Heatr9 is an infection responsive gene that affects cytokine production in alveolar epithelial cells.

During infection, viruses enter susceptible host cells in order to replicate their components for production of new virions. In the process of infection, the gene expression of infected cells undergoes changes because of the production of viral components and due to the host response from detection of viral products. In the advent of RNA sequencing, the discovery of new genes and their functions in the host response generates new avenues for interventions in the host-pathogen interaction. We have identified a novel gene, Heatr9, as a virus and cytokine inducible viral responsive gene. We confirm Heatr9's expression in vitro and in vivo during virus infection and correlate it with viral burden. Heatr9 is induced by influenza virus and RSV. Heatr9 knockdown during viral infection was shown to affect chemokine expression. Our studies identify Heatr9 as a novel inflammatory and virus infection induced gene that can regulate the induction of specific cytokines.

A comparative and longitudinal study on endocrine changes related to ovarian function in patients with anorexia nervosa.

Screening of androgens and estrogens in blood and a GnRH test were performed in 20 female patients with anorexia nervosa and in 10 lean and 10 normal weight healthy control subjects. Both control groups had regular ovulatory menstrual cycles. The investigation was performed in the mid-follicular phase. Several variables showed significant differences between the groups; the levels of PRL, estrone, estradiol, progesterone, testosterone, androstenedione, and LH were lowest in the patients with anorexia nervosa. The lean control group showed intermediate values for progesterone, androstenedione, and, to a smaller extent, testosterone. The FSH response to GnRH was significantly higher in the patient group, corresponding to the pattern of late prepubertal girls. Ten patients were seen in a follow-up study. Five had resumption of the menstrual cycle, and the others still had amenorrhea. The two subgroups did not differ in either weight gain or the basal hormonal variables investigated. After weight gain an increased LH response to GnRH was observed in both subgroups. Patients who had resumption of the menstrual cycle showed a higher response of LH to GnRH, both before and after weight gain. The mean increase in LH after GnRH administration was significantly different between the two subgroups. The results suggest that the GnRH test may be useful to assess the stage of the disease and to predict the outcome, especially with regard to restoration of the menstrual cycle.

Preliminary results with the antiprogestational compound RU-486 (mifepristone) for interruption of early pregnancy.

RU-486 (mifepristone) (Roussel-Uclaf, Paris, France) is an antiprogesterone that acts through a competitive binding at the site of the progesterone and cortisol receptor. It induced a complete expulsion in 29 (83%) of 35 patients with an unwanted pregnancy with up to 55 days of amenorrhea. A complete expulsion occurred in 17 (89%) of the 19 nulliparous women, and no serious side effects were seen. However, our results were less successful in ine patients with a more advanced pregnancy (between 8 and 10 weeks). In this group, only three complete expulsions were seen.

A comparison of high-dose estrogens versus low-dose ethinylestradiol and norgestrel combination in postcoital interception: a study in 493 women.

Ethinylestradiol (EE), at a dosage of 5 mg/day for 5 consecutive days (5 mg EE), has generally been used for interception. A combination of 200 micrograms EE and 2 mg dl-norgestrel (EE + NG) was proposed as an effective alternative. Efficacy and tolerance of these methods were compared in a randomized, double-blind study. A group of 465 women was studied with a follow-up rate of 94.3%. In the 5 mg EE group a pregnancy rate of 0.9% was observed, and in the EE + NG group a rate of 0.4% was found. These rates differ significantly from the expected rates (P less than 0.0005, in both series). Nausea was noted in 59.1% of the 5 mg EE group and in 54.0% of the EE + NG series. Nausea and vomiting occurred in 20.8% and 15.8%, respectively. The efficacy of both methods as alternative morning-after medication was confirmed. The new method is preferable because treatment is limited to only 1 day.

PIP: Ethinyl estradiol (EE), at a dosage of 5 mg/day for 5 consecutive days (5 mg EE) has generally been used for interception. A combination of 200 mcg EE and 2 mg dl--norgestrel (EE+NG) was porposed as an effective alternative. Efficacy and tolerance of these methods were compared in a randomized, double-blind study. A group of 465 women was studied with a follow-up rate of 94.3%. In the 5 mg EE group, a pregnancy rate of 0.9% was observed, and in the EE+NG group, a rate of 0.4% was found. These rates differ significantly from the expected rates (P0.0005, in both series). Nausea was noted in 59.1% of the 5 mg EE group in and 54.0% of the EE+NG group. Nausea and vomiting occurred in 20.8% and 15.8% respectively. The efficacy of both methods as alternative to morning-after medication was confirmed. The new method is preferable since treatment is limited to only 1 day.

Endocrinological and clinical investigations in post-menopausal women following administration of vaginal cream containing oestriol.

The maturation value (MV), cervical mucus parameters (ferning, Spinnbarkeit), oestrone (E1), oestradiol (E2), oestriol (E3), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), thyrotropin (TSH), growth hormone (GH), sex hormone binding globulin (SHBG), corticosteroid binding globulin (CBG) and thyroxin-binding globulin (TBG) were determined in 11 post-menopausal women presenting with vaginal atrophy prior to, and following, treatment with Ovestin vaginal cream containing 0.5 mg/day of E3 for 8 wk. In 6 of the patients E3 was measured during frequent plasma sampling on days 1, 21 and 56; in the same patients and on the same days TRH-stimulated PRL, TSH and GH levels were estimated. While the therapy induced a sharp rise in the MV, there was a moderate effect on ferning/Spinnbarkeit. Baseline E3 rose from undetectable levels to a mean value of 86.8 pmol/l at day 21. E3 levels achieved during frequent plasma sampling were higher on day 1 than on days 21 and 56 - a decline of the areas under the response curves being significant (P2-sided = 0.03). There was a slight suppression of FSH and LH. No changes in the circulating levels of E1, E2, SHBG, CBG, TBG, PRL, TSH and GH were seen. TRH-stimulated PRL, TSH and GH levels remained unaffected. Clinical effect was excellent and no untoward effects were reported.

Disturbance of tryptophan metabolism and its correction during oestrogen treatment in postmenopausal women.

A relative pyridoxine deficiency was found in all of 12 women using conjugated oestrogens unopposed by progestagsns. This was due to disturbed tryptophan metabolism, expressed in increased xanthurenic acid (XA) excretion (greater than or equal to 60 mumol/8 h) during 8 h following oral administration of 2 g L-tryptophan. The intake of synthetic oestrogens such as ethinyl oestradiol has already been found to lead to a disturbance of tryptophan metabolism and to a deficiency of vitamin B6. Now we have evidence that this is the case not only in women taking oestrogens in oral contraceptives but also as replacement therapy during the postmenopause. This disturbance is clear after 1 yr of oestrogen treatment. Xanthurenic acid excretion was only slightly increased in 3 women who used progestagens in high dosages at the same time. The biochemical changes induced could easily be corrected by administration of vitamin B6. Our cyclic treatment regimen now consists of 25 days of oestrogens per month. In the remaining days a 250 mg tablet per day of vitamin B6 is prescribed.

Progesterone receptors in human oestrogen target tissues.

The levels of specific oestrogen and progesterone receptors have been measured in myometrial, endometrial and vaginal tissues obtained from 18 women between the ages of 28-73 yr. High speed cytosols of the three tissues were incubated at four different concentrations of specific ligands: E2 for the oestrogen receptor (ERc) and Org-2058 for the progesterone receptor (PgRc). Separation of bound and free hormones was done by dextran-coated charcoal; data were analysed according to Scatchard. In the myometrium and endometrium both PgRc and ERc were found. In the vaginal tissues obtained from the same patients only ERc was present. There was no evidence of specific progesterone receptors in the vagina. Both clinical and histological findings indicate that the vagina is an oestrogen-sensitive organ. Therefore, it is surprising that progesterone receptors, which are considered to be a specific response of oestrogen target tissue, are absent in the human vagina. This finding suggests that the induction of the progesterone receptors is not a specific response to oestrogen stimulation in the human vagina.

The treatment of postmenopausal vaginal atrophy with Ovestin vaginal cream or suppositories: clinical, endocrinological and safety aspects.

Seventy-four postmenopausal women presenting with vaginal atrophy were treated with either Ovestin vaginal cream (Group A, 23 women: 1 mg/day E3; Group B, 30 women: 0.5 mg/day E3) or vaginal suppositories (Group C, 21 women: 0.5 mg/day E3), applied daily for 3 wk (A and B) or 2 wk (C) before retiring. Ten women from A and 10 from B applied a maintenance dose (1 application twice weekly) during wk 4-16. Effects on vaginal cytology, cervical mucus and clinical and colposcopic findings were studied. Endometrial biopsies were done in 16 patients (A) before and after 3 wk of treatment, and, in 8 of the cases, at 16 wk. A routine laboratory screening program was performed before and after 16 wk of treatment in 10 patients (A). Plasma samples for hormone level determinations were obtained in 32 patients. Clinical and colposcopic findings showed a beneficial effect of treatments, confirmed by vaginal smears, and persisting during maintenance therapy. Effect on cervical mucus was slight to moderate. No side effects occurred and tolerance was very good. Endometrium remained atrophic under treatment. Screening program revealed no abnormalities. Treatments induced a sharp rise in plasma E3, followed by a gradual decline. Gonadotropins were slightly suppressed. E1, E2, PRL and SHBG capacity remained unchanged.

Endometrial response in estrogen replacement therapy quarterly combined with a progestogen.

OBJECTIVE: The aim of the study was to investigate the endometrial histology and the bleeding pattern under a hormone replacement therapy regimen with continuous estrogen quarterly (3-monthly) combined with a progestogen. METHODS: In a prospective, double-blind, randomised clinical trial, 30 healthy, postmenopausal women were allocated to one of the three trial preparations. Group I was treated with 1 mg micronized 17 beta-estradiol continuously, group II took 2 mg micronized 17 beta-estradiol continuously and group III took 1 mg and 2 mg 17 beta-estradiol alternating every 42 days (step-up regimen). One treatment cycle was 84 days, during the last 12 days estradiol was combined with 50 micrograms gestodene. The total treatment period comprised two cycles of 12 weeks each. With regard to endometrial histology, the second cycle was the actual study cycle. In each patient endometrial samples were obtained at the following time points: after the withdrawal bleeding in the beginning (day 8-11) of cycle II (Vabra-method), at the end of the estrogen mono-phase (day 70-72) of cycle II(Pipelle-method), and 8-11 days after cessation of all medication (Vabra-method). Histopathological classification was done by two experienced gynaecological pathologists. All patients kept record of their bleeding events in a diary. Analysis of variance and Kruskal-Wallis test were used for statistical analysis of the data. RESULTS: 29 patients were evaluable for the assessment of endometrial histology. Only one sampling procedure (1.2%) yielded an insufficient amount of tissue. In each treatment group, simple (cystic) hyperplasia was observed exclusively at the end of the estrogen mono-phase (in total 4/29 patients, 14.8%). Hyperplasia disappeared in all cases after the combined estrogen-progestogen phase. No cytological atypia was seen. Fifty-five cycles were evaluable for the bleeding pattern. The onset of the scheduled bleeding (withdrawal bleeding) was in all cycles on day 11 of the combined phase or beyond. Unlike the duration, the severity of the scheduled bleeding episodes was estrogen-dose dependent. In the entire treatment period of 2 x 84 days, breakthrough bleeding occurred in 3 women, totalling 9 days. Spotting occurred rarely and was equally divided among the treatment groups. CONCLUSIONS: A quarterly sequential hormone replacement therapy regimen for women with anintact uterus gives rise to the development of simple hyperplasia without cytological atypia at the end of the unopposed estrogen phase. This occurs independent of the estrogen dose and can be reverted to inactive or atrophic endometrium by the addition of gestodene during 12 days. The combination offers good cycle control. The safety aspects should be investigated further in long-term studies before this regimen can be advocated for routine use.

Emergency contraception: a review.

In the Netherlands, many women use a postcoital method of contraception in "emergency" situations. Postcoital contraception started in the 1960's with the administration of large doses of estrogens: 50 mg diethylstilbestrol for 5 days or 5 mg ethinylestradiol for 5 days. In the eighties, a double-blind study compared the original hormonal therapy of 5 mg ethinylestradiol for 5 days with a combination pill containing just 0.1 mg in combination with 1 mg d1-norgestrel, of which two doses are give, the second 12 hours after the first. This method was as effective in preventing pregnancy as the original treatment with high estrogen dosage. Moreover, it resulted in women suffering less nausea and vomiting. One study from Hong Kong indicated that levonorgestrel without ethinylestradiol was as effective as the combination. Postcoital use of an intrauterine device to prevent pregnancy can be used as an alternative to the hormonal method. A recent development is the use of an antiprogestagen pill: 600 mg Mifepristone on day 27 of the cycle; side effects are minimal and the success rate is high. Mifepristone should be registered and made available in all countries for this indication.

PIP: Many women in the Netherlands depend on a postcoital contraceptive (PCC) method in situations of unprotected intercourse. The incidence rate for abortions and for adolescent pregnancies in the Netherlands is the lowest worldwide. Dutch society matter-of-factly accepts adolescent sexuality and provides formal and informal sex education and readily accessible contraceptive services. Emergency contraception should be administered within 72 hours after unprotected intercourse (e.g., rape or incest) or mechanical contraceptive failure. Administration of 5 mg ethinyl estradiol (EE) for 5 days as a PCC first occurred in the Netherlands in 1964, and PCC usage peaked at 55,000 in 1975. Side effects of EE include, in order of frequency, nausea, vomiting, tender breasts, and menorrhagia. Possible modes of action for EE are more rapid transport of fertilized ova through the oviduct and slowed maturation of the endometrium, resulting in suppressed implantation. The Yuzpe PCC method involves 4 tablets of a combined oral contraceptive (each tablet with 50 mcg EE + 250 mcg levonorgestrel) administered within 72 hours followed by 2 tablets 12 hours later. Side effects are similar to those of EE alone, as is the effectiveness rate. A dose of 0.75 mg levonorgestrel alone is as effective at preventing pregnancy as the Yuzpe regimen. Side effects are considerably less common with the levonorgestrel regimen than the Yuzpe regimen. For women who present more than 72 hours after and less than 7 days after unprotected intercourse or for those with contraindications to estrogen, a copper-releasing IUD can serve as a PCC. A postcoital IUD can cause serious complications for women with a sexually transmitted disease, however. Taking RU-486 during the luteal phase of the menstrual cycle greatly drops plasma levels of progesterone and estradiol. Postovulatory administration of an antiprogestogen is the best PCC method because of minimal side effects and a high success rate.

Late second trimester abortion with 16,16-dimethyl-trans-delta 2-PGE1 methyl ester (gemeprost).

The use of gemeprost (16,16-dimethyl-trans-delta 2-PGE1 methyl ester) vaginal pessaries for the termination of pregnancy in the late second trimester has been investigated in an open single-center study. Of 56 nulliparous women between 18 and 22 weeks amenorrhoea, 33 (58.9%) aborted after the administration of 1 mg gemeprost pessaries; 5 women did abort after 3 doses, 10 after 4 doses and 18 after 5 doses. There was no statistical correlation between gestational age and abortion. The mean induction-abortion interval was 15.2 hrs (range 8.5-20.3 hrs). There were no serious complications. The safe induction of therapeutic abortion in 58.9% of women using vaginal gemeprost pessaries alone offers an acceptable alternative to surgical evacuation in the late second trimester but should not be started without the possibility to terminate the procedure by dilatation and evacuation (D + E).

The incidence of gonorrhea in an abortion population.

The incidence of gonorrhea was investigated in an abortion population. A total of 1021 women participated in this study. Three asymptomatic cases of gonorrhea were detected. None of these women had had gonorrhea before or had a previous abortion. No relation was found between the incidence of gonorrhea and age. The abortion population in our community cannot be considered to be a high-risk group for gonorrhea. In our opinion, this low incidence neither justifies routine gonococcal culture nor the prophylactic use of antibiotics in the abortion population.

PIP: An abortion population of 1021 women at a clinic in the Netherlands was investigated as to the incidence of gonorrhea among them. The sampling of women was believed to be representative in age, nationality, and marital status of the total abortion population at the clinic. There was no significant connection between previous abortion and venereal disease. Gonorrhea was proven in only 3 out of these 1021 women. A positive cervical culture offered the proof; the urethral cultures were negative. All the 3 cases were asymptomatic. None of the 3 women had had gonorrhea previously nor had they had a previous abortion. The incidence of gonorrhea was not associated with age. This low incidence of gonorrhea among the abortion population does not justify routine gonococcal culture or prophylactic use of antibiotics in the abortion procedure.

In vivo measurements of uterine cavities in 795 women of fertile age.

The uterine sound length, the functional length of the cervix including the zone of internal cervical os and the fundus transversal were determined in 795 fertile women in vivo using a measuring device, the Cavimeter. The functional cavity length was calculated by subtracting the functional length of the cervix from the uterine sound length. With growing parity, the uterine length and width increase, but with advance in age, the uterine cavity changes are not so distinct. The wide ranges found by the investigation demonstrate the individuality of the uterine cavity and the desire to measure it prior to fitting an IUD. The use of adapted IUDs according to the size of the uterine cavity leads to a remarkable reduction of side effects, particularly expulsion, bleeding and cramps caused mainly by dimensional incompatibility. Therefore prefit uterine cavity measurement can lead to better efficacy of IUDs, increased rates of acceptance and higher continuation rates.

PIP: The uterine sound length, the functional length of the cervix including the zone of internal cervical os, and the fundus transversal were determined in 795 fertile women in vivo using a measuring device called the Cavimeter. The functional cavity length was calculated by subtracting the functional length of the cervix from the uterine sound length. With growing parity, the uterine length and width increase, but with advancing age, the uterine cavity changes are not so distinct. The wide ranges found by the investigation demonstrate the individuality of the uterine cavity and the desire to measure it prior to fitting an IUD. The use of adapted IUDs according to the size of the uterine cavity leeads to a remarkable reduction in side effects, particularly expulsion, bleeding, and cramps caused mainly by dimensional incompatibility. Therefore, prefit uterine cavity measurement can lead to better efficacy of IUDs, increased rates of acceptance, and higher continuation rates.

IUD insertion following induced abortion.

In a multicenter survey, women who received an IUD immediately after abortion were compared with abortion patients who started using oral contraception. Additionally, women receiving a Nova T were compared with women receiving a Multiload 250. Follow-up data were gathered after 6 weeks. Pain was a common phenomenon post-abortum. In the study group of IUD users, complaints about pain were not more frequent than among controls, but if pain was experienced, it was more intense and of longer duration among IUD users. Bleeding immediately following the induced abortion was less frequent among IUD users, but if bleeding occurred, it tended to last longer. The first menstrual period after the induced abortion was heavier and more painful among IUD users. Expulsion of the IUD occurred in 10 cases (3.3%), all of them with the Nova T, none with Multiload. The study did not generate evidence for an increased risk of PID in women receiving an IUD after an induced abortion.

Interception II: postcoital low-dose estrogens and norgestrel combination in 633 women.

The new low-dose hormonal postcoital method, a combination of 200 mcg ethinylestradiol and 2 mg norgestrel was used in 633 women, and a statistically significantly lower observed pregnancy rate was found compared to the expected number of pregnancies if no contraception was used. Patterns of menstruation, its onset and duration, after use of this morning-after pill, are documented in respect to follicular, midcycle and luteal administration. Individual side effects such as nausea, vomiting and mastalgia are noted, but antiemetics did not reduce the incidence. Though efficacy of this technique is not found to be favorable in comparison to the 5 mg ethinylestradiol treatment, the low-dose of steroid, the one-day treatment and its lesser side effects show this alternative morning-after pill suitable for use as a first choice in case of an unprotected sexual encounter.

Termination of second trimester pregnancy with intraamniotic administration of 16-phenoxy-omega-tetranor-PgE2-methylsulfonamide (SHB 286) alone and combined with oxytocin and calcium gluconate.

Midtrimester abortion was succesfully induced within 30 hours in 62 out of 90 patients by intraamniotic administration of 16-phenoxy-omega-17,18,19, 20-tetranor-prostaglandine-E2-methylsulfonamide. The Pg-analogue was tested in 5 groups of patients which received 1,2 or 3 mg. In group IV, 2 mg of the analogue was combined with oxytocin. In group V, 3 mg of the analogue was combined with 2.75 grams of calcium gluconate. The success rate was significantly influenced by the amount of the drug administered. Side effects were minimal. Multiparous women respond better to the therapy than nulliparous patients. The combination with oxytocin was more effective than the Pg-analogue alone and the combination of sulprostone with calcium gluconate was 87% succesful within 30 hours and 100% succesful within 36 hours.

PIP: A prostaglandin analog, 16-phenoxy-delta-17,18,19,20-tetranor-prostaglandin-E2-methylsulfonamide, was tested in 5 groups of patients which received 1, 2, or 3 mg of the analog intraamniotically. 29/46 (Groups 1-3) patients receiving only the analog expelled the fetus within 30 hours. In Group 4, 2 mg of the analog was combined with oxytocin. 22/28 expelled the fetus within 30 hours. In Group 5, 15 nulliparous and 1 multiparous woman received 3 mg of the analog together with calcium gluconate, injected intraamniotically. Although the mean induction-abortion time was not significantly influenced, the success rate was higher: 87% aborted within 30 hours and 100% within 36 hours. Clinically, the contractions in this group (5) started earlier and were stronger than in other groups. In all groups, side effects were minimal. Multiparous women responded better to therapy than nulliparous patients. Since the amount of drug influenced both the success rate and the induction-abortion interval considerably and the side effects were few, a new study using 4-mg doses is in progress.

Interception. III: Postcoital luteal contragestion by an antiprogestin (mifepristone, RU 486) in 62 women.

The new antiprogestin mifepristone (RU 486) was studied as an emergency postcoital contragestive. An actual pregnancy rate of 1.6% was observed and was related to the actual conception rate. The follow-up rate was 100%. The patterns of onset and duration of the induced menstruation after mifepristone treatment are described. This method provides a good new interceptive technique when the time for use of postcoital steroids or for a postcoital IUD insertion has lapsed.

Interception. IV: Failure of mifepristone (RU 486) as a monthly contragestive, "Lunarette".

The new antiprogestin mifepristone (RU 486) was studied as a contragestive for continuous fertility control in 24 menstrual cycles. Two pregnancies out of three conceptions continued in spite of antiprogestin treatment. To date, mifepristone at the doses used appears to be inadequate for monthly use.

Effects of seven low-dose combined oral contraceptives on sex hormone binding globulin, corticosteroid binding globulin, total and free testosterone.

The effect of seven low-dose oral contraceptive preparations on sex hormone binding globulin (SHBG), cortisol binding globulin (CBG), total and absolute free testosterone were investigated in groups of 10 healthy volunteers. All preparations contained about the same amount of ethinylestradiol but they differed in type and/or dose of progestagen. The progestagens studied were: levonorgestrel (LNG; in mono- and triphasic preparations), norethisterone (NET; in monophasic preparation), desogestrel (DSG; in mono- and biphasic preparations) and gestodene (GSD; in triphasic preparation), all 19-nortestosterone derivatives, and the anti-androgen cyproterone acetate (CPA) in a monophasic preparation. Differences observed in SHBG level, which reflect the estrogen-androgen balance, can be attributed to the intrinsic androgenic (or anti-androgenic) properties of the progestagens, and were in agreement with the results of published receptor binding studies, performed in vitro. Based on our results the following ranking (high to low) can be made with respect to the androgenicity of the preparations: monophasic LNG greater than or equal to monophasic NET = triphasic LNG greater than or equal to triphasic GSD = biphasic DSG = monophasic DSG greater than monophasic CPA. An anti-estrogenic effect of the 19-nortestosterone derived progestagens can be excluded by the effect on CBG, a marker for estrogenic activity. All preparations containing a 19-nortestosterone derived progestagen, independent of their type and dose, induce a similar rise in CBG, whereas the preparation with cyproterone acetate induced an even higher CBG level. Irrespective of the effect on total testosterone, which varies between the preparations, the absolute free testosterone level decreased to a comparable degree for all preparations.(ABSTRACT TRUNCATED AT 250 WORDS)

Interfering with implantation by postcoital estrogen administration. II. Endometrium epithelial cell ultrastructure.

Secretory human endometrium was studied by electron microscopy after high-dose ethinylestradiol administration, a method used for interception (morning-after pill). Medicated (experimental) cycles were compared to non-medicated (control) cycles in the same volunteers. The nucleolar channel system typically present in the nucleus of the epithelial cell in secretory phase of the human endometrium disappears completely as a result of this treatment, resulting in a nucleolar basket structure. Glycogen deposits were prominent at the basal membrane and in the apex of the cell during the experimental cycle. Giant mitochondria were observed to occur to similar extent during control and treatment cycles. This study confirms the morphological delay found in light microscopic studies, published earlier with diethylstilbestrol and with ethinylestradiol.

PIP: High-dose ethinylestradiol is used as a postcoital contraceptive. Its mechanism of action is to delay the secretory development of the endometrial epithelial cells. This study, using 4 normal volunteers, was undertaken to see the effects of high-dose ethinylestradiol on the ultrastructure of the endometrial cells and on glycogen metabolism during the luteal phase of the menstrual cycle. Ovulation was determined from plasma luteinizing hormone levels, and the subjects were given 5 mg ethinylestradiol for 5 consecutive days thereafter. The nucleolar channel system, which typically appears in the cell during the secretory phase, completely disappeared after treatment with ethinylestradiol. Moreover, the Golgi complexes were enlarged, and large amounts of glycogen accumulated at the basal membrane and in apical vacuoles of the cells. These changes show that large doses of ethinylestradiol given after ovulation interfere with the synthesis and secretion of glycogen in the endometrial epithelial cells.