What Are Hormones?

Hormones are chemical messengers in the body that instruct its own dedicated target cells what to do.

Examples of hormone producing glands in the body, related to fertility are:

The pituitary gland at the base of the brain, and the adjacent area inside the brain called the hypothalamus

• The ovaries in a woman
• The testicles in a man

There are many more glands in the body that produce hormones such as the thyroid gland in the neck, producing thyroxine which regulates the general metabolism. This is not a hormone that belongs to the reproductive system, but abnormalities in the levels of the thyroid hormones can disturb the normal functioning of the body and indirectly affect the reproductive organs.

Hormones can be very small (such as the thyroid hormones), intermediate size, such as the steroid hormones oestrogen and testosterone, or very large such as the peptide hormones, of which Follicle stimulating hormone and Luteinizing hormone are examples.

Hormones are produced in glands, and are then released into bodily fluids, like blood, which carry them to target cells, either directly adjacent, or far away in the body.

Target cells only will respond to a hormone when they have a specific receptor for that hormone, and when this hormone receptor gets activated by the incoming and binding hormone, the cells will then respond by carrying out a specific function such as production of other hormones, or starting a new process, such as growing an egg on the ovary, or production of spermatozoa in the testicles.

Regulation of the reproductive system is a process that requires the action and reaction of hormones from the hypothalamus, the pituitary gland, and the gonads (ovaries and testicles), with constant communication between the hormone producing organs (glands) and their target cells so that the levels of all the important hormones do not go too high or too low (“balanced” hormone levels).

During puberty, in both males and females, the hypothalamus produces gonadotropin-releasing hormone (GnRH), which stimulates the production and release of follicle stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary gland.

These hormones regulate the gonads (testes in males and ovaries in females), and therefore they are called gonado-tropins.

In both males and females, FSH stimulates production of the reproductive cells (sperm, eggs) and LH stimulates production of sex hormones (Testosterone, Estrogen and Progesterone) by the gonads.

An increase in sex hormone levels from the gonads inhibits GnRH production through a so-called negative feedback loop (increasing production slows down the stimulation) and Regulation of the reproductive system is a process that requires the action and reaction of hormones from the hypothalamus, the pituitary gland, and the gonads (ovaries and testicles), with constant communication between the hormone producing organs (glands) and their target cells so that the levels of all the important hormones do not go too high or too low (“balanced” hormone levels).

During puberty, in both males and females, the hypothalamus produces gonadotropin-releasing hormone (GnRH), which stimulates the production and release of follicle stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary gland.

These hormones regulate the gonads (testes in males and ovaries in females), and therefore they are called gonado-tropins.

In both males and females, FSH stimulates production of the reproductive cells (sperm, eggs) and LH stimulates production of sex hormones (Testosterone, Estrogen and Progesterone) by the gonads.

An increase in sex hormone levels from the gonads inhibits GnRH production through a so-called negative feedback loop (increasing production slows down the stimulation) and thereby reduce the release of the gonadotropins, so that the levels are always kept between certain critical levels to allow the system to work properly (system is in balance).

Hormonal imbalance:

As described before, the production of hormones is carefully regulated to keep the levels between certain critical boundaries. This is necessary so that the whole reproductive system works adequately.

An imbalance in the levels of certain critical hormones will therefore disturb the normal sequence of events in the menstrual cycle, which then results in either delayed development of eggs on the ovaries, or no development at all (female), or reduced sperm production (male).

Hormonal imbalances are the leading cause of infertility in women.

Because the hormones from the reproductive system regulate the menstrual cycle, imbalance in the hormone levels and production therefore results in  

disturbance of the normal menstrual cycle, resulting in an abnormal menstrual pattern or even total absence of menstruation.

For the purpose of this short discussion of hormonal imbalance and infertility, we will just limit the discussion to the most common infertility conditions in which hormonal imbalances play a role.

We will therefore not elaborate on imbalances of for example the thyroid hormone, either too high or too low, both of which can disturb the normal function of many organs, including the reproductive organs.

The most common conditions in which reproductive hormonal imbalances play a role are:

• Polycystic ovarian syndrome (PCOS) – add link
• Hyper-prolactinaemia
• Anovulation due to other causes

 Any of these three conditions have a common symptom, where the menstruation either occurs infrequently or is totally absent, and all of these are caused by infrequent or absent ovarian ovulation.

PCOS:

The most common hormonal imbalance associated with disturbed menstruation is Polycystic Ovarian Syndrome. We have been writing about this condition in previous papers published on the HART website.

Polycystic ovary syndrome is a disorder involving combinations of infrequent or absent menstrual periods, excess of male hormone (androgen) levels in the blood, and often (but not always) one or two ovaries showing multiple small follicles on ultrasound.

The ovaries develop numerous small collections of fluid, called follicles, and fail to release eggs (anovulation).  The anovulation results in absence of menstruation.

The diagnosis is usually made with:

• Medical history of infrequent or absent menstruation, and some of the other symptoms like acne, oily skin, abnormal hair growth.
• Physical examination concentrating on body weight (BMI), distribution of abnormal hair growth, and acne, with otherwise normal female pelvic examination.
• Blood tests showing abnormal levels of androgens, abnormal levels of FSH and LH, and (not absolutely required for the diagnosis) high or very high levels of anti-mullerian hormone (AMH).
• The excessive number of immature small follicles located in each ovary can be seen during a transvaginal ultrasound examination.

At least 50% of women with PCOS are obese class I (BMI > 30) or obese class II (BMI > 35).

The exact cause of polycystic ovary syndrome is unknown.

Early diagnosis and treatment along with (sometimes radical) weight loss may reduce the risk of long-term complications, such as type 2 diabetes, heart disease or cancer of the uterus, to name a few.

Additional factors in PCOS:

Excess insulin:

Insulin is the hormone produced in the pancreas that allows cells to use sugar (glucose).

In the case of insulin resistance, the ability to use insulin effectively is impaired, and the pancreas has to secrete more insulin to make glucose available to cells.

Excess insulin might also affect the ovaries by increasing androgen production, which may interfere with the ovaries’ ability to ovulate.

The best way to deal with Insulin resistance is weight reduction, often combined with medication.

 Treatments and drugs:

Polycystic ovary syndrome treatment generally focuses on management of each individuals’ main concerns, such as infertility, hirsutism, acne or obesity.

In young girls with PCOS usually the only request is to re-establish menstruation, which can easily be done with the combined oral contraceptive pill.

This of course is not the treatment of choice for a woman with PCOS who wants to fall pregnant. In those women ovulation needs to be restored. This can be done with the following treatment options.

 Lifestyle changes:

As a first step, in obese or very obese women, weight loss through a low-calorie diet combined with moderate exercise activities can restore ovulation which will result in a normal menstrual cycle. Even a modest reduction of 5-10 percent of body weight might already improve the condition dramatically.

Insulin resistance:

If insulin resistance has been established (high fasting insulin levels with normal glucose), metformin (Glucophage) can be prescribed. This is an oral medication for type 2 diabetes that improves insulin resistance and lowers insulin levels. This drug may help with ovulation and lead to regular menstrual cycles. It also slows the progression to type 2 diabetes and aids in weight loss if combined with a diet and an exercise program.

Ovulation induction:

For women who have PCOS and are trying to get pregnant, medication can be used to try and get the ovaries to start ovulating again.

Clomiphene citrate (Clomid, Fertomid, Serophene) is an oral anti-oestrogen medication that you take in the first part of your menstrual cycle. The effect of this medication needs to be followed up with your fertility doctor to make sure that the prescribed dose has indeed the desired effect. If the dose is too low, and no ovulation takes place, the dose may have to be increased.

Another oral medication for ovulation induction is letrozole (Femara) may help with ovulation when clomiphene fails. Again, this medication does not work for everyone, and not for everyone at the same dose, so it cannot be prescribed without supervision of the effect of the medication. It may require several visits per month to your fertility doctor to make sure that you are indeed ovulating.

If no ovulation is achieved using clomiphene or letrozole, other drugs such as gonadotropins — follicle-stimulating hormone (FSH) and luteinizing hormone (LH) medications that are administered by injection. This requires very careful supervision, because the women with PCOS may suddenly become very sensitive to this type of medication, and overreact.

If none of the medications has resulted in development of an egg on the ovary and ovulation, sometimes laparoscopic ovarian drilling may help, where during laparoscopy the thickened ovarian capsule is perforated with a few fine holes. This is usually not done as first line treatment, but as a last resort.

Hyper-prolactinaemia:

Prolactin is a hormone normally secreted by the pituitary gland after childbirth to stimulate milk production in the breast.

High levels of prolactin can interfere with normal regular ovulation in the female, resulting in absence of menstruation.

With normalization of levels of prolactin a normal menstrual cycle is usually restored.

 Abnormal levels of prolactin can be caused by medication used for depression (antidepressants) or psychiatric conditions (anti-psychotics), certain medication for high blood pressure, or medication used for reducing stomach acid. Very high levels can be caused by tumours in the pituitary gland (prolactinoma).

For mildly elevated levels, medication can be used to reduce the levels, for very high levels of prolactin, MRI or CT scan may be necessary to exclude a tumour.

Premature ovarian insufficiency (POI):

POI is a rare condition where the ovulation stops functioning at a young age (early or mid-thirties) due to the exhausted (or damaged) ovarian pool of eggs.

Whether primary ovarian insufficiency is related to problems inside the follicles, or to an earlier than normal drop in the number of follicles is unknown.

Causes of POI may also be related to genetic disorders, autoimmune disease, radiation or chemotherapy, and toxins such as cigarette smoke and pesticides, all of which will damage the pool of follicles in the ovaries.

POI is usually diagnosed by reviewing the woman’s medical history, pelvic exam, blood tests and ultrasound.

There is no proven treatment to restore normal ovarian function for women with POI. Recent developments have been looking at stem cell therapy to try and restore ovarian function. This is all still very experimental.

Treatments for women with POI can therefore only address the symptoms of premature menopause. These include hormone replacement therapy for hot   flushes, vaginal dryness, also with calcium supplements to protect the bones against osteoporosis, and maintaining a healthy weight and regular exercise.

If a woman with POI wishes to become pregnant, in vitro fertilization (IVF) using donor eggs is at the moment her only option.

Anovulation due to other causes:

A very rare cause of anovulation is hypothalamic dysfunction. 

Hypothalamic dysfunction can be due to surgery, tumors, radiation, brain injury and genetic conditions.

But it can also be caused by recent and severe weight loss or gain, excess physical and emotional stress, nutritional deficiencies, and a high or very low body weight. This can be seen in athletes who went through an extreme training program, or in young adults with excessive weight loss (anorexia).

As stated before, this discussion of hormonal imbalances related to infertility is not complete, but has addressed the more common disorders related to the reproductive system and the reproductive hormones.

 Male infertility and hormones:

Contrary to the situation in the female reproductive system, male hormone production is independent of gamete (reproductive cell) production.

Separate signals from the pituitary are sent for these two functions inside the testicles: FSH stimulates sperm production, LH stimulates testosterone production.

The failure of the pituitary to secrete follicle stimulating hormone (FSH) and luteinizing hormone (LH) results in disruption of testicular function and infertility. However, in men presenting with infertility, gonadotropin deficiency is extremely rare and only accounts for less than 0.5% of the causative factors of male infertility.

Other causes of male hormonal infertility:

A well-known cause is long term abuse of androgens or androgen-like hormonal treatment, often used in bodybuilding programs; this can completely suppress sperm production for a very long time, with often very slow recovery after the drugs have been stopped.

 Medication that have negative effect on sperm production via hormonal changes:

• Finasteride, frequently prescribed in the management of male pattern hair loss, is a strong anti-androgen and is found in Propecia. This hormone antagonist can interfere with sperm production.
• Certain anti-hypertensive medications (verapamil, alpha methyldopa) can cause raised prolactin, which can interfere with sperm production.
• Phenytoin (anti-epileptic) probably via hypothalamus

Get in touch with us should you have any questions or concerns regarding your fertility.