Drugs Female Gonadal Hormones and Inhibitors (Linger) Flashcards
(106 cards)
principal function of FSH
direct ovarian follicle development
primary regulatory of spermatogenesis
in males, role of LH
main stimulus for the synthesis of testosterone from cholesterol by Leydig cells
what are the clinical uses of FSH, LH and HCG
used in states of infertility to stimulate spermatogenesis in men and to induce ovulation in women
ii) Most common use is for controlled ovulation hyperstimulation, a key step of assisted reproductive technologies (ART) such as in vitro fertilization (IVF)
what receptors do LH, FSH, and HCG activate
GPCR’s
clincal use of menotropins (human menopausal gonadotropins or hMG)
(a) Used in conjunction with hCG to induce ovulation and pregnancy in infertile females experiencing anovulation not caused by primary ovarian failure
(b) Stimulation of multiple follicle development in ovulatory patients as part of an ART
(c) Unlabeled: Stimulation of spermatogenesis in hypogonadotropic hypogonadism
Follitropin alfa
follitropin beta
urofollitropin
FSH
clinical use of rFSH, uFSH
(a) Ovulation induction in patients who previously received pituitary suppression (uFSH)
(b) Ovulation induction in patients in whom the cause of infertility is functional and not caused by primary ovarian failure (rFSH alfa and beta)
(c) Spermatogenesis induction in men with hypogonadotropic hypogonadism in whom the cause of infertility is not due to primary testicular failure (rFSH alfa and beta)
(d) Development of multiple follicles with ART (uFSH, rFSH alfa and beta)
lutropin alpha
LH
clinical use of lutropin alfa
only used in combination with rFSH alfa for stimulation of follicular development in infertile women with profound LH deficiency
what is the clinical use of extracted hCG
(a) Extracted hCG is used to induce ovulation and pregnancy in anovulatory, infertile females; treatment of hypogonadotropic hypogonadism, spermatogenesis induction with rFSH
what is the clinical use of rhCG
(b) rhCG induces ovulation in infertile females who have been pretreated with follicle stimulating hormones; induces ovulation and pregnancy in infertile females when the cause of infertility is functional
what are the adverse effects of gonadotropins (LH and FSH ) and HCG
(1) Multiple pregnancies
(a) Risk of multiple pregnancy is 15-20% in ART patients (1% in the general population)
(b) Multiple pregnancies increase the risk for gestational diabetes, preeclampsia, and preterm labor
(2) Overstimulation of the ovary during ovulation induction often leads to uncomplicated ovarian enlargement that usually resolves spontaneously
(3) Ovarian hyperstimulation syndrome
(a) Occurs in 0.5-4% of patients
(b) Characterized by ovarian enlargement, ascites, hydrothorax, and hypovolemia, sometimes resulting in shock
Leuprolide
prototype GnRH analog
Goserelin Histrelin Nafarelin Triptorelin Gonadorelin
GnRH analogs
gonadorelin is a synthetic human GnRH
what is the outcome of continuous administration of gonadorelin and leuprolide or other analogs
biphasic response!
first 7-10 days—> agonist effect with increased concentrations of gonadal hormones (flare)
after first 7-10 days–> inhibitory action that manifests as a drop in the concentration of gonadotropins and gonadal steroids (due to receptor down -regulation and changes in the signaling pathways activated by GnRH)
what are the clinical uses of GnRH analogs where stimulation of gonadotropin production is useful ?
female and male infertility
diagnosis of LH responsiveness –> determines whether delayed puberty in a hypogonadotropic adolescent is due to constitutional delay or to hypogonadotropic hypogonadism
what are the clinical uses of GnRH analogs where suppression of gonadotropin production is useful
Controlled ovarian hyperstimulation
endometriosis
uterine leiomyomata (benign estrogen sensitive uterine fibroids) (treatment may reduce size
prostate cancer
central precocious puberty
continuous treatment of women with GnRH analog can cause what typical symptoms
menopausal symptoms- hot flashes, sweats, headaches
- depression, diminished libido, generalized pain, vaginal dryness and breast atrophy
- decreased bone density and osteoporosis (long-term use)
ovarian cysts may develop in the first 2 months!
what are the contraindications for use of GnRH analogs
in women who are pregnant and breast-feeding
what does continuous GnRH agonist administration in men cause
hot flushes sweats edema gynecomastia decreased libido decreased hematocrit reduced bone density asthenia
Cetrorelix
Degarelix
Ganirelix
“Lix”
GnRH antagonists
MOA of GnRH antagonist
synthetic competitive antagonists of GnRH receptors inhibit the secretion of FSH and LH in a dose-dependent manner
clinical use of Ganirelix and Cetrorelix
are used to suppress LH surge during controlled ovarian hyperstimulation
clinical use of degarelix
(4) Degarelix is used to treat advanced prostate cancer (GnRH antagonists reduce concentrations of gonadotropins and androgens significantly more rapidly than GnRH agonists and avoids the initial testosterone surge)