Pharmacotherapy of Kallmann syndrome is a hormonal therapy, which is used as an adjuvant treatment of Kallmann syndrome.Treatment for KS can be divided into hormone replacement therapy and fertility treatments. The treatment regimen for CHH (congenital hypogonadotropic hypogonadism- a group of conditions, including Kallmann syndrome, which is characterized by hypogonadism due to an impaired secretion of gonadotropins, including follicle-stimulating hormone and luteinizing hormone) is principally determined by whether the goal is to develop secondary sexual characteristics (features that appear during puberty in humans) or to induce fertility as well.
Hormone replacement therapy (HRT)
The aim for hormone replacement therapy (HRT) for both men and women is to ensure that the level of circulating hormones (testosterone for men and oestrogen/progesterone for women) is at the normal physiological level for the age of the patient. At first the treatment will produce most of the physical and psychological changes seen at puberty, with the major exception that there will be no testicular development in men and no ovulation in women.
After the optimum physical development has been reached HRT for men will continue to ensure that the normal androgen function is maintained; such as libido, muscle development, energy levels, hair growth, and sexual function. In women, a variety of types of HRT will either give a menstruation cycle or not as preferred by the patient. HRT is very important in both men and women to maintain bone density and to reduce the risk of early onset osteoporosis (disease where increased bone weakness leads to bone fragility and therefore they are more likely to break).
The fertility treatments used for both men and women would still include hormone replacement in their action.
There is a range of different preparations available for HRT for both men and women; a lot of these, especially those for women are the same used for standard HRT protocols used when hormone levels fall in later life or after the menopause.
For the men testosterone replacement is achieved either by using daily capsules, daily gel or patches, fortnightly injections, three monthly injections, or six monthly implants. Tablet/capsule forms of HRT rarely give sufficient testosterone levels suitable for men with KS. Different formulations of testosterone are available for treatment which will contain single or multiple forms of testosterone.
The three monthly injection of testosterone undecanoate has become very popular over the past ten years. After the first two injections which are six weeks apart, injections are taken every three months and give good testosterone levels throughout the three-month period with no noticeable tailing-off of levels at the end of the injection cycle. Some patients only require the injection every six months. These injection intervals might be adjusted depending on the response of the individual. Some treatments may work better with some patients than others so it might be a case of personal choice as which one to use.
There are no specialist HRT treatments available just for women with KS but there are multitude of different HRT products on the market including oral contraceptives and standard post-menopause products. Pills are popular but patches are also available. It may take some trial and error to find the appropriate HRT for the patient depending on how her body reacts to the particular HRT. Specialist medical advice will be required to ensure the correct levels of oestrogen and progesterone are maintained each month, depending on whether the patient requires continuous HRT (no-bleed) or a withdrawal option to create a "menstrual" type bleed. This withdrawal bleed can be monthly or over longer time periods depending on the type of medication used.
Fertility treatments
Fertility treatments for people with KS will require specialist advice from doctors experienced in reproductive endocrinology. There is a good success rate for achieving fertility for patients with KS, with some experts quoting up to a 70% success rate, if IVF (in vitro fertilisation- an eg gis fertilised with sperm outsider of the body) techniques are used as well. However, there are factors that can have a negative effect on fertility and specialist advice will be required to determine if these treatments are likely to be successful.
Fertility treatments involve the administration of the gonadotropins LH and FSH in order to stimulate the production and release of eggs and sperm. Women with KS have an advantage over the men as their ovaries normally contain a normal number of eggs and it sometimes only takes a few months of treatment to achieve fertility while it can take males up to two years of treatment to achieve fertility.
Human chorionic gonadotrophin (hCG- a hormone produced by the placenta after implantation) is sometimes used to stimulate testosterone production in men and ovulation induction in women. For men it acts in the same way as LH (luteinizing hormone is responsible in women for ovulation and in men for production of testosterone by Leydig cells) – also been mentioned in previous paragraph; stimulating the Leydig cells in the testes to produce testosterone. Some men with KS take hCG solely for testosterone production.
Human menopausal gonadotrophin (hMG) is used to stimulate sperm production in men and for multiple egg production and ovulation induction in women. It contains a mixture of both LH and FSH (a hormone regulating development, growth, pubertal maturation, and reproductive processes of the body). In men the FSH acts on the sperm producing Sertoli cells in the testes. This can lead to testicular enlargement but can take anything from 6 months to 2 years for an adequate level of sperm production to be achieved.
Purified forms of FSH are also available and are sometimes used with hCG instead of using hMG.
Females with KS would normally require both hCG and FSH in order to achieve fertility. Other cases of female infertility can be treated with just FSH but females (and most males) with KS would require the use of both forms of gonadotropin injection.
Injections can be intramuscular but are normally taken just underneath the skin (subcutaneous) and are normally taken two or three times a week.
For both men and women, an alternative method (but not widely available), is the use of an infusion pump to provide GnRH (or LHRH) in pulsatile doses throughout the day. This stimulates the pituitary gland to release natural LH and FSH in order to activate testes or ovaries. The use of Kisspeptin (a protein that regulates the release of GnRH from the hypothalamus) delivered in the same pulsatile manner is also under evaluation as a possible treatment for fertility induction.
The major challenges associated with the treatment and management of KS include the appropriate timing of the treatment and how to promote adherence to treatment, especially during the transitioning of young adults from pediatric to adult care because any gaps can have considerable consequences (lack of reproductive features, poorly defined secondary sexual characteristics, infertility, osteoporosis, etc.).
While properly followed treatment no complication have been described.
KS can be managed more effectively if it is recognized during the early stages. The initial assessment of this disease typically relies on the physical examination and data obtained in primary clinics. Because these patients are often admitted by a variety of different clinics (endocrinology, pediatrics, neurosurgery, urology, obstetrics, and gynecology), a correct initial diagnosis and subsequent referrals are critical for appropriate follow-up visits and the systematic management of the disease on a long-term basis. Timely treatment to induce puberty can be also crucial for sexual, bone, and metabolic health and for the minimization of the psychological effects that can be associated with KS. The treatment regimen for CHH is principally determined by whether the goal is to develop secondary sexual characteristics (virilization or estrogenization) or to induce fertility as well. In most cases, fertility can be induced under specific regimens of testosterone treatment in males and estrogen/progesterone treatment in females. Patients typically require lifelong treatment to maintain normal sexual function.
