Gonadotropin preparations: past, present, and future perspectives

Birmingham,; Alabama,

doi:10.1016/j.fertnstert.2008.08.031

Cited by 60 publications

(52 citation statements)

References 33 publications

(25 reference statements)

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“…The two hormones differ in the composition of their carbohydrate moieties, which affect bioactivity and half-life. The half-life of LH is 20 minutes, whereas the half-life of hCG is 24 hours (26). …”

Section: Expert Commentarymentioning

confidence: 99%

Hypogonadotropic Hypogonadism Revisited

Fraietta¹,

Zylberstejn²,

Esteves³

2013

Clinics

192

134

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Impaired testicular function, i.e., hypogonadism, can result from a primary testicular disorder (hypergonadotropic) or occur secondary to hypothalamic-pituitary dysfunction (hypogonadotropic).Hypogonadotropic hypogonadism can be congenital or acquired. Congenital hypogonadotropic hypogonadism is divided into anosmic hypogonadotropic hypogonadism (Kallmann syndrome) and congenital normosmic isolated hypogonadotropic hypogonadism (idiopathic hypogonadotropic hypogonadism). The incidence of congenital hypogonadotropic hypogonadism is approximately 1-10:100,000 live births, and approximately 2/3 and 1/3 of cases are caused by Kallmann syndrome (KS) and idiopathic hypogonadotropic hypogonadism, respectively.Acquired hypogonadotropic hypogonadism can be caused by drugs, infiltrative or infectious pituitary lesions, hyperprolactinemia, encephalic trauma, pituitary/brain radiation, exhausting exercise, abusive alcohol or illicit drug intake, and systemic diseases such as hemochromatosis, sarcoidosis and histiocytosis X.The clinical characteristics of hypogonadotropic hypogonadism are androgen deficiency and a lack/delay/stop of pubertal sexual maturation. Low blood testosterone levels and low pituitary hormone levels confirm the hypogonadotropic hypogonadism diagnosis. A prolonged stimulated intravenous GnRH test can be useful. In Kallmann syndrome, cerebral MRI can show an anomalous morphology or even absence of the olfactory bulb.Therapy for hypogonadotropic hypogonadism depends on the patient's desire for future fertility. Hormone replacement with testosterone is the classic treatment for hypogonadism. Androgen replacement is indicated for men who already have children or have no desire to induce pregnancy, and testosterone therapy is used to reverse the symptoms and signs of hypogonadism. Conversely, GnRH or gonadotropin therapies are the best options for men wishing to have children. Hypogonadotropic hypogonadism is one of the rare conditions in which specific medical treatment can reverse infertility.When an unassisted pregnancy is not achieved, assisted reproductive techniques ranging from intrauterine insemination to in vitro fertilization to the acquisition of viable sperm from the ejaculate or directly from the testes through testicular sperm extraction or testicular microdissection can also be used, depending on the woman's potential for pregnancy and the quality and quantity of the sperm.

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Section: Expert Commentarymentioning

confidence: 99%

Hypogonadotropic Hypogonadism Revisited

Fraietta¹,

Zylberstejn²,

Esteves³

2013

Clinics

192

134

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show abstract

“…The urine contaminants, present in the older preparations of urinary hMG and FSH, prevented the use of the subcutaneous route due to potential local reactions [14, 15], though several clinical studies indicated that the risk of allergic reactions was minimal [16, 17]. More recently, the new highly purified FSH (hp-FSH) and highly purified hMG (hp-hMG) preparations have reached a higher purification grade equivalent to that of FSH obtained by recombinant DNA technology (rFSH) [18]. Their purification grade allows a safe and well-tolerated subcutaneous administration.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics and Pharmacodynamics of Follicle-Stimulating Hormone in Healthy Women Receiving Single and Multiple Doses of Highly Purified Human Menotrophin and Urofollitrophin

et al. 2016

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Background and ObjectiveHighly purified human menotrophin and urofollitrophin preparations obtained from human urine via a novel patented purification method have been tested over a timeframe of 14 years in the studies presented in this article. The objective of the studies was to investigate the pharmacokinetics and the pharmacodynamics of follicle-stimulating hormone (FSH) after single subcutaneous and intramuscular doses and multiple subcutaneous doses of the tested preparations in healthy fertile pituitary-suppressed women.DesignsWe performed five open, randomised, crossover, single-dose bioequivalence and/or bioavailability studies and one open, multiple-dose, pharmacokinetics and pharmacodynamics study.Study Subjects and TreatmentsThe six studies included 121 healthy fertile women taking their usual combined oral contraceptives for 3 months before the study: Study 1: 300 international units (IU) of highly purified menotrophin as single subcutaneous and intramuscular doses. Study 2: 300 IU of highly purified menotrophin (test formulation vs. comparator) as single subcutaneous doses. Study 3: 300 IU of highly purified urofollitrophin (hp-FSH) (test formulation vs. comparator) as single subcutaneous doses. Study 4: 300 IU (2 × 150 IU vs. 4 × 75 IU) of hp-FSH as single subcutaneous doses. Study 5: 225 and 445 IU of hp-FSH as single subcutaneous doses. Study 6: daily 225 IU of hp-FSH as subcutaneous doses for 5 consecutive days.Main Outcome MeasuresThe main outcome measures were the FSH pharmacokinetic parameters, estradiol concentrations, and the number and size of the follicles.ResultsFSH after single subcutaneous and intramuscular injections of menotrophin or urofollitrophin attained a systemic peak (maximum) concentration (C max) that was on average consistent throughout the first four studies and ranged from 4.98 to 7.50 IU/L. The area under the plasma concentration–time curve (AUC) from administration to the last observed concentration time t (AUCt) ranged from 409.71 to 486.16 IU/L·h and the elimination half-life (t ½) ranged from 39.02 to 53.63 h. After multiple doses of urofollitrophin (225 IU) for 5 days, FSH attained a mean C max of 14.93 ± 2.92 IU/L and had an AUC during the time interval τ between two consecutive doses at steady state (AUCτ) of 322.59 ± 57.92 IU/L·h, which was similar to the mean AUCt after a single subcutaneous dose of 225 IU of urofollitrophin in study 5 (306.82 ± 68.37 IU/L·h).ConclusionsIn our studies, the intramuscular and subcutaneous routes of menotrophin were equivalent; both menotrophin and urofollitrophin were bioequivalent to their marketed reference; FSH kinetic parameters following injection of urofollitrophin were dose proportional and independent from the administered concentration; and multiple doses of FSH increased estradiol levels and enhanced growth of follicles with a good dose–response correlation. Local tolerability was excellent throughout the six studies.

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“…hCG is an LH analog purified from the urine of pregnant women or through recombinant technology (34). Discovered in 1932, hCG has been used in women to stimulate follicular maturation.…”

Section: Therapeutic Approachesmentioning

confidence: 99%

Testosterone replacement in the infertile man

Majzoub

Sabanegh

2016

Transl. Androl. Urol.

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Hypogonadism is a common clinical condition affecting men of different age groups. In addition to its sexual consequences, it has several implications posing significant concerns for a man’s health and well-being. Recent advances in testosterone (T) supplementation have facilitated hypogonadism treatment. Despite that, patients complaining of infertility or seeking conception are still hindered by the unfavorable effects supplemental T has on testicular function. Consequently, alternative approaches that can stimulate endogenous T production are favored. Selective estrogen receptor modulators, gonadotropins and aromatase inhibitors (AIs) can be successful in restoring serum T levels, preserving fertility, and providing symptomatic relief.

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Gonadotropin preparations: past, present, and future perspectives

Cited by 60 publications

References 33 publications

Hypogonadotropic Hypogonadism Revisited

Hypogonadotropic Hypogonadism Revisited

Pharmacokinetics and Pharmacodynamics of Follicle-Stimulating Hormone in Healthy Women Receiving Single and Multiple Doses of Highly Purified Human Menotrophin and Urofollitrophin

Testosterone replacement in the infertile man

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