MOST PATIENT HAVE GONADOTROPIN-RELEASING HORMONE DEFICIENCY & HAVE NO ANOSMIA OR HYPOSMIA IN CONTRAST TO KALLMANN SYNDROME.
Medical Care
" Evaluation and therapy can usually be implemented on an outpatient basis. Inpatient evaluation and treatment may be necessary for patients with congenital heart disease or acute adrenocortical insufficiency.
" All postpubertal-age patients with Kallmann syndrome (KS) and idiopathic hypogonadotropic hypogonadism (IHH) are candidates for gonadal steroid replacement therapy in the absence of specific contraindications. Additional therapies to restore fertility can be implemented on request.
" Behavioral modification and psychological counseling may benefit individuals with hypothalamic amenorrhea. Such approaches should be offered before estrogen replacement therapy.
" Medical therapies are used to treat associated conditions, including osteoporosis, adrenocortical insufficiency, congenital heart disease, and neurologic disorders.
Surgical Care
" Assisted reproductive technologies, including in vitro fertilization (IVF), zygote intrafallopian transfer (ZIFT), and gamete intrafallopian transfer (GIFT), have been used successfully when male patients with KS or IHH do not achieve adequate sperm counts on either GnRH or gonadotropin therapy.
"
" Patients with KS and congenital heart disease may need corrective surgery. A detailed description of the pertinent procedures is beyond the scope of this review.
"
" Patients with cleft lip or palate also need surgical correction.
Diet
" No dietary restrictions are required in the absence of congenital heart disease. Salt restriction (adult Na+ intake <2 g/d) is advised for patients with congestive heart failure.
"
" All patients must ensure an adequate calcium (1200 mg/d) and vitamin D (600-800 U/d) intake, especially if they are osteopenic. Dietary supplements may be necessary for patients to achieve these goals.
Activity
" Routine activity restrictions are not necessary; however, patients with osteoporosis need to avoid high-impact sports and situations conducive to falls.
"
" Activity restrictions are also appropriate in patients with certain forms of congenital heart disease or seizures.
DRUG TREATMENT :
Patients with KS or IHH who do not desire fertility should have gonadal steroid replacement therapy, including testosterone in males and estrogen-progestin in females, unless contraindicated. Fertility options include either GnRH (gonadorelin) or gonadotropin-based regimens. Clomiphene may also be used in women with hypothalamic amenorrhea.
1. Androgens :
Androgen replacement in males with KS or IHH restores libido, erectile function, and well-being. In addition, androgen replacement promotes the development of secondary sex characteristics (eg, facial, axillary, and pubic hair) and increases muscle strength. A short course of androgens in infancy leads to penile growth in infants with micropenis. Androgen replacement also improves bone density and may prevent osteoporosis. Either parenteral or transdermal testosterone is the drug of choice for androgen replacement. Orally administered alkylated androgens should be avoided because of the risk of serious hepatic toxicity, including peliosis hepatitis, cholestasis, and hepatocellular carcinoma.
- TESTOSTERONE
2. STEROID HORMONES :- ESTROGEN REPLACEMENT THERAPY IN FEMALES PROMOTES DEVELOPMENT OF SECONDARY SEX CHARACTERS, INCLUDING BREAST DEVELOPMENT & MENSTRAL CYCLE & IT MAY PREVENT OSTEOPOROSIS. ORAL CONTRACEPTIVES MAY BE USED AS REPLACEMENT THERAPY IN YOUNG WOMEN.
- CONJUGATED ESTROGENS ( PREMARIN )
- ETHYNYL ESTRADIOL
- ESTRADIOL
- TRANSDERMAL ESTRADIOL
3. PROGESTINS : Medroxyprogesterone is usually administered to female patients on estrogen replacement therapy for 12-14 d/mo. Induces secretory changes in endometrium and leads to withdrawal bleeding, which is essential for prevention of estrogen-induced endometrial hyperplasia. Patients on combination oral contraceptives already receive a progestin and do not need additional medroxyprogesterone therapy.
- MEDROXYPROGESTERONE
4. HYPOTHALAMIC RELEASING HORMONES : Pulsatile administration of gonadorelin (GnRH) by subcutaneous (SC) or preferably intravenous (IV) infusion restores pituitary-gonadal axis function and fertility in the majority of people with KS and IHH. Some patients with GnRH receptor mutations may respond to high-dose GnRH therapy.
- GONADORELIN
5. GONADOTROPINS : These successfully restore fertility in most patients with KS or IHH. Patients with IHH and AHC may have an intrinsic defect in spermatogenesis and may not respond to gonadotropin therapy. In men, hCG should be used alone for as long as 1 year and may be effective alone in patients with partial gonadotropin deficiency. Having verified that androgen levels are normal on hCG therapy, FSH should be added to the regimen after that period. In females, ovulation induction protocols are complex and vary. A detailed discussion of these protocols is beyond the scope of this review.
- FOLLICLE STIMULATING HORMONE
- HUMAN CHORIONIC GONADOTROPIN
6. OVULATION STIMULATORS : IT ACTS AS AN ANTIESTROGEN TO DECREASE NEGATIVE ESTROGEN FEEDBACK ON HYPOTHALAMUS. IN ADDITION CLOMIPHENE MAY HAVE EFFECTS ON THE PITUITARY GLAND AND OVARIES & CAN INDUCE OVULATION IN WOMEN WITH HYPOTHALAMIC AMENORRHOEA. CLOMIPHENE IS NOT LIKELY TO BE EFFECTIVE IN PATIENTS WITH KALLMANN SYNDROME & IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM.
- CLOMIPHENE