Progestational Changes Research Articles

Is letrozole affecting the beneficial changes of desogestrel at the endometrial level in patients with endometriosis?

OBJECTIVE: Cell proliferation is increased and apoptosis is diminished in eutopic endometrium from patients with endometriosis (EDT), factors that may contribute to its etiopathogenesis. We previously described the reversal of those findings with the use of desogestrel (Meresman et al, 2005). In patients with EDT treated with aromatase inhibitors, a progestin is also administered in order to block the release of gonadotropins (Ailawadi et al, 2004). In the present study, we evaluated and compared the endometrial effects of treatment with desogestrel and a combination of letrozole and desogestrel on these parameters in patients with histologically proven EDT.DESIGN: Apoptosis and cell proliferation were evaluated in eutopic endometrial tissue from EDT patients.MATERIALS AND METHODS: 10 EDT patients had an endometrial biopsy before treatment, after 6 weeks of desogestrel 75 μg/day (treatment D) and then, after another 6 weeks of a combination of desogestrel 75 μg + letrozole 2.5 mg/day (treatment DL). The lesions were then fixed and stained with hematoxylin-eosin for histological analysis. Cell proliferation was assessed by PCNA immunohistochemistry before and after treatments. Determination of apoptosis was done in the same tissue by the TUNEL assay.RESULTS: PCNA index was assessed in eutopic endometrium from EDT patients before treatment and observed 36.08±4.8% positive cells. After treatment D, cell proliferation was significantly suppressed to 12.36±2.8% positive cells (p<0.01). Similarly, the treatment DL caused a significant decrease in cell proliferation to 14.71±3.9% positive cells (p<0.01). Likewise, both treatments significantly increased apoptosis in eutopic endometrium from EDT patients from 2.49±0.6% apoptotic cells (APc) before treatment to 12.98±2.1% APc after desogestrel administration (p<0.01) and to 12.2±3.7% APc after the combined treatment (p<0.01). Histologically, under treatment D the endometrial glands and the stroma showed discrepancy, with a more advanced stroma, highlighted by progestational changes and minimal proliferation, while under treatment DL both endometrial components showed advanced progestational changes and complete absence of endometrial proliferation.CONCLUSIONS: Desogestrel and the combination of letrozole and desogestrel significantly diminished cell proliferation and induced apoptosis in eutopic endometrial tissue from EDT patients. These data may have clinical relevance in the treatment of EDT. OBJECTIVE: Cell proliferation is increased and apoptosis is diminished in eutopic endometrium from patients with endometriosis (EDT), factors that may contribute to its etiopathogenesis. We previously described the reversal of those findings with the use of desogestrel (Meresman et al, 2005). In patients with EDT treated with aromatase inhibitors, a progestin is also administered in order to block the release of gonadotropins (Ailawadi et al, 2004). In the present study, we evaluated and compared the endometrial effects of treatment with desogestrel and a combination of letrozole and desogestrel on these parameters in patients with histologically proven EDT. DESIGN: Apoptosis and cell proliferation were evaluated in eutopic endometrial tissue from EDT patients. MATERIALS AND METHODS: 10 EDT patients had an endometrial biopsy before treatment, after 6 weeks of desogestrel 75 μg/day (treatment D) and then, after another 6 weeks of a combination of desogestrel 75 μg + letrozole 2.5 mg/day (treatment DL). The lesions were then fixed and stained with hematoxylin-eosin for histological analysis. Cell proliferation was assessed by PCNA immunohistochemistry before and after treatments. Determination of apoptosis was done in the same tissue by the TUNEL assay. RESULTS: PCNA index was assessed in eutopic endometrium from EDT patients before treatment and observed 36.08±4.8% positive cells. After treatment D, cell proliferation was significantly suppressed to 12.36±2.8% positive cells (p<0.01). Similarly, the treatment DL caused a significant decrease in cell proliferation to 14.71±3.9% positive cells (p<0.01). Likewise, both treatments significantly increased apoptosis in eutopic endometrium from EDT patients from 2.49±0.6% apoptotic cells (APc) before treatment to 12.98±2.1% APc after desogestrel administration (p<0.01) and to 12.2±3.7% APc after the combined treatment (p<0.01). Histologically, under treatment D the endometrial glands and the stroma showed discrepancy, with a more advanced stroma, highlighted by progestational changes and minimal proliferation, while under treatment DL both endometrial components showed advanced progestational changes and complete absence of endometrial proliferation. CONCLUSIONS: Desogestrel and the combination of letrozole and desogestrel significantly diminished cell proliferation and induced apoptosis in eutopic endometrial tissue from EDT patients. These data may have clinical relevance in the treatment of EDT.

Sexual Function in Chronic Kidney Disease

Endocrine abnormalities are common in patients with chronic kidney disease (CKD) and lead to sexual dysfunction, anemia, hyperparathyroidism, and altered mineral metabolism. Common clinical problems include disturbances in menstruation in women, erectile dysfunction in men, and decreased libido and infertility in both sexes. Organic factors tend to be prominent and are related to uremia and other comorbid illnesses. Psychological factors and depression may exacerbate the primary problem. Alterations in the hypothalamic-pituitary axis are seen early in CKD and tend to worsen after patients start dialysis. Hypogonadism plays a dominant role in male sexual function, whereas changes in hypothalamic-pituitary function predominate in female sexual dysfunction. In patients on dialysis, treatment strategies include optimizing dose of dialysis, correction of anemia with erythropoietin, and correction of hyperparathyroidism. Successful kidney transplantation may restore normal sexual function, especially in younger patients.

A new clinical option for hormone replacement therapy in women with secondary amenorrhea: Effects of cyclic administration of progesterone from the sustained-release vaginal gel Crinone (4% and 8%) on endometrial morphologic features and withdrawal bleeding

Objective: The objective of this study was to evaluate the safety and efficacy of 2 doses of a transvaginal polycarbophil-based progesterone gel (4% and 8%) in hormone replacement therapy. Study Design: This multicenter, randomized, parallel-group, open-label 3-month study included 127 women with secondary amenorrhea. Estrogenized patients applied transvaginal progesterone (4% or 8%) every other day for 6 doses per month. Efficacy was based on endometrial biopsy findings and withdrawal bleeding. McNemar's test was used to compare incidence of adverse events before and during treatment. Results: Progestational changes were found in 92% (Crinone 4%) and 100% (Crinone 8%) of patients with evaluable biopsies. Withdrawal bleeding was experienced by 81% (Crinone 4%) and 82% (Crinone 8%) of the patients. No patient experienced any serious side effect related to treatment. The incidence of most side effects, including psychologic symptoms, decreased with progesterone treatment compared with estrogen alone therapy. Compliance exceeded 98% for both doses. Conclusions: Crinone is a novel, effective, and well-tolerated option for hormone replacement therapy in women with secondary amenorrhea. (Am J Obstet Gynecol 1999;180:42-8.)

Depot leuprolide acetate with estrogen and progestin add-back for long-term treatment of premenstrual syndrome

To test the effectiveness and safety of long-term depot leuprolide acetate (GnRH-a) plus estrogen and progestin add-back therapy in the treatment of moderate and severe premenstrual syndrome (PMS).A prospective trial with each patient serving as her own control.University teaching hospital.Ten women with regular menstrual cycles complaining of moderate to severe PMS. Premenstrual syndrome was diagnosed when symptoms increased > or = 25% during the luteal phase.Four-week cycles of IM injections of placebo or GnRH-a with all patients receiving saline (placebo), the first cycle followed by 12 cycles of GnRH-a, 7.5 mg. Conjugated equine estrogen (0.625 mg/d) was started Monday through Saturday within the first cycle and increased as needed. Medroxyprogesterone acetate (MPA), 10 mg/d, was taken orally for 10 days after 4, 8, and 12 cycles of GnRH-a therapy.Changes in three symptom categories (water retention, pain, and psychological function), serum levels of total cholesterol and HDL, HDL-2, and LDL cholesterol, E2, and estrone. Endometrial biopsy was obtained 1 day after the end of the 12th GnRH-a cycle, and bone density was assessed using quantitative computer tomography at the end of the 12th GnRH-a cycle.During treatment, there was a significant decrease compared with baseline and placebo in all three symptom categories. There were no significant changes in lipids. Endometrial biopsies revealed progestational changes with no evidence of hyperplasia. Quantitative computer tomography bone density dropped 3.7 on average compared with baseline after 12 months of treatment, but this was not statistically significant.Gonadotropin-releasing hormone agonist therapy with hormonal add-back therapy is effective in treating PMS symptoms with progressive improvement over a 12-month period. This therapy prevents changes in lipids and adequately protects the endometrium with the addition of MPA every 4th cycle. Quantitative computer tomography bone density dropped at 12 months; further examination of bone changes is necessary.

Uterine Receptivity

Reduced uterine receptivity can play a major role in human infertility, particularly following ovarian stimulation as occurs during ovulation induction and IVF. Many of the conventional histological and morphological markers used to identify normal progestational changes in the human uterus are inadequate as markers of uterine receptivity for implantation, and new techniques including ultrasound and morphometric measurement will be required. At the same time, a'better understanding of the cellular processes involved in human implantation is required if we are to identify markers of uterine receptivity. Recent observations suggest that the uterus is normally a barrier to embryo implantation and that uterine receptivity is in fact the loss of this barrier function, rather than the acquisition of new structural or functional capabilities.

Endocrine regulation of the corpus luteum.

The corpus luteum is a small gland that develops rapidly from the ovulated follicle and performs a vital function in the reproductive process, namely, the secretion of progesterone, which is necessary for implantation of the blasto­ cyst. Following implantation, the continued secretion of progesterone is essential to maintain a quiescent uterus and an intrauterine environment that is conducive to continued development of the embryo (29). If fertilization or implantation does not occur, the corpus luteum regresses, and the consequent withdrawal of progesterone leads to increased frequency of pulsatile luteiniz­ ing hormone (LH) secretion, increased follicular estrogen synthesis, and a new follicular phase (56). If implantation occurs, then the embryo signals the corpus luteum either directly or indirectly to continue to secrete progesterone and to prevent the corpus luteum from regressing (78). Thus, the corpus luteum can be viewed as the terminal stage of the ovarian follicle, which after shedding the oocyte, continues to nurture the (fertilized) egg indirectly by producing progesterone. The progestational changes in the uterus must pre­ cede the arrival of the preimplantation embryo and require the rapid conver­ sion of the predominantly estrogen-producing follicle to a predominantly progesterone-producing corpus luteum. This is accomplished by the pre­ ovulatory surge of luteinizing hormone, which serves the dual role of stimulating both ovulation and the conversion of the follicle into a corpus luteum, a process known as luteinization (57). This review COncentrates On certain aspects of the regulation of the corpus luteum that represent relatively new directions in research, and emerging concepts. For more information about the regulation of the corpus luteum in

Early embryonic development and preimplantation changes in the uterus of the bat Rhinopoma hardwickei hardwickei (Gray) (Rhinopomatidae).

Rhinopoma hardwickei hardwickei has an annual reproductive cycle. Although many of the females become inseminated from the latter half of February until about the middle of April, ovulation has not been recorded until the 11th of March. A single follicle reached full development and released one ovum from either of the ovaries with nearly equal frequency, and a single conceptus was carried in the ipsilateral uterine cornu during each cycle. The embryo descended into the uterus as an early morula and attained the bilaminar blastocyst stage before undergoing implantation. As the morula advanced in age, the embryonic surface of the zona became progressively more basophilic. Hence in advanced morulae, the inner surface of the zona pellucida took a dark stain with hematoxylin and appeared like a distinct thin membrane, while the rest of the thickness of the zona was eosinophilic. Although progestational changes commenced in both uterine cornua, they became augmented in the uterine cornu on the side of ovulation and blastocyst attachment. After blastocyst attachment, the contralateral cornu reverted to an anestrus condition. The progestational changes became less conspicuous from the cranial to the caudal end of the uterus. Evidently, there was a linear gradient in the progestational response of the uterus with the cranial end being most responsive and the caudal end least responsive. The precise mechanism which brings this about is not known.

Effects of antibodies to progesterone on early pregnancy in rabbits.

Effects of antibodies to progesterone on early pregnancy were studied in rabbits. A total of 124 rabbits were employed to determine the effects of active immunization with progesterone-11alpha hemisuccinate couple to bovine serum albumin (P-BSA) on progesterone-dependent responses. P-BSA was administered by multiple intradermal injections in complete Freund's adjuvant. The rabbits were bled immediately after mating to obtain an estimate of the levels of antibodies to progesterone (anti-P) and were sacrificed 1.25, 3, 5, 6, 7, or 12 days later. Immunization with P-BSA did not cause marked changes in the numbers of corpora lutea, fertilization rate or the weights of corpora lutea, adrenal glands and ovaries. Mean serum progesterone levels in rabbits immunized with P-BSA were 8-15 times higher than controls on Days 3, 5, and 7 of pregnancy. There was a highly significant positive correlation (r=.85, p less than .01) between levels of anti-P at the time of mating and serum progesterone at necropsy. The elevation in serum progesterone and the correlation with the anti-P levels were not markedly affected by replacement therapy with medroxyprogesterone acetate (MPA). In P-BSA-immunized rabbits uterine weights were significantly lower than controls (p=.05 or less than .01). Inhibition of the progestational response of the uterus in the presence of markedly elevated serum progesterone levels indicates that progesterone bound to antibody was not readily available to target organ cells. Progestational changes in the uteri of P-BSA-immunized rabbits were delayed as compared to controls. Embryo survival in the immunized rabbits was lower (p less than .01) at Days 5, 6, 7, and 12 and embryo diameters were lower (p less than .01) at Days 5, 6 and 7 of pregnancy. Embryo survival rates and diameters at Day 5, 6, and 7 were both negatively correlated (p less than .05) with the levels of anti-P at the time of mating. The detrimental effects of P-Basa immunization on progesterone-dependent responses were completely or partially blocked by MPA.

Studies on the progestational endometrium of the rabbit. I. Light microscopy, day 0 to day 13 of gonadotrophin-induced pseudopregnancy.

AbstractA study of the progestational evolution of the endometrium of the rabbit in pseudopregnancy suggests a division into the following phases: (1) priming phase (0–24 hours), in which no significant changes were observed except for leucocytic invasion of the epithelium, (2) proliferative phase (1–4 days), in which mitosis is active and the epithelium becomes pseudostratified and the glands proliferate, (3) phase of epithelial relayering and folding (4–6 days), in which the epithelium is single‐layered and there is evidence of secretory activity, (4) phase of cell fusion (6–8 days), in which the columnar cells fuse into multinucleated masses, and (5) maximally progestational phase (8–13 days), in which almost all the epithelial cells are multinucleated except for occasional ciliated cells, and, in some animals with evidence of the effects of high systemic levels of estrogen, extensive ciliation, especially antimesometrially. A final phase (6), not studied in detail, is a declining phase marked by degeneration and sloughing of the multinucleated epithelium and replacement with predominantly ciliated cells. Reconstruction of the minor mucosal folds, as distinct from the six or so major folds present in the non‐pregnant animal, shows that these are true elevations of the mucosa above the level of the mouths of the glands. The current concept of progestational changes in the endometrium of the rabbit as predominantly due to glandular proliferation is incorrect; this has important implications for analysis of the implantation process.

Progestational activity of Megestrol acetate polydimethylsiloxane (PDS) capsules in rhesus monkeys

Progestational changes took place in estrogen primed endometria of adult castrated rhesus monkeys when Megestrol acetate was given orally or when it was administered in Silastic R capsules which were introduced subcutaneously. These changes were evaluated at the end of the 10th day of treatment. Endometrial biopsies taken through uterocutaneous fistulae showed irregular secretory and irregular endometria, when 4 μg/kg/24 hrs and 8 μg/kg/24 hrs of Megestrol acetate were administered, respectively, by the implant. Endometrial suppression was obtained in equivalent degrees when 60 μg/kg/24 hrs were given orally and when 8 μg/kg/24 hrs were given by implant. Megestrol acetate was approximately 10 times more potent by implant than when administered orally. Following both routes of administration, there was an associated leukocytic infiltration of the endometrium. The progestational changes and this infiltration of the endometrium seem to be dose-related. It is suggested that the presence of lymphocytic and polymorphonuclear infiltration into the endometrium could be related to the mechanism of action of continuous microdose progestogens.

Endocrinological effects of experimentally induced extra-uterine pregnancies in virgin mice.

Summary. Experimentally induced extra-uterine pregnancies (eup) in virgin mice did not stop the oestrous cycle, inhibit mating with ensuing pregnancy or stimulate the corpora lutea sufficiently to produce progestational changes in the genital tract. The eup, however, caused changes typically associated with pregnancy in the adrenal cortex and mammary glands. In the former the X-zone either completely disappeared or underwent degenerative changes. The mammary glands showed definite lobulo-alveolar development, not affected by adrenalectomy, but abolished both by ovariectomy and hypophysectomy.

Clinical observations on a new progestational agent, "allylestrenol".

ABSTRACT 1. A new steroid, 17α-allyl-17β-hydroxy-estr-4-ene (allylestrenol) is an orally effective progestational compound. 2. Forty-three female patients received 71 courses of allylestrenol. Withdrawal bleeding occurred in 59 instances, with as low a total dosage as 50 to 75 mg over a period of five days. 3. In five of the eleven patients a thermogenic response was noted. 4. Thirty to forty milligrams of allylestrenol with 0.12 to 0.2 mg of ethinyl oestradiol-3-methyl ether successfully delayed menses when administered for 20 days starting 6 to 7 days after ovulation. 5. Allylestrenol with an oestrogen induced progestational changes in a castrated female. 6. Allylestrenol did not suppress adrenal function in 2 patients with congenital adrenal hyperplasia but did appear to have some anti-oestrogenic effects in the treatment of two children with sexual precocity. 7. Allylestrenol is a pure and safe progestational agent without apparent androgenic, oestrogenic, or other side effects.

Mediation of progestational action of amphenone by the rabbit adrenal.

SummaryProgestational proliferation of the rabbit endometrium in response to amphenone has been shown to be dependent on the adrenals. The progestational effect of amphenone was prevented by adrenalectomy as well as by cortisone treatment. Large doses of ACTH failed to produce progestational changes in the rabbit endometrium. It was suggested that amphenone exerts its progestational effect on the rabbit uterus by inhibition of specific enzyme systems in the adrenocortical biosynthetic pathway resulting in excess progestogen secretion.

Carbonic anhydrase in the female reproductive tract. II. Endometrial carbonic anhydrase as indicator of luteoid potency: correlation with progestational proliferation.

SUMMARY In an attempt to establish the measurement of uterine carbonic anhydrase activity as a quantitative test for progestationally active substances, the activity of carbonic anhydrase in the rabbit endometrium has been correlated with the conventional histological method of assaying progestational activity. The following steroids have been tested in this manner with special regard to the duration of their effect: (a) progesterone, deoxycorticosterone (DC), deoxycorticosterone acetate (DCA), 3-acetoxy-pregna-3,5-diene-20-one, 17α-hydroxy-progesterone, 17α-hydroxyprogesterone caproate (Delalutin); (b) 17α-ethinyl-19-nortestosterone, 17β-acetoxy-isoprogesterone, 3α-hydroxy-pregnane-12:20-dione, 12α-hydroxy-pregnane-3:20-dione, pregnane-3:12:20-trione, 2β-acetoxy-progesterone, 2 α-acetoxyprogesterone, pregna-5-ene-20-one. The action of DCA was weak and transient; that of progesterone and 3-acetoxy-pregna-3,5-diene-20-one was marked but of limited duration; Delalutin was powerful as well as sustained; DC and 17α-hydroxyprogesterone failed to produce true progestational changes. Ethinyl-19-nor-testosterone was the only steroid in group (b) endowed with progestational potency. Stilboestrol (2 mg) administered a day before or simultaneously with DCA (16 mg), progesterone (4 mg) or Delalutin (2 mg), suppressed the endometrial response for 5 days but did not interfere with the late (8-day) progestational effect of the long-acting progestogen Delalutin. Small doses of purified FSH induced a few ovulations in the rabbit when injected intravenously, the endometrium showed some proliferative changes by bioassay but the activity of carbonic anhydrase was not appreciably increased. Subcutaneous injections had no effect. When progesterone was administered subcutaneously with FSH its effect was curtailed. With few exceptions, there was satisfactory agreement between the enzymic and histological method of determining progestational activity.

Progestational effectiveness of 19-norethinyl-testosterone by oral route in women.

ConclusionsIt is clear from the foregoing observations that 10 mg nor-ethisterone given twice daily represents a reproducibly effective dose in women for the production of marked progestational changes in the endometrium. The data suggest that very probably one half this dose will not be effective. The comparably effective dose of ethinyl tes-tosterone (ethisterone) would be about 4 times higher(4). Thus the comparative values agree reasonably well in rabbit, monkey, and man(2,3).

OBSERVATIONS ON THE ENDOMETRIUM AND OVARY IN THE NEWBORN

Post-mortem examination of endometria of 169 newborn infants reveals that 68 per cent are in an indifferent or proliferative phase, 27 per cent show secretory activity, and 5 per cent show progestational changes including decidual transformation of the stroma and changes analogous to those seen in adult menstruation. Examination of the ovaries in 115 of these cases shows gonadotropic changes in 38 per cent. Examination of the 42 adequately sectioned ovaries from this group plus 31 from cases in which the endometrium was not available shows gonadotropic activity in 90 per cent. The observation of atretic follicles indicates that cellular response to gonadotropic stimuli is present and occasionally completed in utero. It is concluded that the endometrial and ovarian changes are unrelated and that each is secondary to a different endocrine stimulus. Evidence is adduced to indicate that progesterone is capable of traversing the "Arthus' phenomenon" thereby producing a were infective hyperplasia of the spleen, placental membrane and producing the decidual transformation of the endometrial stroma.

The conversion of desoxycorticosterone acetate to a progesterone-like substance.

IT HAS been known for some time that desoxycorticosterone acetate (DCA) possesses weak progestational activity when administered systemically. However, DCA will not bring about progestational changes when applied topically to the endometrium of the rabbit (McGinty, 1942) nor will it cause a positive reaction in the stromal nuclei of the uterus of the mouse following local application (Hooker and Forbes, 1949). Pfiffner (1942) concluded from an analysis of the structural similarities of the two molecules and from McGimVy’s data (1942) that desoxycorticosterone is converted in the body to progesterone, probably by removal of the primary hydroxyl group. Since then, evidence has been presented for the in vivo conversion of DCA to progesterone in monkeys (Zarrow, Hisaw and Bryans, 1950) but no information is available regarding the locus of this conversion. MATERIAL AND METHODS Adult rats of the Sprague-Dawley strain and grey Chinchilla rabbits were used for the studies on the site of conversion of DCA to prog...

The release of a progesterone-like substance from the adrenal gland.

The presence of progesterone in the adrenal gland has been known for some time. Engelhart, in 1930, induced progestational changes in the uteri of rabbits by treatment with a lipoidal extract of the adrenal cortex and Callow & Parkes (1936) showed the presence of progestational activity in extracts of the adrenal glands of cattle, sheep, horses and pigs. The actual isolation of progesterone from the adrenal gland was reported by Beall & Reichstein in 1938.

Direct progestational action of progesterone and certain related steroids on the endometrium of the rhesus monkey.

SUMMARY Solid intrauterine implants of certain steroids were made in prepubertal and adolescent ovariectomized and oestrone-primed rhesus monkeys. Implants of the following steroids produced localized progestational changes in the endometrial glands: progesterone, deoxycortone, ethisterone, testosterone, methyl testosterone and methyl dihydrotestosterone. Pregnenolone produced only minimal progestational effects. Pregnanediol showed no progestational effect and failed to maintain the endometrium. A comparison of the direct progestational action of a number of steroids on the endometrium has been made in the four species so far investigated (mouse, rabbit, cat and monkey, each of which represents a different mammalian order). Direct progestational action requires a fairly close structural similarity to progesterone in all cases, but the degree of similarity required shows a marked species difference.

Ovarian function following induced abortion

1.1. The ovarian function of 47 patients following a total of 48 induced abortions performed mainly for socioeconomic reasons was studied by endometrial biopsy and basal temperature methods.2.2. One hundred twenty-one endometrial biopsies were performed and 99 basal temperature records were obtained during the investigation. Sixty-seven biopsies were performed within 11 days of the menstrual onset.3.3. The ovarian function in 43 cases was studied during the postabortal cycle. 3.1.A. Twenty-six patients showed abnormal ovarian function. An anovular picture was present in half of these.3.2.B. A high incidence of abnormal function was found to be significantly related to the duration of pregnancy. While only 4 of 13 patients with gestations from 35 to 55 days showed abnormal patterns, the proportion rose to 7 of 13 in the 56 to 76 day group, and to 15 of 16 who were beyond the seventy-sixth day of gestation.3.3.C. Although no significant difference was found in the average length of the postabortal cycle as compared with the preoperative and second to seventh cycles, the degree of variation in the length of the menstrual cycles within the postabortal series was significantly greater than within the other series, indicating that the factor or factors controlling the cyclic rhythmicity of menstruation are affected in the postabortal cycle by the abrupt termination of the pregnancy.4.4. Thirty-six patients were followed after the postabortal cycle for a total of 65 menstrual cycles (second to seventh cycles). Return to normaley of ovarian function after the postabortal cycle occurred rapidly since 29 of 33 second cycles and all subsequent cycles revealed progestational changes.5.5. The mechanism of abnormal ovarian function in the postabortal cycle is not known, but may be the result of either ovarian or anterior pituitary gland insensitivity induced by abrupt and drastic removal of the placenta and the consequent withdrawal of all of its hormones.