2151 Hypothalamic releasing hormones

Pharmacology and toxicology

The hypothalamic control of anterior pituitary function is performed by a group of hormones referred to as releasing hormones. Because of their molecular size, hypothalamic releasing hormones can cross the placenta. The following hormones belong to this group.

Thyrotropin releasing hormone (TRH)

Synthetic analogs are protirelir(=l) corticorelii^lJiH controls thyroid function via the thyroid-stimulating hormone (TSH), and also stimulates prolactin secretion. There is evidence that TRH exerts a significant relaxant effect in human myometrium and in human umbilical vasculature. These effects could have clinical implications in treated pregnant women (Potter 2004). Some authors have suggested that TRH added to prenatal glucocorticoids in women at risk of preterm delivery could reduce pulmonary problems and neonatal lung disease. Nevertheless, some studies and an extensive review of the literature published on this topic, with over 4600 women analyzed, concluded that prenatal TRH in addition to corticosteroids did not reduce the risk of neonatal respiratory diseases, but can produce adverse effects in both women and their infants (Crowther 2004, 1997, Ballard 1998). Some authors described an association between maternal treatment with TRH and delay in mental development in antenatal exposed children (Briet 2002). Thus, there seems to be a general consensus that in preterm infants at risk for lung disease, antenatal administration of TRH and glucocorticoids is no more beneficial than glucocorticoids alone.

Gonadotropin releasing hormone (GnRH) or luteinizing hormone releasing hormone (LHRH)

Releasing hormones are responsible for regulating the synthesis and secretion of FSH and LH. Many synthetic human GnRH agonists are marketed, including buserelin, gonadorelin, goserelin, leuprore-lirt, nafarelin, and triptorelin. Cetrorelix and ganirelix are inhibitors of GnRH. In women, GnRH agonists have been used to treat estrogen-dependent breast cancer, endometriosis, hirsutism, and polycystic ovarian syndrome, but the widespread use of protocols using GnRH agonists/ antagonists in assisted reproductive technologies has led to an increasing number of pregnant women being exposed to these types of drugs. Most of the data concerning the safety of the GnRH analogs have not demonstrated serious side effects, such as increase in the incidence of miscarriage, birth defects, or fetal growth restriction, in human pregnancies exposed to GnRH (Tarlatzis 2004,

Ludwig 2001, Elefant 1995, Wilshire 1993). Nevertheless, concern about its potential side effects on the CNS persists. In a controlled study, 6 pregnancies exposed to GnRH agonist and 20 unexposed controls were followed to a mean age of 8 years. Four of the ante-natally exposed children showed neurological developmental disorders, including attention deficit hyperactivity disorder (three children), motor difficulties (three children), speech disturbances (one child) and epilepsy (one child). The authors suggested a possible toxic effect of GnRH analogs on development (Lahat 1999). More recently, another case of one 7-year-old child with attention deficit hyperactivity disorder exposed to GnRH agonist during pregnancy has been reported (Papanikolau 2005).

The available information concerning children exposed to GnRH antagonist is still rare. In a study carried out on the perinatal outcome of pregnancy in a total of 73 infants born to patients treated with the GnRH antagonist (ganirelix) during ovarian stimulation for in vitro fertilization (IVF) or intra-cytoplasmatic sperm injection (1CSI), the Incidence of adverse obstetrical and neonatal outcome was comparable with reported incidences for IVF-embryo transfer pregnancies. Only one child was diagnosed with a major congenital malformation -a boy with Beckwith-Wicdemann syndrome (BWS). Five infants had minor anomalies (Olivennes 2001). Nevertheless, it is important to note that an association between imprinting disorder, such as BWS, and assisted reproductive technology (IVF and IC1) is suspected (Chang 2005, Shiota 2005, Maher 2003).

Growth hormone releasing hormone (GHRH)

Synthetic analogs arc sermorelii[=J somatoreli{=jesz hormones reduce blood flow to the uterus arid inhibit endometrial proliferation. For these reasons, they are used prcoperatively in treating uterine leiomyomata. In case of inadvertent use during pregnancy, miscarriage and fetal growth restriction are conceivable; however, these effects havr got been reported to date.

Somatoslatit{L=~Jibits the release of both growth hormone and TSH. In this respect, it is unique among the hypothalamic hormones. Therapeutically, it is used for carcinoids and to lower the growth hormone concentration in acromegaly_A synthetic octapeptide derivative of somatostatin, ocfreoi/i/<(^F^vailable for therapeutic use. In a few individual cases octrcotidlfwas used during a part of pregnancy or throughout pregnancy for treatment of acromegaly; no malformations or other adverse effects were reported (Cozzi 2006, Blackhurst 2002, Neal 2000, Takeuchi 1999, Colao 1997). It was reported that ultrasound monitoring of fetal parameters during octreotide long-acting repeatable treatment in a patient suggested the possibility of leLal growth retardation, prompting drug dosage decrease (Fassnacht 2001). However, experience with use of octreotide during pregnancy is insufficient for a well-grounded assessment of the teratogenic potential. There is no experience with exposure during pregnancy with lameotide, an analog of somatostatin or with pegpisomant, a somatotropin receptor antagonist.

Recommendation. There are only rare indications for using hypothalamic releasing hormones during pregnancy. Inadvertent use is not grounds for either termination of the pregnancy or invasive diagnostic procedures.

The ADHD Success Formula

The ADHD Success Formula

This is an audio and guide that will help you battle through ADHD and Accomplish Twice As Much In Half The Time. Learn more by download your very own copy today.

Get My Free Ebook


Post a comment