Menotropin

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Menotropin
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Menotropin (also called human menopausal gonadotropin or hMG) is a hormonally active medication for the treatment of fertility disturbances. Frequently the plural is used as the medication is a mixture of gonadotropins. Menotropins are extracted from the urine of postmenopausal women. [1]

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Description and usage

Urine of postmenopausal women reflects the hypergonadotropic state of menopause -levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH) are high - and contain a mixture of these gonadotropins. [2] [3] [4] Other protein substances may be present, including small amounts of human chorionic gonadotropin (hCG). [1] In 1949 Piero Donini found a relatively simple method to extract gonadotropins from urine of postmenopausal women. [4] [5] Menotropins were successfully introduced into clinical use by Bruno Lunenfeld in 1961. [4] While earlier menotropin medications contained FSH and LH at a 1:1 ratio, the recognition that it is FSH that is critical for follicle stimulation has led to development of newer preparations that contain a much higher FSH/LH ratio, Fertinex being an example. [4]

Menotropin preparations are designed for use in selected women where they stimulate the ovaries to mature follicles, thus making them more fertile. They are administered by typically daily injection, intramuscularly or subcutaneously, for about ten days under close supervision to adjust dose and duration of therapy. They can also be used in hypogonadal men to stimulate sperm production.

Human urinary-derived menotropin preparations are exposed to the theoretical risk of infection from menopausal donors of urine. Nevertheless, the failure to irrefutably demonstrate infectivity following intracerebral inoculation with urine from transmissible spongiform encephalopathy (TSE)-infected hosts suggests that the risk associated with products derived from urine is merely theoretical. [6]

Recombinant gonadotropins have to a large degree replaced hMG in fertility treatments. The recombinant process allows for the production of pure FSH or LH not "contaminated" by other proteins that may be present after urinary extraction. While some head-on studies seem not to suggest that "pure FSH" gives better results than hMG, [7] others claim that recombinant FSH is more efficient and reduces costs. [8] A Cochrane Collaboration analysis did not reveal major differences in clinical outcomes when comparing urinary versus recombinant FSH. [9]

The Practice Committee of the American Society for Reproductive Medicine reported: [10] “Compared with earlier crude animal extracts, modern highly purified urinary and recombinant gonadotropin products have clearly superior quality, specific activity, and performance. There are no confirmed differences in safety, purity, or clinical efficacy among the various available urinary or recombinant gonadotropin products.”

List of hMG preparations

A number of drug companies have and had marketed hMG preparations that include: [11]

Highly purified urinary FSH and LH in 1:1 ratio
highly purified urinary FSH and LH in 1:1 ratio
highly purified urinary FSH
Pergonal was the major hMG prior to the arrival of recombinant gonadotropins containing 75 IU FSH and 75 IU LH.

See also

Related Research Articles

<span class="mw-page-title-main">Gonad</span> Gland that produces sex cells

A gonad,sex gland, or reproductive gland is a mixed gland that produces the gametes and sex hormones of an organism. Female reproductive cells are egg cells, and male reproductive cells are sperm. The male gonad, the testicle, produces sperm in the form of spermatozoa. The female gonad, the ovary, produces egg cells. Both of these gametes are haploid cells. Some hermaphroditic animals have a type of gonad called an ovotestis.

<span class="mw-page-title-main">Menstrual cycle</span> Natural changes in the human female reproductive system

The menstrual cycle is a series of natural changes in hormone production and the structures of the uterus and ovaries of the female reproductive system that makes pregnancy possible. The ovarian cycle controls the production and release of eggs and the cyclic release of estrogen and progesterone. The uterine cycle governs the preparation and maintenance of the lining of the uterus (womb) to receive an embryo. These cycles are concurrent and coordinated, normally last between 21 and 35 days, with a median length of 28 days, and continue for about 30–45 years.

Luteinizing hormone is a hormone produced by gonadotropic cells in the anterior pituitary gland. The production of LH is regulated by gonadotropin-releasing hormone (GnRH) from the hypothalamus. In females, an acute rise of LH known as an LH surge, triggers ovulation and development of the corpus luteum. In males, where LH had also been called interstitial cell–stimulating hormone (ICSH), it stimulates Leydig cell production of testosterone. It acts synergistically with follicle-stimulating hormone (FSH).

<span class="mw-page-title-main">Human chorionic gonadotropin</span> Hormone

Human chorionic gonadotropin (hCG) is a hormone for the maternal recognition of pregnancy produced by trophoblast cells that are surrounding a growing embryo, which eventually forms the placenta after implantation. The presence of hCG is detected in some pregnancy tests. Some cancerous tumors produce this hormone; therefore, elevated levels measured when the patient is not pregnant may lead to a cancer diagnosis and, if high enough, paraneoplastic syndromes, however, it is not known whether this production is a contributing cause, or an effect of carcinogenesis. The pituitary analog of hCG, known as luteinizing hormone (LH), is produced in the pituitary gland of males and females of all ages.

<span class="mw-page-title-main">Follicle-stimulating hormone</span> Gonadotropin that regulates the development of reproductive processes

Follicle-stimulating hormone (FSH) is a gonadotropin, a glycoprotein polypeptide hormone. FSH is synthesized and secreted by the gonadotropic cells of the anterior pituitary gland and regulates the development, growth, pubertal maturation, and reproductive processes of the body. FSH and luteinizing hormone (LH) work together in the reproductive system.

<span class="mw-page-title-main">Gonadotropin-releasing hormone</span> Mammalian protein found in Homo sapiens

Gonadotropin-releasing hormone (GnRH) is a releasing hormone responsible for the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary. GnRH is a tropic peptide hormone synthesized and released from GnRH neurons within the hypothalamus. The peptide belongs to gonadotropin-releasing hormone family. It constitutes the initial step in the hypothalamic–pituitary–gonadal axis.

Gonadotropins are glycoprotein hormones secreted by gonadotropic cells of the anterior pituitary of vertebrates. This family includes the mammalian hormones follicle-stimulating hormone (FSH) and luteinizing hormone (LH), the placental/chorionic gonadotropins, human chorionic gonadotropin (hCG) and equine chorionic gonadotropin (eCG), as well as at least two forms of fish gonadotropins. These hormones are central to the complex endocrine system that regulates normal growth, sexual development, and reproductive function. LH and FSH are secreted by the anterior pituitary gland, while hCG and eCG are secreted by the placenta in pregnant humans and mares, respectively. The gonadotropins act on the gonads, controlling gamete and sex hormone production.

Fertility medications, also known as fertility drugs, are medications which enhance reproductive fertility. For women, fertility medication is used to stimulate follicle development of the ovary. There are very few fertility medication options available for men.

<span class="mw-page-title-main">Folliculogenesis</span> Process of maturation of primordial follicles

In biology, folliculogenesis is the maturation of the ovarian follicle, a densely packed shell of somatic cells that contains an immature oocyte. Folliculogenesis describes the progression of a number of small primordial follicles into large preovulatory follicles that occurs in part during the menstrual cycle.

<span class="mw-page-title-main">Hypothalamic–pituitary–gonadal axis</span> Concept of regarding the hypothalamus, pituitary gland and gonadal glands as a single entity

The hypothalamic–pituitary–gonadal axis refers to the hypothalamus, pituitary gland, and gonadal glands as if these individual endocrine glands were a single entity. Because these glands often act in concert, physiologists and endocrinologists find it convenient and descriptive to speak of them as a single system.

<span class="mw-page-title-main">Follicular phase</span> Phase of the estrous or menstrual cycle

The follicular phase, also known as the preovulatory phase or proliferative phase, is the phase of the estrous cycle during which follicles in the ovary mature from primary follicle to a fully mature graafian follicle. It ends with ovulation. The main hormones controlling this stage are secretion of gonadotropin-releasing hormones, which are follicle-stimulating hormones and luteinising hormones. They are released by pulsatile secretion. The duration of the follicular phase can differ depending on the length of the menstrual cycle, while the luteal phase is usually stable, does not really change and lasts 14 days.

Ovulation induction is the stimulation of ovulation by medication. It is usually used in the sense of stimulation of the development of ovarian follicles to reverse anovulation or oligoovulation.

<span class="mw-page-title-main">Cetrorelix</span> Drug used in IVF procedures

Cetrorelix, or cetrorelix acetate, sold under the brand name Cetrotide, is an injectable gonadotropin-releasing hormone (GnRH) antagonist. A synthetic decapeptide, it is used in assisted reproduction to inhibit premature luteinizing hormone surges The drug works by blocking the action of GnRH upon the pituitary, thus rapidly suppressing the production and action of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). In addition, cetrorelix can be used to treat hormone-sensitive cancers of the prostate and breast and some benign gynaecological disorders. It is administered as either multiple 0.25 mg daily subcutaneous injections or as a single-dose 3 mg subcutaneous injection. The duration of the 3 mg single dose is four days; if human chorionic gonadotropin (hCG) is not administered within four days, a daily 0.25 mg dose is started and continued until hCG is administered.

Controlled ovarian hyperstimulation is a technique used in assisted reproduction involving the use of fertility medications to induce ovulation by multiple ovarian follicles. These multiple follicles can be taken out by oocyte retrieval for use in in vitro fertilisation (IVF), or be given time to ovulate, resulting in superovulation which is the ovulation of a larger-than-normal number of eggs, generally in the sense of at least two. When ovulated follicles are fertilised in vivo, whether by natural or artificial insemination, there is a very high risk of a multiple pregnancy.

<span class="mw-page-title-main">In vitro maturation</span> Artificial maturation of harvested immature egg cells

In vitro maturation (IVM) is the technique of letting the contents of ovarian follicles and the oocytes inside mature in vitro. It can be offered to women with infertility problems, combined with In Vitro Fertilization (IVF), offering women pregnancy without ovarian stimulation.

Poor ovarian reserve is a condition of low fertility characterized by 1): low numbers of remaining oocytes in the ovaries or 2) possibly impaired preantral oocyte development or recruitment. Recent research suggests that premature ovarian aging and premature ovarian failure may represent a continuum of premature ovarian senescence. It is usually accompanied by high FSH levels.

Gonadotropin preparations are drugs that mimic the physiological effects of gonadotropins, used therapeutically mainly as fertility medication for ovarian hyperstimulation and ovulation induction. For example, the so-called menotropins consist of LH and FSH extracted from human urine from menopausal women. There are also recombinant variants.

Infertility in polycystic ovary disease (PCOS) is a hormonal imbalance in women that is thought to be one of the leading causes of female infertility. Polycystic ovary syndrome causes more than 75% of cases of anovulatory infertility.

Carl Axel Gemzell was a Swedish medical doctor and pioneer in reproductive endocrinology.

Gonadotropin surge-attenuating factor (GnSAF) is a nonsteroidal ovarian hormone produced by the granulosa cells of small antral ovarian follicles in females. GnSAF is involved in regulating the secretion of luteinizing hormone (LH) from the anterior pituitary and the ovarian cycle. During the early to mid-follicular phase of the ovarian cycle, GnSAF acts on the anterior pituitary to attenuate LH release, limiting the secretion of LH to only basal levels. At the transition between follicular and luteal phase, GnSAF bioactivity declines sufficiently to permit LH secretion above basal levels, resulting in the mid-cycle LH surge that initiates ovulation. In normally ovulating women, the LH surge only occurs when the oocyte is mature and ready for extrusion. GnSAF bioactivity is responsible for the synchronised, biphasic nature of LH secretion.

References

  1. 1 2 van de Weijer BH, Mulders JW, Bos ES, Verhaert PD, van den Hooven HW (November 2003). "Compositional analyses of a human menopausal gonadotrophin preparation extracted from urine (menotropin). Identification of some of its major impurities". Reproductive Biomedicine Online. 7 (5): 547–557. doi: 10.1016/S1472-6483(10)62071-8 . PMID   14680547.
  2. Menotropins at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
  3. TheFreeDictionary > Menotropin Citing: Dorland's Medical Dictionary for Health Consumers. 2007
  4. 1 2 3 4 Lunenfeld B (2004). "Historical perspectives in gonadotrophin therapy". Human Reproduction Update. 10 (6): 453–467. doi: 10.1093/humupd/dmh044 . PMID   15388674.
  5. Unknown. "Serono goes recombinant". Serono Laboratories, 2011. Archived from the original on 2013-12-02. Retrieved 2013-11-24.
  6. Reichl H, Balen A, Jansen CA (October 2002). "Prion transmission in blood and urine: what are the implications for recombinant and urinary-derived gonadotrophins?". Human Reproduction. 17 (10): 2501–2508. doi:10.1093/humrep/17.10.2501. PMID   12351519.
  7. Bagratee JS, Lockwood G, López Bernal A, Barlow DH, Ledger WL (February 1998). "Comparison of highly purified FSH (metrodin-high purity) with pergonal for IVF superovulation". Journal of Assisted Reproduction and Genetics. 15 (2): 65–69. doi:10.1007/BF02766827. PMC   3455420 . PMID   9513843.
  8. Daya S, Ledger W, Auray JP, Duru G, Silverberg K, Wikland M, et al. (December 2001). "Cost-effectiveness modelling of recombinant FSH versus urinary FSH in assisted reproduction techniques in the UK". Human Reproduction. 16 (12): 2563–2569. doi: 10.1093/humrep/16.12.2563 . PMID   11726575.
  9. van Wely M, Kwan I, Burt AL, Thomas J, Vail A, Van der Veen F, Al-Inany HG (February 2011). Van Wely M (ed.). "Recombinant versus urinary gonadotrophin for ovarian stimulation in assisted reproductive technology cycles". The Cochrane Database of Systematic Reviews. 2011 (2): CD005354. doi:10.1002/14651858.CD005354.pub2. PMC   7388278 . PMID   21328276.
  10. Practice Committee of American Society for Reproductive Medicine, Birmingham, Alabama (November 2008). "Gonadotropin preparations: past, present, and future perspectives". Fertility and Sterility. 90 (5 Suppl): S13–S20. doi: 10.1016/j.fertnstert.2008.08.031 . PMID   19007609.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  11. Fuller MA, Sajatovic M (2003). Drug Information Handbook for Psychiatry (4 ed.). Lexi-Comp, Inc. p. 711. ISBN   978-1-59195-064-6.