Successful induction of ovulation in normogonadotrophic clomiphene resistant anovulatory women by combined naltrexone and clomiphene citrate treatment

Roozenburg, Brigitte J.; Dessel, H.J.H.M. van; Evers, Johannes L.H.; Bots, R. S. G. M.

doi:10.1093/humrep/12.8.1720

Cited by 26 publications

(4 citation statements)

References 9 publications

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“…The increase in LH pulse amplitudes persisted over the entire duration of treatment of 6 months (47) or up to 630 days (11). Even in patients suffering from anovulatory cycles, higher ovulation rates resulted after treatment with naltrexone or naltrexone in combination with clomiphene, versus clomiphene alone (48). After a treatment course of 9 months with daily naltrexone doses of 50-150 mg, Wildt et al reported a per-cycle pregnancy rate of 29% (25).…”

Section: Hypothalamic Amenorrheamentioning

confidence: 99%

Impact of the opioid system on the reproductive axis

Böttcher

Seeber

Leyendecker³

et al. 2017

Fertility and Sterility

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Endogenous opioids, first described more than 40 years ago, have long been recognized for their main role as important neuromodulators within the central nervous system. More recently endogenous opioids and their receptor have been identified in a variety of reproductive and nonreproductive tissues outside the central nervous system. Their role within these tissues and organs, however, is only incompletely understood. In the central nervous system, endogenous opioids inhibit pulsatile GnRH release, in part mediating the stress response within the central nervous-pituitary gonadal axis, resulting in hypothalamic amenorrhea. In the ovary, the presence of endogenous opioids primarily produced by granulosa cells has been demonstrated within the follicular fluid, likely influencing oocyte maturation. In hypothalamic amenorrhea, normal cycles can be restored by the administration of opioid antagonists, such as naltrexone. In polycystic ovarian syndrome, endogenous opioids have found to be elevated and may stimulate insulin secretion from the endocrine pancreas. This effect can be inhibited by opioid antagonists, resulting in a decrease of circulating insulin levels in response to glucose challenge. Endogenous opioids may also play a role in the pathogenesis of ovarian hyperstimulation syndrome. In summary, endogenous opioids exert a wide variety of actions within the reproductive system and are worthy of further scientific study.

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Section: Hypothalamic Amenorrheamentioning

confidence: 99%

Impact of the opioid system on the reproductive axis

Böttcher

Seeber

Leyendecker³

et al. 2017

Fertility and Sterility

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“…A great deal of evidences indicate that hyperinsulinemia, abnormal LH secretion and opioid tone may have a key role in pathophysiologic mechanisms responsible for chronic anovulation in PCOS patients [17,59,60]. Recently we tried to verify whether the benefits of naltrexone in these women could be applied to the clinical management of their infertility [61].…”

Section: Naltrexone Treatment: Implications For the Management Of Pcomentioning

confidence: 99%

Role of Opioid Antagonists in the Treatment of Women with Glucoregulation Abnormalities

Guido¹,

Romualdi²,

Lanzone

2006

CPD

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Beta-endorphin were detected in the endocrine pancreas and seem able to influence insulin and glucagon release. Hence, endogenous opioids could have a role in glucoregulation and in the pathogenesis of obesity beyond the previously detected effects on appetite. Metabolic abnormalities, such as hyperinsulinemia, insulin-resistance and obesity, are common features of polycystic ovary syndrome (PCOS), and seem to have a pathogenetic role in this disorder. A link between opioids and PCOS-related hyperinsulinism is suggested by the finding of altered central opioid tone and elevated beta-endorphins levels, directly correlated with body weight, in these patients. Furthermore, naloxone and naltrexone significantly reduce the insulin response to glucose load only in hyperinsulinemic PCOS patients. This effect is obtained chiefly through an improvement of insulin clearance. Naltrexone is also able to ameliorate the abnormal gonadotrophins secretion and to improve the ovarian responsiveness in obese PCOS women undergoing ovulation induction with exogenous GnRH. Such effects are believed to be obtained through an amelioration of hyperinsulinemia. Gonadal steroids modulate the opioid system both centrally and in peripheral districts. Nevertheless, the decline of ovarian function does not abolish the opioidergic control of glucoregulation. Post-menopausal period is characterised by a high prevalence of hyperinsulinemia and insulin-resistance. In particular, an association between hyperinsulinemia and increased opioid activity was found in postmenopausal women showing a central body fat distribution. Both naloxone and naltrexone ameliorate the metabolic imbalance also when it appears in the climacteric period, and mainly by increasing insulin clearance. The benefits of naltrexone may represent in the future a useful tool for the treatment of women with hyperinsulinism in the clinical practice.

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“…Nevertheless, when clomiphene is given to properly selected women with no other causes of infertility apart from anovulation, cumulative pregnancy rates of Ͼ60% after 6 months and Ͼ90% after 10-12 months have been reported (Hammond et al, 1983;Messinis and Milingos, 1997). Combinations of clomiphene with other drugs, such as naltrexone, in clomiphene resistant patients are also successful (Messinis and Milingos, 1997;Roozenburg et al, 1997). The low risk of the ovarian hyperstimulation syndrome (OHSS) and the low rate of multiple pregnancy during treatment with clomiphene makes it the safest way of treating anovulatory infertility in women belonging to WHO 2363 group II.…”

Section: Monofollicular Developmentmentioning

confidence: 99%