Evaluation of safety and effectiveness of gestrinone in the treatment of endometriosis: a systematic review and meta-analysis.

PURPOSE: Endometriosis is a common chronic gynecological disease defined as the presence of endometrial glands and stroma tissue outside the uterus. Gestrinone is an effective antiestrogen that induces endometrial atrophy and/or amenorrhea. The purpose of this systematic review is to provide an evaluation of safety and effectiveness of gestrinone for the treatment of endometriosis. METHODS: We performed a search in six electronic databases: PubMed, MEDLINE (ovid), Embase, Cochrane CENTRAL (clinical trials), Web of Science and Scopus. Our selected primary outcomes were the changes in dysmenorrhea, pain relief including pelvic pain and dyspareunia. The secondary outcomes embrace hormones parameters, pregnancy rate and adverse events. RESULTS: Of 3269 references screened, 16 studies were included involving 1286 women. All studies compared gestrinone with other drugs treatments (placebo, Danazol, Mifepristone tablets, Leuprolide acetate, Quyu Jiedu Recipe) during 6 months. When compared with other drugs treatments, gestrinone relieved dysmenorrhea, pelvic pain, and morphologic response in the ovary. There was an increase on the pregnancy rate. Regarding the side effects observed, gestrinone showed the same adverse events and increased the risk of acne and seborrhea when compared to other treatments. Even if there was any difference in efficacy between gestrinone, danazol, leuprolide acetate, or Quyu Jiedu Recipe Chinese Medicine, it remains unclear due to insufficient data. CONCLUSION: Based limited evidence available suggests that gestrinone appeared to be safe and may have some efficacy advantages over danazol, as well as other therapeutic interventions for treating endometriosis. However, this conclusion should be interpreted with caution, due the quality of the evidence provided is generally very low or unclear. TRIAL REGISTRATION: CRD42021284148.

Progesterone receptor modulators for endometriosis.

BACKGROUND: Endometriosis is defined as the presence of endometrial tissue (glands and stroma) outside the uterine cavity. This condition is oestrogen-dependent and thus is seen primarily during the reproductive years. Owing to their antiproliferative effects in the endometrium, progesterone receptor modulators (PRMs) have been advocated for treatment of endometriosis. OBJECTIVES: To assess the effectiveness and safety of PRMs primarily in terms of pain relief as compared with other treatments or placebo or no treatment in women of reproductive age with endometriosis. SEARCH METHODS: We searched the following electronic databases, trial registers, and websites: the Cochrane Gynaecology and Fertility Group (CGFG) Specialised Register of Controlled Trials, the Central Register of Studies Online (CRSO), MEDLINE, Embase, PsycINFO, clinicaltrials.gov, and the World Health Organization (WHO) platform, from inception to 28 November 2016. We handsearched reference lists of articles retrieved by the search. SELECTION CRITERIA: We included randomised controlled trials (RCTs) published in all languages that examined effects of PRMs for treatment of symptomatic endometriosis. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as expected by the Cochrane Collaboration. Primary outcomes included measures of pain and side effects. MAIN RESULTS: We included 10 randomised controlled trials (RCTs) with 960 women. Two RCTs compared mifepristone versus placebo or versus a different dose of mifepristone, one RCT compared asoprisnil versus placebo, one compared ulipristal versus leuprolide acetate, and four compared gestrinone versus danazol, gonadotropin-releasing hormone (GnRH) analogues, or a different dose of gestrinone. The quality of evidence ranged from high to very low. The main limitations were serious risk of bias (associated with poor reporting of methods and high or unclear rates of attrition in most studies), very serious imprecision (associated with low event rates and wide confidence intervals), and indirectness (outcome assessed in a select subgroup of participants). Mifepristone versus placebo One study made this comparison and reported rates of painful symptoms among women who reported symptoms at baseline.At three months, the mifepristone group had lower rates of dysmenorrhoea (odds ratio (OR) 0.08, 95% confidence interval (CI) 0.04 to 0.17; one RCT, n =352; moderate-quality evidence), suggesting that if 40% of women taking placebo experience dysmenorrhoea, then between 3% and 10% of women taking mifepristone will do so. The mifepristone group also had lower rates of dyspareunia (OR 0.23, 95% CI 0.11 to 0.51; one RCT, n = 223; low-quality evidence). However, the mifepristone group had higher rates of side effects: Nearly 90% had amenorrhoea and 24% had hot flushes, although the placebo group reported only one event of each (1%) (high-quality evidence). Evidence was insufficient to show differences in rates of nausea, vomiting, or fatigue, if present. Mifepristone dose comparisons Two studies compared doses of mifepristone and found insufficient evidence to show differences between different doses in terms of effectiveness or safety, if present. However, subgroup analysis of comparisons between mifepristone and placebo suggest that the 2.5 mg dose may be less effective than 5 mg or 10 mg for treating dysmenorrhoea or dyspareunia. Gestrinone comparisons Ons study compared gestrinone with danazol, and another study compared gestrinone with leuprolin.Evidence was insufficient to show differences, if present, between gestrinone and danazol in rate of pain relief (those reporting no or mild pelvic pain) (OR 0.71, 95% CI 0.33 to 1.56; two RCTs, n = 230; very low-quality evidence), dysmenorrhoea (OR 0.72, 95% CI 0.39 to 1.33; two RCTs, n = 214; very low-quality evidence), or dyspareunia (OR 0.83, 95% CI 0.37 to 1.86; two RCTs, n = 222; very low-quality evidence). The gestrinone group had a higher rate of hirsutism (OR 2.63, 95% CI 1.60 to 4.32; two RCTs, n = 302; very low-quality evidence) and a lower rate of decreased breast size (OR 0.62, 95% CI 0.38 to 0.98; two RCTs, n = 302; low-quality evidence). Evidence was insufficient to show differences between groups, if present, in rate of hot flushes (OR 0.79, 95% CI 0.50 to 1.26; two RCTs, n = 302; very low-quality evidence) or acne (OR 1.45, 95% CI 0.90 to 2.33; two RCTs, n = 302; low-quality evidence).When researchers compared gestrinone versus leuprolin through measurements on the 1 to 3 verbal rating scale (lower score denotes benefit), the mean dysmenorrhoea score was higher in the gestrinone group (MD 0.35 points, 95% CI 0.12 to 0.58; one RCT, n = 55; low-quality evidence), but the mean dyspareunia score was lower in this group (MD 0.33 points, 95% CI 0.62 to 0.04; low-quality evidence). The gestrinone group had lower rates of amenorrhoea (OR 0.04, 95% CI 0.01 to 0.38; one RCT, n = 49; low-quality evidence) and hot flushes (OR 0.20, 95% CI 0.06 to 0.63; one study, n = 55; low quality evidence) but higher rates of spotting or bleeding (OR 22.92, 95% CI 2.64 to 198.66; one RCT, n = 49; low-quality evidence).Evidence was insufficient to show differences in effectiveness or safety between different doses of gestrinone, if present. Asoprisnil versus placebo One study (n = 130) made this comparison but did not report data suitable for analysis. Ulipristal versus leuprolide acetate One study (n = 38) made this comparison but did not report data suitable for analysis. AUTHORS' CONCLUSIONS: Among women with endometriosis, moderate-quality evidence shows that mifepristone relieves dysmenorrhoea, and low-quality evidence suggests that this agent relieves dyspareunia, although amenorrhoea and hot flushes are common side effects. Data on dosage were inconclusive, although they suggest that the 2.5 mg dose of mifepristone may be less effective than higher doses. We found insufficient evidence to permit firm conclusions about the safety and effectiveness of other progesterone receptor modulators.

[Research of gestrinone-related abnormal uterine bleeding and the intervention in the treatment: a multi-center, randomized, controlled clinical trial].

OBJECTIVE: To investigate the incidence, influencing factors and intervention of gestrinone-related abnormal uterine bleeding at different dosage of gestrinone in the clinical treatment. METHODS: This was a multicenter, randomized, control study of 195 Chinese women with endometriosis or adenomyosis from June 2011 to November 2013. The subjects were randomized into three groups with oral administration of gestrinone, 2.5 mg dose at one time; twice a week group: 67 cases with oral administration twice a week last three months; double dose first month group: 67 cases with oral administration triple times a week at first month, then twice a week for two months; three times a week group: 61 cases with oral administration three times a week last three months. The improvement of the abnormal uterine bleeding, the changes in estrogen, liver function and blood coagulation were evaluated. At the same time, B-ultrasound examination evaluation were performed. RESULTS: (1) Three months later, the incidence of abnormal uterine bleeding in twice a week group was 30% (20/67), in double dose first month group and three times a week group were 7%(5/67) and 16% (10/61) respectively, there were significant difference between three groups (P<0.05). The incidence in double dose first month group was the most lower. (2) Univariate analysis showed that the dosage and ovarian size were the significant factors for abnormal uterine bleeding (OR=0.461,P= 0.003;OR=0.303,P=0.016); logistic regression analysis demonstrated that the risk of abnormal uterine bleeding in double dose first month group was the lowest when compared with twice a week group and three times a week group, the risk in twice a week group was 5-fold higher than that in double dose first month group (OR=0.211,P=0.011). The incidence of abnormal uterine bleeding in participants with abnormal ovarian volume results from ovarian cyst or ovarian surgery was significantly lower than those with normal ovarian volume (OR=0.304,P=0.018). (3) After the treatment of three months, there were no significant difference in alanine transaminase level between the groups (P>0.05). The body mass index significantly increased in three group (P<0.05), but there were no significant differences between the groups (P>0.05). As for blood coagulation, there were also no significant differences between the groups (P>0.05). CONCLUSIONS: Double dose of gestrinone in the first month could significantly decrease the incidence of gestrinone-related abnormal uterine bleeding. It is a more optimied dosage of gestrinone and without severe side effects. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry, registration number: ChiCTR-TRC-12002327.

Induction of micronuclei in V79 cells by the anabolic doping steroids tetrahydrogestrinone and trenbolone.

The synthetic steroid tetrahydrogestrinone is a new "designer drug" and was recently detected to be illegally used in sports. It is chemically closely related to trenbolone that is known as an animal growth promoter. The potencies of trenbolone, tetrahydrogestrinone and testosterone to induce micronuclei in V79 cells in vitro were determined. CREST analysis was employed to differentiate between aneugenic or clastogenic mechanisms. Cytotoxicity and an influence on the cell cycle were assessed in parallel. Incubations with testosterone, at concentrations between 3 and 300 microM, failed to induce micronuclei. By contrast, tetrahydrogestrinone and trenbolone increased the rate of micronuclei significantly, up to a doubling of the micronuclei rate of untreated controls. Tetrahydrogestrinone and trenbolone displayed a bell-shaped dose-response curve, with maximal effects observed at 3 and 30 microM, respectively. The micronuclei induced by tetrahydrogestrinone and trenbolone were predominantly kinetochor (CREST) positive, pointing to an aneugenic mode of action. This may be related to the specific structure of both molecules with a system of activated double bonds. As the genotoxic effect of tetrahydrogestrinone at a chromosomal level appears at a low concentration range, it cannot be ruled out that tetrahydrogestrinone presents a genotoxic hazard on a chromosomal level under conditions of its current misuse in sports.

Comparative study on the efficacy of Yiweining and Gestrinone for post-operational treatment of stage III endometriosis.

OBJECTIVE: To observe the clinical efficacy and safety of Yiweining (YWN) and gestrinone (GT) in treating post-operational patients of stage III endometriosis (EM-III). METHODS: Fifty-two patients of EM-III after operation were randomly assigned into three groups, the YWN group (20 patients) was treated through oral intake of YWN 200 ml, twice a day; the GT group (19 patients) treated with gestrinone 2.5 mg, twice every week, with the medication starting from the 7th post-operational day and lasting for 6 months. The control group (13 patients) was untreated. Six months was one therapeutic course, and follow-up study was carried out in the 6 - 30 months after the end of the medication. RESULTS: The recurrence rate in the YWN group and the GT group were 5.0% and 5.3% respectively, showing insignificant difference between the two groups, but they were lower than that in the control group (30.7%, P < 0.05). Besides, the adverse reaction rate in the YWN group was lower than that in the GT group (10.0% vs 31.6%, P < 0.05). CONCLUSION: Application of YWN to prevent the post-operational recurrence of endometriosis is effective and safe, and its efficacy is similar to that of GT.

Gestrinone versus danazol as preoperative treatment for hysteroscopic surgery: a prospective, randomized evaluation.

OBJECTIVE: To compare danazol and gestrinone treatment as preoperative endometrial preparation for operative hysteroscopy. DESIGN: Prospective, randomized clinical study. SETTING: University department of gynecological, obstetrical sciences and reproductive medicine. PATIENT(S): One hundred thirty-five patients with endouterine pathologies (endometrial polyps, submucous myoma, septate uterus). INTERVENTION(S): Patients pretreated with gestrinone (n = 68) and with danazol (n = 67) underwent operative hysteroscopy. MAIN OUTCOME MEASURE(S): Endometrial response to the medical pretreatment, side effects, procedure time, intraoperative bleeding, infusion volume, patient satisfaction. RESULT(S): Side effects were infrequent in both groups, though the patients' personal satisfaction was in favor of gestrinone. The rate of endometrial response was higher for the gestrinone group (97.1% vs. 83.6%). Operative time (mean +/- SD) was 12 +/- 1.8 and 15.2 +/- 1.9 minutes for the gestrinone and danazol groups, respectively. The gestrinone group showed a lower incidence of moderate bleeding (3% vs. 22.4%) and a lower infusion volume (2,100 +/- 200 mL vs. 2,400 +/- 250 mL). Regarding cervical dilatation time, no significant difference was found between the two groups (1.6 +/- 0.3 minutes vs. 1.5 +/- 0.4 minutes). CONCLUSION(S): Both treatments are good ways to prepare the endometrium for operative hysteroscopy. However, the data suggest that gestrinone pretreatment is preferable to danazol.

Tetrahydrogestrinone is a potent but unselective binding steroid and affects glucocorticoid signalling in the liver.

Tetrahydrogestrinone (THG) is a steroid recently identified to be misused as doping agent. However, the knowledge on functions of this substance in humans or animal models is rather limited. Therefore, it was our aim to further characterize the pharmacological profile of THG and identify potential adverse side effects. THG was synthesized, the purity was confirmed and its biological activity was tested. The potency of THG to transactivate AR dependent reporter gene expression was two orders of magnitude lower compared to dihydrotestosterone. THG binds with high affinity but unselective to the androgen (AR), progesterone (PR), glucocorticoid (GR) and mineralocorticoid (MR) receptor. Treatment of orchiectomised rats with THG resulted in a stimulation of prostate, seminal vesicle and levator ani muscle, indicating androgenic and anabolic properties. In the liver THG, in contrast to testosteronepropionate (TP), down regulates the expression of the GR dependent tyrosine aminotransferase gene (TAT). In summary, our results demonstrate that THG is not a specific AR agonist. THG exhibits a high binding affinity to all tested steroid hormone receptors and binds with highest affinity to the GR. Our in vivo data are indicative of an anabolic and androgenic potency of THG, but the repression of TAT demonstrates that THG also interferes with the glucocorticoid hormone system. Therefore, it is conceivable that an intake will result in adverse side effects.

Emerging drugs for endometriosis.

Medical treatment of endometriosis relies on drugs that suppress ovarian steroids and induce an hypoestrogenic state that causes atrophy of ectopic endometrium. Gonadotrophin-releasing hormone (GnRH) analogues, danazol, progestogens and oestrogen-progestin combinations have all proven effective in relieving pain and reducing the extent of endometriotic implants. However, symptoms often recur after discontinuation of therapy and hypoestrogenism-related side effects limit the long-term use of most medications. Furthermore, these therapies are of limited value in patients with a desire to become pregnant because they inhibit ovulation. An important target for current research is to identify effective therapies that can be safely administered in the long term. GnRH analogues with add-back therapy, progestogens and continuous oral contraceptive are options available for a medium or long-term systemic treatment. Mifepristone, an antiprogestogen, may constitute an alternative if encouraging preliminary data on its effectiveness and tolerability are confirmed. A very appealing area of interest is the possibility of treating endometriosis without suppressing ovarian function. Aromatase inhibitors might have such characteristics as they have been shown to inhibit oestrogen production selectively in endometriotic lesions, without affecting ovarian function; the clinical role of these drugs in the treatment of endometriosis is under evaluation. Levonorgestrel medicated intrauterine device has proven effective in relieving dysmenorrhoea associated with endometriosis, as well as pain associated with rectovaginal endometriosis. Although a systemic absorption is present determining side effects, this approach is promising in the long-term management of this condition. A fundamental objective of research in endometriosis treatment is to develop new therapeutic approaches based on the findings from experimental studies on the aetiopathogenesis of the disease; current research is focusing on anti-inflammatory drugs and modulators of the immune system. TNF-binding protein-1 and IL-12 have proved effective in reducing endometriotic lesions in animal models, while pentoxifylline and INF-alpha 2b have shown encouraging results in clinical studies. This area may be of paramount importance in the near future in order to develop a therapy that could prevent or eradicate endometriosis rather than merely relieving the symptoms.

Benefits and risks of pharmacological agents used for the treatment of menorrhagia.

Menorrhagia affects the lives of many women. The assessment of menstrual flow is highly subjective and gauging the severity of the condition by objective assessment of menstrual blood loss is impractical. In treating menorrhagia, the primary aim should be to improve quality of life. Women are willing to undergo quite invasive treatment in order to achieve this. Drug therapy is the initial treatment of choice and the only option for those who wish to preserve their reproductive function. Despite the availability of a number of drugs, there is a general lack of an evidence-based approach, marked variation in practice and continuing uncertainty regarding the most appropriate therapy. Adverse effects and problems with compliance also undermine the success of medical treatment. This article reviews the available literature to compare the efficacy and tolerability of different medical treatments for menorrhagia. Tranexamic acid and mefenamic acid are among the most effective first-line drugs used to treat menorrhagia. Despite being used extensively in the past, oral luteal phase norethisterone is probably one of the least effective agents. Women requiring contraception have a choice of the combined oral contraceptive pill, levonorgestrel-releasing intrauterine system (LNG-IUS) or long-acting progestogens. Danazol, gestrinone and gonadotropin-releasing hormone analogues are all effective in terms of reducing menstrual blood loss but adverse effects and costs limit their long-term use. They have a role as second-line drugs for a short period of time in women awaiting surgery. While current evidence suggests that the LNG-IUS is an effective treatment, further evaluation, including long-term follow up, is awaited. Meanwhile, the quest continues for the ideal form of medical treatment for menorrhagia--one that is effective, affordable and acceptable.

Gestrinone versus a gonadotropin-releasing hormone agonist for the treatment of pelvic pain associated with endometriosis: a multicenter, randomized, double-blind study. Gestrinone Italian Study Group.

OBJECTIVES: To evaluate the efficacy of gestrinone versus leuprolide acetate (LA) in improving pelvic pain in women with endometriosis and to compare their effects on bone mineral density and serum lipid profile. DESIGN: Multicenter, double-blind, double-dummy, randomized clinical trial. SETTING: Six academic departments specialized in the study of endometriosis. PATIENT(S): Fifty-five women with moderate or severe pelvic pain and laparoscopically diagnosed endometriosis. INTERVENTION(S): Six-month treatment with oral gestrinone (n = 27) or IM depot LA (n = 28) followed by 6-month follow-up. MAIN OUTCOME MEASURE(S): Variations in severity of dysmenorrhea, deep dyspareunia, and nonmenstrual pain as shown by a visual analog scale and a verbal rating scale, modifications in bone mineral content as shown by dual-roentgenogram absorptiometry, and variations in serum cholesterol subfractions and lipoprotein(a) concentrations. RESULT(S): Significant improvements were observed in all three symptoms considered in both treatment arms. Moderate or severe pain symptoms recurrence on both pain scales was observed in 2 of 17 (11.8%) patients given gestrinone compared with 9 of 17 (52.9%) of those given LA (odds ratio, 0.12; 95% confidence interval, 0.02 to 0.69). Lumbar bone mineral density increased slightly in the gestrinone group but decreased by 3% in the LA one. High-density-lipoprotein cholesterol fell by 25% and lipoprotein(a) decreased by approximately 40% in the gestrinone-treated women but did not vary in those receiving LA. CONCLUSION(S): Oral gestrinone is at least as effective as depot LA for pain relief in women with symptomatic endometriosis. A tendency to prolonged pain reduction was observed after gestrinone compared with LA treatment. Gestrinone does not negatively affect bone density but variations in serum lipids need further evaluation.

Long-term follow-up of endometriosis after two different therapies (Gestrinone and Buserelin).

OBJECTIVE: To compare the efficacy, tolerance and recurrence rate of endometriosis after 5-year follow-up of treatment with Gestrinone and Buserelin, respectively. STUDY DESIGN: A prospective study with randomized follow-up of 5 years duration (minimum) for each patient was done. We included 43 cases of endometriosis diagnosed by laparoscopy or laparotomy and treated them with Gestrinone (Group G, n = 25 cases) or Buserelin intranasal spray (Group B, n = 18) for 6 months. RESULTS: General data: Age, height, weight of patients and AFS score of endometriosis were without significant differences in either group. Specific data: A) Global clinical efficacy was good or excellent in 74% (16/25) of group G and in 78% (14/18) of group B without significant differences. B) Global clinical tolerance was good in 50% of the patients in group G and in 0% in group B (p < 0.001). C) Global evaluation after 5-year follow-up showed "success" only for 36% of patients in group G and in 33% in group B (no significant differences), with "failure" in 40% and 33%, respectively (no significant differences). CONCLUSIONS: 1) Gestrinone and Buserelin intranasal spray are valid treatments for the remission of endometriosis, with "success", "failure" and "clinical recurrence" rates similar after a follow-up of 5 years of initial treatment. 2) The most significant androgenic effect of Gestrinone was the presence of acne. Vascular effects were also considered as very undesirable effects according to the comments of patients. On the contrary, the effects of analogs are generally better tolerated.

Updating the clinical experience in endometriosis--the European perspective.

In a large, double-blind, multicentre study, 269 patients with confirmed endometriosis were randomly allocated to receive either danazol (200 mg twice daily; n = 137) or gestrinone (2.5 mg twice weekly; n = 132) for 6 months. The two groups were comparable in terms of the staging of endometriosis by the American Fertility Society (1979) score. After the sixth month of treatment, repeat laparoscopy was performed. Clinical assessment, haematological and biochemical investigations were carried out during the 6 months of treatment and for a further 12 months' follow-up and are compared between the two groups. A total of 15 patients from the gestrinone group, including four patients with hirsutism, and 17 patients from the danazol group, including six patients with headache, withdrew because of adverse symptoms. An additional 22 patients, including 10 from the gestrinone group and 12 from the danazol group withdrew because of lack of efficacy, pregnancy, elevated hepatic function tests or for reasons unrelated to the trial. Total American Fertility Society scoring showed an improvement of 73.3% in 101 patients receiving gestrinone and 72.7% in 99 patients receiving danazol. The results showed a significant reduction in the severity of dysmenorrhoea by the third month in the danazol group and at 6 months in both groups. There was a significant (P < 0.001) increase in weight observed in both groups during treatment. Overall, the tolerability of danazol and gestrinone was good; however, significantly more patients with gestrinone complained of hirsutism while significantly more with danazol complained of leg cramps. During the 12 months of follow-up, mild, moderate or severe degrees of lower abdominal pain, dysmenorrhoea and deep dyspareunia all fluctuated, with no statistically significant increase in frequency in either group.

Updating the clinical experience in endometriosis--the Brazilian perspective.

In an open-label, multicentre, randomized, parallel group study, 164 women with endometriosis were assigned to treatment. Out of these women, 81 received danazol (600 mg daily for 8 weeks, then 400 mg for 16 weeks) and 83 were given gestrinone (2.5 mg twice a week for 24 weeks). Five weeks before the start of treatment clinical evaluation and diagnostic laparoscopy were performed during the screening visit. Drug assignment and laboratory data assessment were carried out within 3 days of the estimated onset of the menstrual cycle at baseline visit. The response to treatment was assessed during visits at weeks 2, 4, 8, 12, 16, 20 and 24; at the last visit a second laparoscopy was performed. Therapeutic efficacy was evaluated by analysis of the laparoscopic scores assessed according to the revised American Fertility Society classification. Symptomatic response was measured by clinical scores and laboratory data. In one centre, bone mineral density was also recorded. One patient in the danazol group discontinued treatment due to a cutaneous rash as a probable adverse reaction at the beginning of the study. The therapeutic efficacy of danazol and gestrinone did not differ significantly when the revised American Fertility Society scores were compared. The symptomatic response also showed no statistical difference when clinical examination scores were analysed. There was no significant difference between the drugs in laboratory data, including bone mineral density, with respect to adverse events. Analysis of clinical scores showed that danazol was superior to gestrinone with respect to acne and irregular bleeding. Based on these data, we conclude that both danazol and gestrinone are reliable in the treatment of endometriosis and offer similar results.

[Gestrinone in pelvic endometriosis. A one-year evaluation]. / Gestrinona en endometriosis pélvica. Evaluación a unaño.

The therapeutical effectiveness of gestrinone in endometriosis treatment, as well as its long term side effects, were evaluated. Prospective, clinical trial. At "Dr. Alejandro Castanedo Kimball" Hospital (PEMEX). Salamanca, Guanajuato. México. Thirty women with laparoscopically confirmed endometriosis, were studied. Subjects received 2.5 mg. of gestrinone two times per week for 6 months. Laparoscopy was performed before treatment, and clinical response was determined by second laparoscopy after 6 months. The pregnancy rate, frequency of side effects and recurrence of symptoms were determined. Median total endometriosis scores and symptoms decreased significantly after treatment. Four pregnancies were observed after treatment. The principal side effects were: ponderal increase, changes in the voice and hirsutism. However, the side effects disappeared after one year of clinical survey. The results indicate that gestrinone is effective in the treatment of pelvic endometriosis. In despite of a clear benefic effect on stage of the disease and symptoms; the use of gestrinone should weigh the risk-benefit (cost versus metabolic side effects) of treatment.

Gestrinona en endometriosis pélvica. Evaluación a un año / Gestrinone on pelvic endometriosis. Evaluation after one year treatment

Se evaluó la eficacia terapéutica de la gestrinona para el tratamiento de la endometriosis; y los efectos secundarios a largo plazo del fármaco. Estudio clínico prospectivo, Hospital "Dr. Alejandro Castanedo Kimball" (PEMEX), Salamanca, Guanajuato. Treinta mujeres con diagnóstico laparoscópico de endometriosis fueron estudiadas. Las pacientes recibieron tratamiento con gestrinona (2.5 mg. dos veces a la semana, durante 6 meses). Se realizó laparoscopia antes del tratamiento con gestrinona; y la respuesta clínica fue evaluada con otra laparoscopia seis meses después. Se determinó la tas de embarazos; la frecuencia de efectos secundarios y la recurrencia de la sintomatología. Después del tratamiento se observó una mejoría significativa en el grado de la endometriosis; así como en los síntomas referidos por las pacientes. Se obtuvieron cuatro gestaciones después de terminado el tratamiento. Los efectos secundarios más frecuentes fueron: incremento ponderal, cambio en el timbre de la voz e hisutismo; los cuales remitieron en la mayoría de las pacientes después de un año de vigilancia clínica. La gestrinona es un fármaco útil para el tratamiento de la endometriosis, no obstante, su uso debe basarse en la selección cuidadosa de las pacientes y en la valoración del beneficio versus el costo y los efectos metabólicos del medicamento

[Antihormones and laparoscopy in the combined treatment of disseminated forms of genital endometriosis externa]. / Antigormony i laparoskopiia v kombinirovannom lechenii rasprostranennykh form naruzhnogo genital'nogo éndometrioza.

A total of 100 patients with disseminated forms of external genital endometriosis were administered multiple-modality treatment including surgery and antihormone therapy. Twenty patients with the same diagnosis were controls and subjected to surgery alone. The results of treatment assessed on the basis of analysis of the clinical course of the disease, status of the menstrual and generative functions, drug effects on the central nervous system, hormonal status, and target organs (mammary glands and osseous tissue) evidence good potentialities of laparoscopy and high efficacy of subsequent therapy with antihormones in the treatment of patients with grave forms of endometriosis.

Comparative efficacy of gestrinone and danazol in infertile women with endometriosis.

The relationship between endometriosis and infertility is observed frequently. Patients with both conditions require a conservative approach to their management. Since hormonal therapy is one of those approaches, we sought to compare the efficacy of Danazol and Gestrinone in 80 infertile patients (48 and 32, respectively). Therapy lasted 6 months in both treatment groups, and all patients studied had laboratory tests performed and were clinically evaluated and classified through laparoscopy before and after therapy. The improvement of symptoms and favorable follow-up were similar with both treatments. The reestablishment of menstrual patterns and fertility were also nearly alike in both groups. However, Gestrinone was associated with fewer secondary effects and is easier to administer than Danazol. We conclude that Gestrinone is a useful medication in the management of the infertile patient with endometriosis.