In the Kinderwunsch Institut Dr Loimer in Linz, a professional medication-based hormone treatment is recommended for those who have the unfulfilled desire to have children.
The hypothalamus is an area in the diencephalon that functions as a control centre in the body. The hypothalamus coordinates body temperature as well as eating, sleeping and sexual behaviour. It also plays an important role in regulating the female cycle and in the formation of various hormones. If there is a disorder of the hypothalamus (e.g. eating disorders or excessive exercise), it can happen that it does not send signals (liberins and statins) to the pituitary gland responsible for the production of hormones LH and FSH in a steady rhythm. As a result, ovulation does not occur and there is no period. So-called hypothalamic amenorrhea (lack of menstrual bleeding) can occur. To ensure that GnRH is produced again and released steadily in the hypothalamus – and the body has a chance of a successful pregnancy – there are different methods of therapy. One possibility is, for example, the administration of GnRH by a pump (LUTRELEF ® 3.3mg gonadorelin acetate) which is worn directly on the body. This pump delivers the drug into the subcutaneous tissue. The catheter is changed every 3 days. The therapy has a very high ovulation rate of almost 100 per cent and therefore a high rate of pregnancy at around 40 per cent per cycle. After three to four cycles, approximately 84 per cent of patients are pregnant. Another treatment method is ovarian stimulation with gonadotropins LH and FSH.
The pituitary gland is the central control organ for many of the hormonal functions in the body; it is where the most important hormones are formed and released.
When the pituitary gland does not produce enough hormones, this is called pituitary insufficiency. It can occur as a result of a tumour or other diseases of the pituitary gland. Pituitary insufficiency does not always affect all of the different hormonal systems at the same time. It is also possible that only one or two hormonal systems fail (for example, failure of sex hormones or diabetes insipidus). If a hormone deficiency occurs due to a pituitary insufficiency, this usually has to be treated with medication. The natural function of the pituitary can be imitated.
Benign tumours can occur in the pituitary gland, malignant ones are rare. Some pituitary gland tumours are hormone-active and thus produce more hormones than the human body needs. In contrast, there are also hormone-inactive pituitary tumours.
Treatment of AGS and late onset AGS
Adrenogenital Syndrome (AGS) is a group of congenital metabolic diseases in which the production of hormones in the adrenal cortex is disturbed. In the adrenogenital syndrome, congenital genetic mutations (CYP21A2 is located on chromosome 6) of individual enzymes that play an important role in the formation of hormones lead to an increased production of male hormones with a reduced formation of cortisol and aldosterone. In women with AGS, risk minimisation consists of a good medication plan with glucocorticoids and, if necessary, mineralocorticoids in sufficient doses. A therapeutic attempt with low-dose glucocorticoid (e.g. prednisolone 5mg in the evening) is being discussed, but so far only a few studies are available).
Ovaries (estrogen and progesterone)
The most important estrogens occurring in the body are estrone, estriol and above all estradiol, which is also known as the female fertility hormone. They play an important role, especially in the first half of the female cycle. Because they prepare ovulation – and with it the uterus for the possible implantation of the egg cell. In addition, they have a direct impact on various organs and tissues. For example, they protect women from a heart attack during their fertile years, ensure smooth skin by stimulating the formation of collagen, and strengthen bones by stimulating cells that build bone mass. In addition, estrogens have a beneficial effect on the production of serotonin and other messenger substances in the brain and is therefore mood-enhancing and anti-depressant. In some women, however, the influence of estrogen leads to increased water retention in the tissue, this manifests itself, for example, through cyclical feelings of tension in the chest.
Progesterone is often referred to as ‘the body’s own progestin’ and is the dominant hormone during the second half of the female cycle. The fact that the basal temperature is constantly increasing during this time is mainly due to progesterone. Progesterone is produced in the ovaries in the corpus luteum, which is what is left over after ovulation. If fertilisation does not occur, the corpus luteum dies within about 14 days and progesterone production decreases. One of the most important tasks of progesterone is to prepare the uterine lining that has built up in the first half of the cycle so that a fertilised egg can implant and grow. Like estrogen, progesterone is also of great importance for bone health and increases formation of collagen, which helps stop the formation of wrinkles in the skin. It also has an anti-depressant effect, influences the immune system, regulates androgens, has a stimulating effect on the libido and supports the action of thyroid hormones. In addition, progesterone promotes water excretion and has a dehydrating effect.
Treatment of PCOS (hyperandrogenemia)
The impairment of fertility in PCOS is based on a problem with ovulation where there is infrequent or no ovulation. Treatment is based on a staged system. Adjusting the metabolism through lifestyle changes with a change in diet and physical activity, and thereby weight regulation, leads to improvement in excess male hormones in women with PCOS.
Hormonal stimulation with clomiphene continues to be the established standard therapy. According to the latest guidelines of ESHRE, letrozole is the first-line treatment for PSOS. Gonadotropins are the second choice for ovulation induction. Drug therapy to induce ovulation carries the risk of strong reactions and up to ovarian hyperstimulation syndrome and the occurrence of a multiple pregnancy. The controlled ovulation induction with ultrasound examination and, if necessary, termination of the stimulation counteract these risks.
The results of the use of metformin in women with and without proven insulin resistance are now available from many studies. Metformin can also be used to induce ovulation with medicinal stimulation. The main limiting factors for its use are the side effects in the gastrointestinal tract. There is currently insufficient data on the use of inositol for the purpose of increasing fertility in women with polycystic ovary syndrome. An alternative to drug therapy is laparoscopic ovarian drilling.
In the 4 to 8 weeks prior to conception, an optimal diabetes reading should be available (check, for example, HbA1c). It should be noted that progestins can temporarily worsen glucose tolerance, so in the case of planned luteal phase support, HbA1c determination with progestin administration in advance makes sense. Diabetics should be informed about the potentially increased risk of miscarriage. In the case of type I DM, the possible genetic background/causes should be clarified.
Women also produce small amounts of male hormones (androgens) including testosterone and DHEA-S. They are produced in the ovaries, adrenal cortex and adipose tissue. The female body needs them for the production of estrogens, the most important group of female hormones. However, too much testosterone and DHEA-S can severely impair ovarian function and also lead to some male physical characteristics (increased hair growth on certain parts of the body, acne and hair loss). If more cysts form in the ovaries and the cycle is disturbed, we speak of PCOS. An overproduction of male sex hormones often occurs together with being very overweight. Most affected women are advised to normalise their hormonal balance in a natural way by losing weight. In other cases, medication can help reduce both the production of male hormones and their effect on the female cycle.
Treatment with male hormones with diminished ovarian reserve
For several years now, we have been using the male hormone dehydroepiandrosterone (DHEA) with great success to treat women with reduced egg cell reserves due to advanced age or premature ovarian aging. We were able to demonstrate the remarkably positive effect of treatment with DHEA, in which the ovarian function of these women is regenerated. So far, we have found that DHEA not only increases the number and quality of egg cells available for fertilisation, but it also shortens the time required for fertility treatment and increases the chances of spontaneous conception. In addition, DHEA reduces the risk of miscarriage – an important factor particularly for older women who want to have children.
Luteal phase defect
A luteal phase defect is a dysfunction of the corpus luteum in the second half of the cycle, which is often caused by a disturbance in ovarian function. It is one of the most common reasons for infertility. Once the diagnosis has been made, in most cases it is not the end of hope for a baby. Women with a progesterone deficiency can also get pregnant with the help of hormone therapy. Luteal phase defect can be treated well with medications that compensate for the impaired hormone production. Preparations such as Utrogestan, Arefam or Duphaston, Proluton Depot clearly support weakness in the luteal phase.
Elevated prolactin (hyperprolactinemia)
Elevated prolactin should be treated in connection with the desire to have children. Various prolactin reducers can be used as a treatment, the best-known and those that have been most studied are bromocriptine and cabergoline. Current studies show a slight advantage in the effectiveness of cabergoline. The discussion about possible damage to the heart valves through long-term dopaminergic therapy, including in hyperprolactinemia, has not yet been concluded.
The intake of cortisone when trying to get pregnant serves, among other things, to adapt to stress, regardless of whether it has an internal or external cause. The regulation of hormone production takes place in a separate control loop between the hypothalamus, pituitary gland and the ovaries, with higher brain regions also influencing hormone production. Disturbances in the production of cortisone thus also effect the fertility of the women. The intake of cortisone can therefore help women with hormonal problems to get pregnant.
Hypothyroidism (underactive thyroid)
Fertility patients with moderate to severe iodine deficiency (measured by iodine excretion) have reduced fertility compared to patients with a normal iodine supply. Therefore, women who want to have children are recommended to take additional iodide. The WHO recommends the daily administration of 250 µg iodide during pregnancy and breastfeeding. Women of childbearing age should consume an average of 150 µg/day of iodide.
Hyperthyroidism (overactive thyroid):
Thyroid antibodies are peculiar and can also trigger hyperthyroidism in babies. In the case of a mother’s hyperthyroidism that needs treatment during pregnancy, the therapeutic options (anti-thyroid drugs, radio-iodine therapy, surgery) are all associated with endangering or impairing the baby. Therefore, therapy for hyperthyroidism should be given before IVF. Women with SD antibodies have slightly higher risk of miscarriage than women without. So far there is no evidence that thyroxine therapy changes this. For women with SD antibodies and a TSH value of <2.5mU/L, on the other hand, a meta-analysis showed that the probability of a live birth is increased if thyroxine was taken.