertile days is yet another natural method. The calculation is made in the knowledge that ovulation takes place in the middle of the 28-day cycle; that is to say that the 14th day is considered as the most fertile day of the cycle.  Considering that spermatozoa can survive in the woman’s genitalia for 30-48 hours and the egg lives about 20-30 hours after ovulation, the two days that both precede and follow ovulation are also regarded as potentially fertile, i.e. a total of five (5) days.  For greater safety, one can calculate that day 14 ± 3, which makes a total of seven (7) days.

A condom blocks the sperm, thus preventing it from entering the inside of the vagina where it could reach an egg. The risk of the condom’s rupturing (ripping or tearing) is at about 3%; this can be because of friction, poor quality, incorrect placement or that it used beyond expiry date.

Spermicides are chemicals that immobilize the sperm inside the vagina.  They are available mainly in the form of vaginal cream or foam or as vaginal pessaries. The advantages of the use of vaginal methods are that they are safe and can be applied by any woman and because they are entirely controllable by the woman. They should not however be used by young fertile women.

Intra-Uterine Devices (IUD)

These devices, made of a soft plastic or copper material, are placed by the physician in the uterus to prevent the implantation of a fertilized egg. Their use is mainly confined to women who have already born a child; women who have not yet given birth are usually not advised to use them. Advantages of IUDs are their long-term anti-contraceptive action (for 5 years) and the fact that the woman does not need during those years to constantly think about birth control protection. It is placed easily in the doctor’s office with a local anaesthetic. Before placement, the following conditions must be ruled out: pregnancy and cervical, uterine or ovarian cancer; also congenital abnormalities of the uterus and large fibroids (benign tumours of the uterus).

Oral contraceptives

Oral contraceptives, contraceptive pills or birth control pills (‘the pill’) are the oldest and most popular form of hormonal contraception, having been used for nearly half a century now.  A large number of studies have been carried out on millions of women and the view that the use of ‘the pill’ is associated with breast cancer has been disproven.  When these pills are taken in the correct way, they are capable of up to almost 100% effectiveness. Moreover, they also possess, apart from their contraceptive action, an array of additional advantages such as: improvement of acne, of unwanted hair growth, of period pains and of excessive menstrual blood loss.  They reduce the risk of benign breast conditions, endometrium, ovarian and bowel cancer and of the manifestation of ovarian cysts. A reduction in development of salpingitis (inflammation of the fallopian tubes) and of ectopic pregnancies has also been demonstrated, while they moreover prevent osteoporosis in some adolescents.

There are, of course, certain conditions and cases when women are not advised to take contraceptives: these include when women are heavy smokers and/or have haematological problems, a history of thromboses, migraine headaches, etc.  It is thus essential that before a woman starts taking contraceptives she should visit a specialist so that the above be ruled out.  Hormonal contraception exists apart from in the pill form also in other modes, including the injectable form, implants, transdermal contraceptive patch and vaginal contraceptive ring.  In any case, there are contraceptive pills with different hormones contents and the choice of the most suitable ‘cocktail’ of hormone-contraceptives will involve a study of the woman’s metabolic profile.

Τhe morning-after pill

This pill prevents the implantation in the uterus of the fertilized egg, since it alters the lining of the endometrium, while it is also believed that it may inhibit ovulation. The morning-after pill (“emergency contraceptive”) comprises an occasional, emergency method of contraception that prevents a pregnancy after a sexual contact that took place either with or without adequate protection. It can be employed when a woman has forgotten to take her “pill” or else if the condom has come off or broken; also when, during coitus interruptus, the partner has not withdrawn his penis in good time.  The morning-after pill cannot be used as a regular contraceptive method but must be applied only on the specialist’s recommendation.

4) Hormone replacement

The end of the woman’s reproductive age, which occurs roughly one year and more after the cessation of the monthly menstrual cycle, arrives any time between the ages of 45-55.  This marks the end of a gradual depletion of ovarian eggs, a process that may have begun up to 10 years previously. The drop in hormone levels in the blood has a significant impact on the female body which requires a specific hormonal environment.  Symptoms arise, such as hot flashes, insomnia, night sweats, mood swings, fatigue, loss of sexual desire, vaginal dryness, urinary incontinence, weight gain and osteoporosis. These may last for a period of up to 10 years, though this varies greatly from woman to woman.

In order to address these symptoms and to achieve a smoother transition from the pre-menopause to post-menopause condition, hormone replacement medications are often used.  The treatment involves the exogenous administration of hormones for a few years similar to those produced by the body but at smaller doses.

Choice of the optimal hormone replacement medication and the benefits of hormone replacement therapy (HRT)

There are various forms of HRT preparations, the choice of which is made by the endocrinologist as appropriate for each patient.  Taken into consideration are the following:  hysterectomy, smoking, age, cardiovascular risks, family and personal medical history, metabolic profile.  Hormone replacement is primarily administered for the control of subjective symptoms and, by extension, to improve quality of life.   Hot flashes, insomnia and night sweats are the most common reasons for which women have hormone replacement. Others are intense feeling of fatigue, mood swings and/or persistent depression. Vaginal oestrogen creams may be used when the main symptom is vaginal dryness and subsequent discomfort during sex.

The most important medical benefit of HRT is lowering the fracture risk of osteoporosis, i.e. the gradual loss of bone mass over time that can lead to fractures.  It has been established that the use of HRT can reduce the risk of fractures by 30%.

Risks involved in HRT

The use of hormone replacement has been studied extensively with regard to potential side effects, and in particular concerning an increased risk of gynaecologic cancer.  On the whole, the findings have been reassuring when the treatment is limited to no more than 5 years.

  • It does not increase the risk of uterine / endometrial cancer provided that the right hormone combination medication is chosen that contains a combination of oestrogen and progesterone.
  • It may cause a very slight increase in the potential for ovarian cancer. Over a 5-year period of use, this increase corresponds to just one additional case of ovarian cancer per 2,500 women.
  • It has been implicated in an increase in breast cancer, resulting in about 5-20 additional cases per 1,000 women who have been on medication for 10 consecutive years. The risk differs according to the type of hormone, with those preparations containing only oestrogen being considered safer.
  • It was once thought to increase the risk of heart attacks and strokes. However, newer data indicate the opposite, though the picture is as yet not perfectly clear.

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Images

Acne because of hyperandrogenism in

a woman with polycystic ovary syndrome

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Acne and increased hair growth because of hyperandrogenism

in polycystic ovary syndrome

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Increased facial hair because of hyperandrogenism

in polycystic ovary syndrome

Increased hair growth on the abdomen

in polycystic ovary syndrome