Sterility in females with hypo- or normogonadotropic ovarian insufficiency: Stimulation of follicle growth.
Sterility in males with hypo- or normogonadotropic hypogonadism: in combination with HCG to stimulate spermatogenesis.
Dosage & Administration
Sterility in females: The dosage of HMG for the induction of follicle growth in normo-or hypogonadotropic women varies according to the individual. The amount depends on ovarian reaction and should be checked by ultrasound examinations of the ovarian and measuring estradiol levels. If the HMG dosage is too high for the treated individual, multiple uni-and bilateral follicle growth can occur. HMG is administered intramuscularly or subcutaneously and in general, the therapy is begun with a daily dosage corresponding to 75-150 IU FSH. If the ovaries do not respond, the dosage can slowly be increased until a rise in estradiol secretion and follicle growth is evident. Treatment with the same dosage of HMG continues until the pre-ovulatory estradiol serum level is attained. If the level rises too quickly, the dosage should be reduced. To induce ovulation, 5000 or 10000 IU HCG are injected i.m. 1 to 2 days after the last HMG administration.
Note: After a HMG dosage too high for the corresponding individual has been administered the following HCG administration can cause an unintentional hyperstimulation of the ovaries.
Sterility in males: Initially, 2 X 5000 IU HCG a week are administered until a normal testosterone serum level is reached. Then, an additional dose of HMG (3 X 75-150 IU FSH + 75 - 150 IU LH) per week is administered for a few months.
Method of Administration
HMG is administered by intramuscular or subcutaneous injection.
Selection of patients
Women: 1. before treatment with HMG is instituted, a thorough gynecologic and endocrinologic evaluation must be performed. This should include a hysterosalpingogram (to rule out uterine and tubal pathology) and documentation of anovulation by means of basal body temperature, serial vaginal smears, examination of cervical mucus, and determination of serum (or urine) progesterone, urinary pregnanediol and endometrial biopsy. 2. Primary ovarian failure should be excluded by the determination of gonadotropin levels. 3. Careful examination should be made to rule out the presence of an early pregnancy. 4. Patients in late reproductive life have a greater predilection to endometrial carcinoma as well as a higher incidence of anovulatory disorders. Cervical dilation and curettage should always be done for abnormal uterine bleeding or other signs of endometrial abnormalities.
Men: Patient selection should be made based on a documented lack of pituitary function. Prior to hormonal therapy, these patients will have low testosterone levels and low or absent gonadotropin levels. Patients with primary hypogonadotropic hypogonadism will have a subnormal development of masculinization, and those with secondary hypogonadotropic hypogonadism will have decreased masculinization.
Toxic effects caused by HMG are unknown in humans. There is no evidence of teratogenic, mutagenic and carcinogenic activity of HMG. Antibodies against HMG can be built up in single cases following repeated cyclical administration of HMG, causing the treatment to be ineffectual.
Special warnings and special precautions for use
In pregnancies occurring after induction of ovulation with gonadotropic preparations, there is an increased risk of miscarriage, multiples and ectopic pregnancies. HCG should not be administered to induce ovulation in females whose ovaries have unintentionally been hyper-stimulated. When treating sterile women, ovarian activity should be checked (ultrasound and estradiol levels in serum respectively) prior to HMG administration. During treatment, these tests should be carried out every one to two days until stimulation occurs. Ovarian reaction can also be measured using a cervix index. Close supervision is imperative during treatment. Treatment should be immediately discontinued if unintentional hyper-stimulation occurs. This warning is particularly important with respect to patients with polycystic ovarian disease. The severe form of ovarian hyper-stimulation syndrome may be life-threatening and is characterized by large ovarian cysts (prone to rupture), ascites, very often hydrothorax and occasionally thromboembolic phenomena.
PREGNANCY AND LACTATION
There is no indication for HMG to be used during pregnancy and lactation period
Effects on ability to drive and use machines