Double-Blind, Placebo-Controlled Trial of Cyproterone Acetate to Prevent Flare-Up Effect on Dogs Implanted With Deslorelin

Deslorelin slow-released implants are registered in Europe for the reversible suppression of fertility in male dogs. After administration, a time-limited increase in sex hormones concentration and related behavioral problems may be observed. The aim of this work was to assess whether cyproterone acetate, a synthetic progestogen, can prevent this flare-up effect. Eighteen privately-owned entire male dogs were enrolled in this double-blind, placebo-controlled, randomized clinical trial. All subjects received a 4.7 mg deslorelin implant by SC route and 1–3 capsules containing either cyproterone acetate 2 mg/kg (N = 9) or a placebo (N = 9), by oral route BID for 14 days, depending on the dog's weight. The dogs were followed for 28 days. An increase in the blood testosterone concentration was observed in respectively 9/9 and 7/9 dogs of the control and cyproterone groups (p = 0.47). However, a worsening of the sex hormone related problems (i.e., urinary marking, mounting, aggressiveness toward other dogs and/or escape) was only observed in the placebo group, in 56 or 66% of the dogs as measured by respectively the veterinarian and the owners. Our study suggests that cyproterone acetate is effective and safe to supress the deslorelin induced behavioral flare-up effect, but not the rise in testosterone.

Underlying Breast Cancer Risk and Menopausal Hormone Therapy

The recent Collaborative Group on Hormonal Factors in Breast Cancer (CGHFBC) publication calculated the attributable risk of breast cancer from use of estrogen alone and estrogen plus a synthetic progestogen for less than 5 to 15 or more years of use. This CGHFB report calculated attributable risk based on their findings of relative risk from pooled data from 58 studies. Notably, neither the CGHFBC nor other previous studies have examined the effect of underlying risk of breast cancer on attributable risk. This omission prompted us to determine the magnitude of the effect of underlying risk on attributable risk in this perspective. Meaningful communication of the potential risk of menopausal hormonal therapy requires providing women with the estimated risk above their existing underlying risk (ie, attributable risk). Therefore, we have estimated attributable risks from the data published by the CGHFBC, taking into account varying degrees of underlying risk. Based on the Endocrine Society Guideline on Menopausal Hormone Therapy (MHT), we divided groups into 3 categories of risk: low (1.5%), intermediate (3.0%), and high (6.0%) underlying risk of breast cancer over 5 years. In women taking estrogen plus a synthetic progestogen for 5 to 9 years, the attributable risks of MHT increased from 12, to 42, to 85 additional women per 1000 in the low-, intermediate-, and high-risk groups, respectively. The attributable risks for estrogen alone were lower but also increased based on underlying risk. Notably, the attributable risks were amplified with duration of MHT use, which increased both relative risk and breast cancer incidence.

Oral Allylestrenol: A Pregnancy-supporting Progestogen

ABSTRACT Allylestrenol is a synthetic progestogen that has been in therapeutic use in the management of mild to severe cases of certain obstetric complications, like selected forms of miscarriage/abortion, threatened preterm labor, intrauterine growth restriction (IUGR), and gestational hypertension. Natural progesterone may be used for treatment; however, it has the property of being rapidly metabolized in the liver besides having little or no oral activity. While there are many other synthetic and orally administrable progesterone analogs in the market, most of them, which are 19-nortestosterone derivatives, possess various undesirable side effects like symptoms of intolerance and a tendency to virilization. Allylestrenol, despite being a 19-nortestosterone derivative, has no known side effects including those attributed to the other members of its class, which is theorized to be due to subtle differences in its chemical structure, giving it a unique mechanism of action consisting of a triple effect—trophoblastic, placentotropic, and β2-adrenergic. The present review is mainly aimed at understanding the whys and wherefores behind the molecule's moderate efficacy and remarkable safety along with examining the data from various studies. How to cite this article Malhotra N, Garg R, Malhotra N, Malhotra J. Oral Allylestrenol: A Pregnancy-supporting Progestogen. J South Asian Feder Obst Gynae 2017;9(4):297-303.

The use of a synthetic progesterone, levonorgestrel (LNG), to control the oestrous cycle in the koala

This study investigated the efficacy of a synthetic progestogen, levonorgestrel (LNG), to control koala ovarian activity for the purposes of oestrous synchronisation. Captive koalas were administered either saline control or a 70-mg LNG implant on Day 2 of oestrus. Urogenital cytology, oestrous behaviour and plasma oestradiol-17β and LH concentrations were monitored over a 6-week period. After LNG implant removal females were monitored to determine if the return to oestrus was synchronised. LNG-treated koalas immediately ceased displaying oestrous behaviour, showed no evidence of cornified epithelial cells in smears of urogenital cytology and exhibited low plasma oestradiol-17β concentrations throughout the implantation period. In contrast, oestradiol-17β levels in control koalas showed evidence of continued cyclic activity associated with behavioural oestrus and increased cornified epithelial cells in urogenital smears on Days 33 to 35 after saline injection. After implant removal, LNG-treated koalas exhibited oestrus at 13, 14, 17 and 30 days after implant removal. Plasma LH concentrations varied throughout the study period with no significant time (P = 0.49) or treatment (P = 0.13) effect. Overall results from this study suggest that LNG implants in koalas can inhibit oestrous behaviour and reduce circulating oestradiol-17β levels before oestrus, most likely by preventing development of the pre-ovulatory follicle. However, there was no evidence of LH suppression by the LNG implants. Removal of LNG implants resulted in the synchronous return to oestrus in three of the four treated koalas. Further studies on a larger population are required to validate these findings.

Hormone replacement therapy with estradiol and drospirenone: An overview of the clinical data

A new form of continuous combined hormone replacement therapy has become available that contains estradiol and drospirenone as the progestogen component. Drospirenone is a synthetic progestogen, the only one in hormone replacement therapy in the UK that possesses clinically relevant anti-mineralocorticoid activity. The combination of estradiol and drospirenone has been shown to provide relief from estrogen-deficiency symptoms of the menopause. It also helps to prevent osteoporosis in postmenopausal women by increasing bone density. Further, it has been shown to provide protection against endometrial hyperplasia associated with unopposed estrogen therapy.