Suppression Of Ovarian Activity Research Articles

Effects of ozone therapy in an experimental murine model of Candida albicans vulvovaginitis

The antifungals used in the treatment of vulvovaginal candidiasis, although effective, can have side effects and high cost, which may not occur with the medicinal use of ozone. The study aimed to evaluate the effects of medicinal home ozone therapy on C. albicans. The experiment was carried out in vitro, cultivating C. albicans in 10mm Petri dishes, containing solid Agar Sabour and Dextrose (Oxoid). The in vivo experiment used 45-day-old female C57/BL6 mice and after suppression of ovarian activity, 20 µL of C. albicans suspension in sterile PBS, at a concentration of 105 yeast cells, were inoculated in a single dose under anesthesia. Distribution occurred in 4 groups: (i) Absolute Control Group (GCA): Not subjected to infection by the pathogen. (ii) Control Group (CG): Submitted to C. albicans infection, but not treated. (iii) Ozone Therapy Group (GO): Subjected to infection and treated with medicinal ozone therapy. (iv) Lavage Group (GL): Subjected to infection and subsequently treated with vaginal lavage. It was found that GC had a higher amount of CFU when compared to GO. Exposure for 600s was able to reduce the number of CFUs by 98.89% when compared to GC. The study concludes that ozone gas showed great efficacy in the proliferation of C. albicans in vitro. The best results were observed with application in liquid medium, however, ozone therapy was able to significantly reduce infection in the experimental model used. In in vivo experiments, the number of CFU/ml found was lower in the ozone-treated group.

Ovarian morphometrical evaluation to assess reproductive activity suppression in heavy weight finishing gilts immunized against gonadotropin-releasing hormone

It is known that immunizing gilts against gonadotropin-releasing hormone (GnRH) is an efficient castration method that increases their growth performance. However, it is still unknown the ovarian histophysiology outcomes after this procedure. Therefore, the aim of this study was to investigate in detail, using morphological and morphometrical methods, changes in the ovarian structure that result in the suppression of ovarian activity, as well as to gain knowledge on the ovarian structure to assist in ovarian histopathological diagnoses. Seventy-two pre-pubertal finishing gilts were allocated to two experimental groups: immunized (IC; n = 36; gilts which received two injections of 2 mL of Vivax® - one at 15 and another at 19 weeks of age) and control (CT; n = 36, females which received two saline injections following the same protocol). All gilts were euthanized at 25 weeks of age and the ovaries of 5 gilts from each experimental group collected for biometrical and histomorphometrical analysis. IC gilts showed higher body weights, but smaller ovaries compared to CT females. In addition, the number of small follicles (≤ 2 mm) on the ovarian surface was higher, while no large follicles (> 6 mm) nor corpora lutea were found in the ovaries of IC gilts. Histomorphometrical analysis revealed that IC females showed higher numbers of quiescent and active primordial, primary, pre-antral and final stage atretic follicles. Moreover, follicle size, antrum diameter and area of the granulosa layer from mature follicles were smaller in IC gilts. Collectively, these results demonstrate that the efficacy of immunization against GnRH is related to the blockage of follicular recruitment and selection, thus suppressing reproductive activity in finishing gilts.

Suppression of ovarian activity in a captive African Lion Panthera leo after deslorelin treatment

Abstract: With the intent to evaluate the efficiency of a contraceptive treatment for cyclic ovarian suppression in African Lionesses Panthera leo using a Gonadotrophin-Releasing Hormone (GnRH) agonist bioimplant, noninvasive fecal steroid assay associated with the observation of the behavioral estrus were employed for a period of 36 months. Five captive adult females, maintained with a vasectomized male, subcutaneously received a 9.4mg deslorelin acetate implant. The treatment initially stimulated behavioral estrus along with ovarian activity, demonstrated by an estrogen increase in two lionesses. A rise in progesterone concentration in two other animals suggested possible treatment-induced ovulation. After the initial period, deslorelin prevented ovarian activity for at least 22 months. Two females exhibited signs of behavioral estrus after 22 and 31 months. A third lioness with an increased estrogen concentration did not exhibit behavioral estrus signs or a consequent progesterone surge until 33 months after implantation, suggesting a possible resumption of ovarian activity. One female did not exhibit any behavioral estrus signs nor a rise in steroid levels after the “treatment-induced” estrus throughout the entire experiment (36 months). One lioness died after 15 months without exhibiting signs of estrus or an increased progesterone level, however, the estrogen concentration increased 12 months post-implantation, suggesting resumed ovarian activity. The study showed that long-term treatment with a GnRH agonist can be extremely effective as a contraceptive treatment in African lionesses, however, the duration of contraception may vary among individuals and may bear the risk of permanent loss of normal ovarian activity.

Ovarian protection with gonadotropin-releasing hormone agonists during cyclophosphamide therapy in systemic lupus erythematosus.

Administration of cyclophosphamide (CYC), an alkylating agent used to treat malignancies and severe rheumatic diseases, creates a risk of ovarian insufficiency that is related to the intensity and duration of therapy and the age of the patient. To preserve reproductive capacity in the appropriate clinical setting, oocyte, embryo, and/or ovarian tissue cryopreservation are recommended. Medical protection with depot gonadotropin-releasing hormone agonists (GNRHa) has emerged as a potential means to preserve both fertility and ovarian function through the suppression of ovarian activity during treatment with alkylators. We review the trials of GNRHa for ovarian protection in both cancer and rheumatic disease patients. Trials in cancer patients receiving CYC alone, or in combination with other gonadotoxic agents that have employed several different GNRHa have yielded mixed results. Trials in lupus patients receiving lower doses of CYC alone utilizing depot leuprolide acetate have tended to show favorable results.

EP31.08: Does hormonal status influence uterine venous diameter?

Pelvic venous congestion (PVC) primarily affects premenopausal (Pre-M) women and is characterised by evidence of pelvic varicosities on transvaginal ultrasound (TVS). Postmenopausal (Po-M) women rarely exhibit these symptoms suggesting that hormonal influence is a definite factor. The aim of this study was to examine the affect hormonal status has on vein diameter. This was a single-centre, prospective cross-sectional study of women attending our general gynecology clinic during a 16-month period. Demographic data and a full medical/surgical history were recorded. Exclusion criteria included age<18 years, previous hysterectomy, contraindication to/declining TVS and evidence of pelvic pathology on TVS. All women underwent TVS assessment of the pelvic organs and pelvic veins. The Mann Whitney U-test was used to compare the diameters between Pre-M and Po-M women. Linear regression was performed to examine whether exogenous hormone use influenced venous diameter. 486 women had normal pelvic organs out of 1500 women examined. Of these, 375 were Pre-M and 111 were Po-M. Overall, the pelvic vessel diameters were smaller in Po-M women, with statistical significance observed in the right vein and both sides combined. Exogenous hormone use in the Pre-M group was associated with smaller vessel diameters, with statistical significance in the left vein (p = 0.001). There was no association between vein diameter and HRT use in the Po-M group (p = 0.98 left vein; p = 0.64 right vein). Our findings showed that Pre-M women have larger pelvic veins than Po-M women. These findings provide further insight into the biomechanics of veins and hence suggest that they are sensitive to hormonal fluctuations. This is further supported by our findings revealing that suppression of ovarian activity with hormones in Pre-M women leads to a reduction in vein diameter, which is often treatment for PVC. EP31.08: Table 1. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Rationale for eliminating the hormone-free interval in modern oral contraceptives.

Although most low-dose combined oral contraceptives (COCs) include 7-day hormone-free intervals (HFIs), these COCs could incompletely suppress ovarian activity. To review the impact of HFIs on ovarian suppression and tolerability, and evaluate the utility of COCs without traditional 7-day HFIs. PubMed was searched for clinical studies published in English between January 1980 and April 2015 on the impact of HFIs and HFI modifications in COCs. Articles assessing contraceptive efficacy or tolerability as the primary focus were included. Abstracts of 319 articles were screened. Analysis of the 161 articles selected revealed that suppression of ovarian activity with low-dose COCs with 7-day HFIs is suboptimal. Loss of ovarian suppression during 7-day HFIs is commonly associated with follicular development, and most dominant follicles appear during this period. By contrast, increased ovarian suppression was noted in regimens that shortened or eliminated the HFI, or that substituted low-dose ethinyl estradiol for the HFI. Extended regimens with modified HFIs may provide greater ovarian suppression with the potential for increased contraceptive effectiveness. Additional research is needed to evaluate whether COC regimens that include 10μg ethinyl estradiol instead of an HFI may improve tolerability.

Suppression of ovarian activity with a low-dose 21/7-day regimen oral contraceptive containing ethinylestradiol 20 mcg/drospirenone 3 mg in Japanese and Caucasian women

BackgroundTwo studies assessed the effect of a low-estrogen-dose 21/7-day oral contraceptive containing ethinylestradiol and drospirenone (EE 20 mcg/drsp 3 mg) on ovarian activity in Japanese and Caucasian women. Study DesignStudy 1 was conducted in Japanese women (20–35 years), and Study 2 was conducted in Caucasian women (18–35 years). All women received EE 20 mcg/drsp 3 mg in a 21-day active pill regimen. The primary endpoint was the proportion of women with ovulation inhibition (Hoogland score <6; as assessed by transvaginal ultrasonography) during treatment cycle 2. ResultsJapanese (n=23) and Caucasian (n=30) women received two cycles of study treatment. During treatment cycle 2, ovulation was inhibited in 100% and 92.9% of Japanese and Caucasian women, respectively. ConclusionsEE 20 mcg/drsp 3 mg in a 21/7-day regimen provides comparable ovarian suppression in Japanese and Caucasian women, with normal ovarian function resuming shortly after treatment end in both populations.

Contraception and gynaecological care

Hormonal contraception, through suppression of ovarian activity or endometrial proliferation, can be used to treat and prevent a range of gynaecological disorders. There is evidence to support the effectiveness of the levonorgestrel intra-uterine system (LNG-IUS), combined oral contraceptive pill (COC) and progestogen-only injectable depot-medroxyprogesterone acetate for treating heavy menstrual bleeding and dysmenorrhoea. COCs are also an effective treatment for acne and hirsuitism, and may lessen the symptoms of premenstrual syndrome. There is good evidence that COCs can significantly reduce the risk of both ovarian and endometrial cancer. There is also some evidence that COCs may prevent ovarian cysts, endometrial hyperplasia and fibroids. The LNG-IUS may be used as endometrial protection in women using hormone replacement therapy or tamoxifen. This chapter will deal with the evidence for both treatment and prevention of a range of gynaecological disorders of different hormonal contraceptive methods.

Suppression of ovarian activity with a drospirenone-containing oral contraceptive in a 24/4 regimen

BackgroundThis study was conducted to compare ovarian activity of an oral contraceptive containing drospirenone (drsp) 3 mg plus ethinylestradiol (EE) 20 mcg administered in 24/4 regimen compared with the conventional 21/7 regimen, during intended use and following predefined dosing errors. Study designWomen aged 18–35 years who ovulated or had a follicular diameter of ≥15 mm on or before Day 23 during a pretreatment cycle were admitted into this double-blind, randomized study. Participants underwent 3 treatment cycles with drsp 3 mg/EE 20 mcg in a 24/4 (n=52) or a 21/7 (n=52) regimen. In the third treatment cycle, the initial three pills in both groups were replaced with placebos. Ovarian activity was classified using the Hoogland scale during pretreatment and during Cycles 2 and 3. ResultsSuppression of ovarian activity was more pronounced with the 24/4 regimen — the odds ratio for a lower Hoogland score (i.e., greater ovarian suppression) with the 24/4 regimen compared with the conventional 21/7 regimen were 6.01 (95% CI: 2.29–17.94) and 3.06 (95% CI: 1.44–6.65) for Cycles 2 and 3, respectively. More women in the 24/4 regimen group had no ovarian activity 87.8% vs. 56.0% during Cycle 2 and 55.1% vs. 30.0% during Cycle 3. The 24/4 regimen was associated with a more consistent suppression (less fluctuation) of endogenous estradiol. ConclusionThe drsp 3 mg/EE 20 mcg oral contraceptive in a 24/4 regimen was associated with greater ovarian suppression (despite intentional dosing error), which results in decreased hormonal fluctuations, and may increase contraceptive efficacy with the low-dose formulation.

Different ovarian responses to potential mates underlie species-specific breeding strategies in common marmoset and Goeldi's monkey

Callitrichids are cooperative breeders, characterized by obligate twinning, extensive paternal care, and monopolization of reproduction by the dominant female. This is the case in the common marmoset, and in common marmoset groups of more than one adult female, subordinate females are typically acyclic consistent with infertility. However, one callitrichid, Goeldi's monkey, gives birth to singletons and exhibits low paternal care. Given these reproductive traits of Goeldi's monkey, we hypothesized that there would not be suppression of ovarian activity. To test this hypothesis, we applied non-invasive endocrine methods in a step-wise experiment with laboratory groups of both species. In each species, six pairs of sisters were studied alone, in visual contact with an unrelated male and in a polygynous trio with the male, and urine samples were collected for determination of oestrogen titres reflecting ovarian activity. Common marmoset sister pairs exhibited a marked difference in social status: during the study 5 of 6 dominant females conceived but only 1 of 6 subordinate females; the remaining 5 subordinates were acyclic at the end of the study, and instances of ovulation typically resulted in aggression. Goeldi's monkey sister pairs showed no status differences: in all pairs, however, both sisters exhibited a temporary cessation of ovarian cyclicity on trio formation, followed by ovulation and conception. We conclude that these marked differences in ovarian responses reflect the differences in inter-female competition for paternal caregiving resources. In common marmosets with high inter-female competition, suppression of ovulation functions to reduce aggression received by subordinate females; in Goeldi's monkey with low competition, temporary cessation of ovulation could facilitate female choice.

Therapeutic Effect of Angiostatin Gene Transfer in a Murine Model of Endometriosis

Endometriosis, the growth of ectopic endometrial tissue, is a chronic recurrent disease affecting 10% of the female population causing dyspareunia, pelvic pain, dysmenorrhea, and infertility. Suppression of ovarian activity is the cornerstone of medical therapy with limited benefit and severe adverse effects. Angiogenesis plays a major role in the development of endometriosis suggesting that anti-angiogenic therapy would offer a new therapeutic approach. We report successful treatment of endometriosis in estrogen-supplemented ovariectomized mice by transient overexpression (6 to 10 days of duration) of the gene for a natural angiogenesis inhibitor angiostatin, delivered to the peritoneum by a replication-deficient adenovirus vector (AdAngiostatin). Established endometriosis was eradicated in 14 of 14 AdAngiostatin-treated animals, whereas 11 of 13 control animals showed full disease development. Administered to normal cycling mice for the same transient period, AdAngiostatin caused impaired ovarian function with suppressed corpus luteum development, decreased production of estradiol and progesterone, decreased ovarian and uterine weight, and increased body weight. AdAngiostatin treatment lowered the levels of sex steroids but did not induce total castration. Gene therapy with angiogenic inhibitors is a highly effective treatment for endometriosis, even in a host with preserved estrogen levels. However, local or targeted delivery of the gene must be considered to avoid prolonged systemic effects and impaired ovarian function.

Depot versus daily administration of gonadotrophin releasing hormone agonist protocols for pituitary desensitization in assisted reproduction cycles.

Gonadotrophin-releasing hormone agonist (GnRHa) has been widely used in cycles of in vitro fertilization (IVF). Among the various types of GnRHa ovarian stimulation protocols, the long protocol presents the best clinical pregnancy rates per cycle initiated (GnRHa administration until the suppression of ovarian activity is evident, within approximately 14 days). There are two types of GnRHa administration that can be used to lead to hypophysis desensitization in the IVF cycle in the long protocol: one consisting of daily GnRHa low doses, and another with the administration of analogues in higher long-acting doses (depot). There are controversies in the data as far as the number of ampoules to be used in the cycles with the depot GnRHa treatment, as well as regarding the number of follicles made available, the number of oocytes, fertilization, implantation and pregnancy rates. The objective of this study is to compare the use of a single long-acting depot dose to that of daily GnRHa doses in in vitro fertilization cycles. Relevant RCTs were identified by electronic search of the following databases: MEDLINE, EMBASE, LILACS (Latin American and Caribbean Center on Health Sciences Information) and the Cochrane Controlled Trials Register. Types of studies: The study analyses RCTs comparing depot and daily administration of GnRHa for long protocols in IVF treatment cycles. Couples with any cause of infertility. Types of interventions: Ovarian stimulation with human follicle stimulating hormone (hFSH) and/or human menopausal gonadotropin (hMG) and/or recombinant follicle stimulating hormone (rFSH) in IVF treatment cycles. Types of outcome measures: Clinical pregnancy rates per woman, per oocyte retrieval procedure, per embryo transfer, number of oocytes retrieved, oocyte fertilization rates, ongoing/delivered pregnancy rates per cycle started, abortion rates, multiple pregnancy rates, number of ampoules of gonadotropin employed, ovarian hyperstimulation syndrome (OHSS) incidence rates, cost analysis and patient convenience. The reviewers evaluated allocation concealment, classified as adequate, uncertain or inadequate. Two reviewers extracted the data independently. All analyses were performed according to the intention-to-treat method. Six studies, with a total of 552 women, were included and analysed. The studies do not indicate that there is statistically significant difference between the use of depot GnRHa or daily GnRHa in the primary outcome, clinical pregnancy rates per woman (OR 0.94, 95% CI 0.65 to 1.37). However, there was sufficient evidence that the use of depot GnRHa for pituitary desensitization in IVF cycles increased the number of gonadotrophins ampoules (WMD 3.30, 95% CI 1.27 to 5.34) and the duration of the ovarian stimulation (WMD 0.56, 95% CI 0.31 to 0.81), as compared with daily GnRHa. Although we recognise that the clinical pregnancy rates per woman are not the ideal primary outcome, we found no evidence of differences between the long protocol using depot or daily GnRHa for IVF cycles. However, the use of depot GnRHa is associated with increased requirements for gonadotrophins and a longer time required for ovarian stimulation. If these differences could be shown to translate into economic benefit, depot GnRHa should increase the overall costs of IVF treatment.

Immunization against GnRH in Mature Mares: Antibody Titres, Ovarian Function, Hormonal Levels and Oestrous Behaviour

The aim of the present study was to investigate the effect of active immunization against GnRH in mature Standardbred mares (three experimental and one control mare) on antibody titres, ovarian function, hormonal levels and oestrous behaviour. The mares were individually teased with a stallion once each day. During the first part of the experiment (period I: late April until November), blood was sampled every third day during the first 3 months, thereafter once per week. In the second part of the experiment (period II: December until August), sampling was carried out every second week. Progesterone, oestradiol-17beta and LH were analysed. Rectal gynaecological examination was made with the same intervals as the blood samplings and included palpation of the genital organs and ultrasonography. The experimental mares were immunized against GnRH with a GnRH-BSA conjugate. Equimune (Vetrepharm, Bracetown, Business Park, Clonee, Co. Meath, Republic of Ireland) was used as adjuvant. The mares were immunized on four occasions (20-30 day intervals) and GnRH antibody titre was determined. All immunized mares produced antibodies against GnRH but the maximum titres as well as the duration of a greater than 10% binding capacity varied between the mares (1 : 1600 to 1 : 50 000; 5 to 12 months, respectively). After the first injection, all mares showed one oestrus and ovulated at the regular time. In two of the mares, the immunization resulted in ovarian atrophy. Their hormone levels of progesterone, oestradiol- 17beta and progesterone decreased to basal levels and the cyclical hormone pattern was interrupted from approximately 30 days onwards. They continued to show oestrous signs but with irregular durations and intervals. The third mare showed ovarian suppression only for short periods and not in both ovaries at the same time; the hormone levels were basal for only about 20 days (days 50-70) and the mare ovulated on day 75 after start of immunization. The other mares ovulated after 13.5 and 15 months, respectively. It is concluded that the effect of immunization against GnRH in mature mares was individual concerning antibody titre response and the suppression of ovarian activity and hormone levels. Mares with totally inactive ovaries continued to show oestrous signs but with irregular intervals and durations.

Residual ovarian activity during oral steroid contraception.

Steroid drugs with contraceptive properties have been available in the clinical setting for over four decades and are still subject to improvement. Estrogens, progestins and anti-progestins have been used alone or in various combinations, regimens and routes of administration to favour the balance between efficacy and undesirable effects. One of the most important changes in this respect is the gradual lowering of steroid dosage in commercially available contraceptives. Current steroid contraceptive pills still achieve the goal of suppression of pituitary-ovarian activity, but the margins for error are minimal. In this review the available data on modes of action and the effects on suppressing pituitary-ovarian activity by different forms of oral contraception are reassessed. Although pregnancy rates provide a crude measure of contraceptive efficacy, no benchmark for pituitary-ovarian inhibition is available to test the suppressive potential of contraceptive drugs. Consequently, many studies provide incomplete and/or incomparable results. For the further study of those forms of steroid contraception that rely predominantly on suppression of ovarian activity, prevention of dominant follicles selection should be the objective.

Altered peripheral vascular response of women with and without pelvic pain due to congestion.

To test the hypothesis that women with pelvic venous congestion have a reduction of reactivity of their peripheral circulation. Comparison was made between 20 women with chronic pelvic pain due to congestion and a control group of 15 pain-free women matched for age, parity and body weight. A comparison of these results was made with those from six postmenopausal women taking hormone replacement therapy. Study and control groups were investigated during the mid-follicular phase of the menstrual cycle (days 5-9) and the mid-luteal phase (days 19-23). The study group was also investigated during the fifth month of treatment with suppression of ovarian activity with leuprorelin or medroxyprogesterone acetate or six months after hysterectomy and bilateral salpingo-oophorectomy. Head-up tilt sufficient to increase intra-vascular pressure in the toe by a standard 40 mmHg was used as a means of raising venous pressure in the lower limb. Skin capillary red blood cell velocity (flux) was measured using a laser Doppler flow probe placed over the pulp of the big toe. Heart rate and blood pressure were also recorded. The change in skin blood flow following head-up tilt was expressed as a percentage of baseline flow in the supine position. Percentage change in skin red blood cell flux, heart rate and blood pressure in response to 40 degrees head-up tilt. In the control group the median response to head-up tilt in the follicular phase was one of a reduction in flux, whereas in the luteal phase it was more variable ranging from an increase to a decrease in flux. The responses in the pelvic congestion group in both the follicular and luteal phases were similar to those of the control group in the luteal phase. A small but significant increase in heart rate in response to tilt in the pelvic pain group, compared with the control group, was interpreted as being due to a fall in venous return. Treatment of the pelvic congestion group by medical suppression of ovarian activity or total hysterectomy with bilateral salpingo-oophorectomy resulted in a significant change in response to head-up tilt from the variable type of luteal response to one of a more constant reduction in flux, similar to that of the control group in the follicular phase. A reduction in flux was also found consistently in postmenopausal women. The study confirms the hypothesis that women with pelvic pain due to congestion show a change in peripheral vascular reactivity which returns to normal after suppression of ovarian activity. It seems likely that some alteration of normal ovarian function is responsible for the observed changes in peripheral blood flow in response to a rise in venous pressure in women with pelvic congestion.

Worker policing limits the number of reproductives in a ponerine ant

Reproductive division of labour is an essential feature of insect sociality, but the regulation of sterility among colony members remains incompletely understood. Ant workers and queens are morphologically divergent and workers are only capable of producing males in a colony, although they usually do not do so. Worker policing is one mechanism proposed for their infertility and it can be expressed as either aggressive inhibition of ovarian activity among workers or destruction of worker–laid eggs. A few studies have shown that workers with developed ovaries are preferentially attacked by nest–mates, but adequate demonstration of worker policing also requires evidence that these attacks result in the suppression of ovarian activity or death. We investigated worker policing in the ponerine ant Harpegnathos saltator in which workers are able to mate and replace the founding queen. Five colonies were each divided into two groups, one of which consisted exclusively of infertile workers. Some individuals in the orphaned groups began laying eggs during the three–week separation and upon reunification these were vigorously attacked by infertile workers of the other groups. The ovarian activity of these new egg layers became inhibited, as revealed by subsequent dissection of marked individuals. Worker policing in H. saltator appears to function primarily in preventing an excess of reproductive workers.

Suppression of ovarian activity in the gilt and reversal by exogenous gonadotrophin administration.

The aim of the current experiment was to study the regulation of follicle development in the pig using a potent GnRH agonist (GnRH-A) to initially suppress follicle development. Large-White hybrid gilts (n = 8) were treated during the luteal phase with GnRH-A. Four of these GnRH-A treated gilts and four control gilts were given a GnRH bolus on days 14 and 28 after GnRH-A administration or during the luteal phase in control gilts. Blood samples were collected for 10 h for FSH and LH, after which 1500 IU PMSG were administered and the ovaries and uteri recovered 72 h later. A further four GnRH-A treated gilts and four control gilts were slaughtered either 28 days after GnRH-A administration or during the luteal phase respectively, and all follicles > or = 1 mm diameter were dissected. The mean basal plasma FSH level was lower (P < 0.01) in GnRH-A treated than control gilts and showed no response to the GnRH challenge although levels increased (P < 0.01) in control gilts. The mean basal plasma LH levels were similar (P > 0.1) in GnRH-A treated and control gilts. Whilst in GnRH-A treated gilts plasma LH levels showed no response to the GnRH challenge, plasma LH levels were increased (P < 0.01) in control gilts. Pulsatile LH secretion was abolished in GnRH-A treated but not in control gilts. Plasma oestradiol levels were lower (P < 0.001) in GnRH-A treated gilts than in control gilts, but nevertheless both GnRH-A treated and control gilts responded to PMSG with increased plasma oestradiol levels. Treatment with GnRH-A reduced both the mean (2.1 vs. 2.7 mm; P < 0.01) and the maximal follicle diameter (4 vs. 6 mm) and reduced (P < 0.01) the total number of follicles > or = 2 mm diameter compared with control gilts. Administration of PMSG increased both mean follicle diameter (5.1 vs. 4.4 mm; P < 0.01) and maximal follicle diameter (7 vs. 9 mm) and caused a reduction (P < 0.001) in the total number of follicles > or = 2 mm diameter in both GnRH-A treated and control gilts. In summary, this study has demonstrated, for the first time in the pig, that the inhibition of follicle development as a result of pituitary down regulation/desensitisation can be reversed by exogenous gonadotrophin treatment. This model will be a powerful tool with which to investigate the precise regulation of follicle development in the pig.

A comparative randomized trial on the impact of two low-dose oral contraceptives on ovarian activity, cervical permeability, and endometrial receptivity

In a double-blind randomized study, the suppression of ovarian activity and anti-conceptive effects on the cervix and endometrium were assessed during administration of two low-dose monophasic oral contraceptives (20 μg ethinyl estradiol [EE], 500 μg norethisterone—Eve 20 ® [Grünenthal, Aachen, Germany]; 20 μg EE, 150 μg desogestrel—Lovelle ® [Organon, Munich, Germany]). One hundred eighteen healthy women (ages: 18–35 years) were studied in 10 investigation centers during medication with either Eve 20 (n = 59) or Lovelle (n = 59). During three treatment cycles, ovarian activity was evaluated by somographic determination of follicle-like structures (FLS) and by simultaneous assessment of serum endocrine profiles (gonadotropins LH and FSH, ovarian steroids estradiol [E 2] and progesterone [P]). While on either treatment, no ovarian activity (as judged by no FLS and/or reduced sex steroid levels) was found in 90.8% (Eve 20) and 97.2% (Lovelle) of all investigated cycles. Follicular activity or cyst formation were detected in 18 of 173 cycles (Eve 20) and in 5 of 175 cycles (Lovelle), respectively. Gonadotropin levels were suppressed (LH < 6 IU/L, FSH < 8 IU/L) in most treatment cycles (Eve 20 76.6% vs. Lovelle: 84.8%). Serum E 2 concentrations exceeding 0.1 nmol/L indicated residual follicular activity in 19.3% (Eve 20) versus 12.2% (Lovelle) of all cycles. As estimated by serum P levels over 5 nmol/L, ovulation had presumably occurred in 4.1% (Eve 20) versus 2.9% (Lovelle) of treatment cycles. However, when the sonographical and endocrinological data were combined, no ovulation was documented in any pill cycle. The quality and quantity of the cervical mucus was found to be minimal in the majority of women. Moreover, the endometrial layer was determined to be low by ultrasound during most pill cycles, indicating equally strong suppressive effects on endometrial receptivity by the two contraceptives. These observations suggest that ovarian activity is suppressed in the majority of cycles during use of low-dose contraceptives. This effect may mainly be mediated by pronounced suppression of serum gonadotropin levels. Strong anti-conceptive effects of these formulations on both cervical permeability and endometrial receptivity are additional factors ensuring the contraceptive efficacy of these formulations.

The effects of monophasic and triphasic oral contraceptives on ovarian function and endometrial thickness

Objective To analyze and compare the effects of seven low-dose oral contraceptives (OCs) on ovarian function and endometrial thickness.Methods Cross-sectional study of users of one of five monophasic OCs, one of two triphasic OCs and a control group of non-users. Ovarian function, endometrial thickness and serum hormone levels were monitored during days 10–12 and 16–18 of the cycle.Results Serum estradiol was suppressed in OC users to a greater degree during days 16–18 than during days 10–12, whereas serum progesterone during days 16–18 was in the anovulatory range with each preparation. Ovarian activity as measured by follicular size was lowest with desogestrel-containing OCs, whereas greater activity was seen with triphasic levonorgestrel/ ethinylestradiol and triphasic norgestimate/ethinylestradiol. Endometrial thickness in OC users was significantly smaller than in controls.Conclusions All preparations demonstrated profound suppression of ovarian activity and effectively prevented ovulation. Ovarian suppression with desogestrel/ethinylestradiol 150/ 20 did not differ from that of other OCs despite its lower ethinylestradiol content. The use of both triphasic OCs, having a relatively low progestogenic activity, was associated with a higher ovarian activity than that of the monophasic OCs.

ADJUVANT CHEMOENDOCRINE THERAPY FOR EARLY BREAST-CANCER - IS IT WORTHWHILE - (REVIEW)

The overview published in 1999 by the Early Breast Cancer Trialist' Cooperative Group demonstrated that systemic therapy after surgical removal of primary breast tumors prolongs both disease-free and overall survival of patients when compared with no systemic therapy, Specifically, both chemotherapy and ovarian ablation in patients aged less than 50 and tamoxifen in those aged 50 or more achieve a reduction of one-fifth to one-fourth in the annual odds of recurrence or death from any cause. The relative effect of different therapies is independent of the stage of the disease, while the absolute benefit depends not only upon the relative effect of treatment but also upon the baseline prognosis of patients. The overview did not report a direct estimation of the effect of combined chemoendocrine adjuvant therapy. Among the effects that may confound the evaluation of chemoendocrine adjuvant therapy are: (a) the possibility of biological interactions between drugs; (b) the presence on tumor cells of steroid hormone receptors; (c) the suppression of ovarian activity induced by chemotherapy in most premenopausal patients; (d) the scheduling of chemotherapy and endocrine therapy. Based on data of the overview, relevant questions are: (i) does the addition of endocrine therapy (tamoxifen dr ovarian ablation) to chemotherapy improve the outcome of premenopausal patients? (ii) does the addition of chemotherapy to tamoxifen improve the outcome of postmenopausal patients? We have reviewed single randomised trials in an attempt to answer these questions. In premenopausal patients, the addition of tamoxifen to chemotherapy probably induces only small advantages. The addition of ovarian ablation to chemotherapy could improve survival. The relationship between oophorectomy and receptor status has not been extensively studied; however, the addition of oophorectomy, like the addition of tamoxifen, to chemotherapy could be cost effective in cases of estrogen receptor-positive tumors. The effect of tamoxifen in association with ovarian ablation, after chemotherapy, has not yet been studied. In postmenopausal patients the addition of chemotherapy to tamoxifen is debated. The role of receptor status seems to be important in these patients. Most studies found that chemotherapy does not significantly increase the effect of tamoxifen in the subgroup of patients with receptor-positive tumors, while it does increase toxicity. On the contrary, the addition of chemotherapy to tamoxifen, in patients with receptor-negative tumors could significantly improve results.