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ObjectiveTo evaluate serum estradiol (E2) concentrations during use of 90-day contraceptive vaginal rings releasing E2 75, 100, or 200mcg/day and segesterone acetate (SA) 200mcg/day to identify a dose that avoids hypoestrogenism.Study designWe conducted a multicenter dose-finding study in healthy, reproductive-aged women with regular cycles with sequential enrollment to increasing E2 dose groups. We evaluated serum E2 concentrations twice weekly for the primary outcome of median E2 concentrations throughout initial 30-day use (target ≥40pg/mL). In an optional 2-cycle extension substudy, we randomized participants to 2- or 4-day ring-free intervals per 30-day cycle to evaluate bleeding and spotting based on daily diary information.ResultsSixty-five participants enrolled in E2 75 (n=22), 100 (n=21), and 200 (n=22)mcg/day groups; 35 participated in the substudy. Median serum E2 concentrations in 75 and 100mcg/day groups were 40pg/mL throughout 30days; E2 concentrations were 37pg/mL (range 28-62pg/mL) on days 88-90 (n=11). Among the E2 200mcg/day substudy participants, all had withdrawal bleeding following ring removal. The 2-day ring-free interval group reported zero median unscheduled bleeding and two (range 0-16) and three (range 0-19) unscheduled spotting days in extension cycles 1 and 2, respectively. The 4-day ring-free interval group reported zero median unscheduled bleeding or spotting days.ConclusionsEstradiol concentrations with rings releasing E2 200mcg/day and SA 200mcg/day avoid hypoestrogenism over 30-day use.ImplicationsA 90-day contraceptive vaginal ring releasing estradiol 200mcg/day and segesterone acetate 200mcg/day achieves estradiol concentrations that should avoid hypoestrogenism and effectively suppresses ovulation.

Objective To compare two protocols of CC therapy for induction of ovulation in a group CC resistant PCOS women. Study design Double blind randomized controlled trial. Subjects and methods 260 nulliparous CC resistant PCOS women randomized between two groups; In the first group each patient received 200 mg/day for 5 days while the second group received 100 mg/day for 10 days, both starting on day 3 of progestin induced withdrawal bleeding. Main outcome measures Ovulation defined as at least one follicle reaching ⩾14 mm diameter, and confirmed by timed serum progesterone. Secondary outcome measures included; number of dominant follicles, endometrial thickness, clinical pregnancy rate, and live birth rate. Results The extended protocol resulted in significantly higher ovulation, pregnancy, and live-birth rates than the high dose protocol ( p 0.001). Serum FSH levels on day 6 of treatment were comparable between the two groups while the level on day 11 was significantly higher in the second group ( p 0.02). Serum LH levels were comparable both on days 6 and 11. Patients on longer protocol (group II) required a longer time to ovulate (18 ± 4.4 versus 14 ± 3.6 days) but had a significantly higher endometrial thickness at the time of ovulation. ( p 0.02) FSH and LH levels were comparable between responders and non-responders in both groups. Conclusions The current study reports significantly higher ovulation and pregnancy rates with the longer lower dose protocol probably because of prolonged FSH rise. Study web address: ACTRN12611000639921.

The aim of this study was to compare the efficacy of a merocel technique with conventional nasal packing, in the classic septuplasty operation. The study is a prospective, randomized clinical trial. 60 patients underwent septuplasty for septal deviation and ensuing nasal obstruction. These patients were divided into two groups: conventional gauze packing and merocel packing. Randomization was performed using the two block randomization system. Patients who failed the regular follow-up were excluded, and the two groups were compared for postoperative bleeding, pain, hematoma, and adhesions. Patients were asked to record pain levels using a visual analogue scale. The authors found significant statistical differences between the two groups in the parameters studied, but significantly higher pain levels, Adhesions and withdrawal bleeding were noted in the patients in the gauze packing group. The final results confirmed that patients who underwent septuplasty with merocel packing had more smooth post-op recovery with less complication then conventional gauze packing.

Two 54-year-old women developed abdominal cramps and vaginal hemorrhage as a result of endometrial hyperplasia during treatment with a hop-containing phytotherapeutic product (MenoCool®) for post-menopausal complaints. The women used the hop-containing phytotherapeutic product (418 mg of hop per tablet) twice daily (1 and 0.5 tablets by both patient A and B). Patient A developed abdominal cramps and vaginal hemorrhage after 2 months of use. After gynecological examination, she was diagnosed with endometrial hyperplasia. The patient was treated with a curettage. The hop-containing phytotherapeutic product was discontinued, and the patient recovered. Patient B developed abdominal pain/cramps and vaginal hemorrhage after 5 months of use. A cervix smear, internal examination, and ultrasound were performed. Due to the thickness of the endometrium, a pipelle endometrial biopsy was performed. Results showed no indication for cervix cancer. The use of MenoCool® was ceased; follow-up information received from the patient shortly thereafter indicated that she had almost entirely recovered from the abdominal pain/cramps and vaginal hemorrhage. Hop (Humulus lupulus) has phytoestrogenic properties that may be the cause of endometrial hyperplasia and subsequent vaginal hemorrhage. A Naranjo assessment score of 5 was obtained for both cases, indicating a probable relationship between the patient’s endometrial proliferation and subsequent vaginal hemorrhage and their use of the suspect drug.

Objective: Depot GnRH agonists are commonly used in the treatment of central precocious puberty (CPP). The triptorelin 11.25 mg 3-month depot, currently used in adult indications, had not previously been evaluated in CPP. Design: This was a multicenter, open-label, 12 month trial conducted in 64 CPP children (54 girls and 10 boys), treated quarterly. Methods: Children with a clinical onset of pubertal development before the age of 8 years (girls) or 9 years (boys), pubertal response of LH to GnRH ≥7 IU/l, advanced bone age >1 year, enlarged uterus (≥36 mm) and testosterone level ≥0.5 ng/ml (boys), were included. Suppression of gonadotropic activation, as determined from serum LH, FSH, estradiol or testosterone, and pubertal signs were assessed at Months 3, 6 and 12. Results: GnRH-stimulated peak LH ≤3 IU/l, the main efficacy criterion, was met in 53 out of 62 (85%), 60 out of 62 (97%) and 56 out of 59 (95%) of the children at Months 3, 6 and 12 respectively. Serum FSH and sex steroids were also significantly reduced, while pubertal development regressed in most patients. Mean residual triptorelin levels were stable from Month 3 through to Month 12. The triptorelin 3-month depot was well tolerated. Severe injection pain was experienced in only one instance. Five girls experienced mild-to-moderate or severe (one girl) withdrawal bleeding. Conclusions: The triptorelin 3-month depot efficiently suppresses the pituitary–gonadal axis and pubertal development in children with CPP. This formulation allows a 3-fold reduction, over the once-a-month depot, in the number of i.m. injections required each year.

Objective: to review the potentid applications of photodynamic therapy (PDT) in gynaecology, using 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) photosensitization. Methods: relevant publications were retrieved by searches on Medline between 1986 and 1996 using the following MeSH headings: 5-aminolevulinic acid, photofrin, haematoporphyrin derivative, endometrium, photodynamic therapy or using a combination of the above. References were also obtained from reference lists of known sources. Results: photodynamic therapy using ALA appears to offer the potentid of a simple, non-surgical approach to ablation of the endometrium. Its application as an office procedure would provide a major advance for women suffering from menorrhagia, and could eliminate the unwanted withdrawal bleeding experienced by post-menopausal women on hormone replacement therapy (HRT). Photodynamic therapy could be used to treat ectopic pregnancies in cases where laparoscopy is needed for diagnosis, and has the potentid for the detection and treatment of endometriosis. Photodynamic therapy has been employed for palliative treatment of advanced gynaecologic alignancies and may play a role in treating benign vulvar and vaginal lesions, for example, condylomata. Conclusions: 5-aminolevulinic acid-induced PpIX photosensitization has the potentid to play a significant role ingynaecology due to its specificity for desired target tissues in the pelvis. The major clinical applications of ALA-PDT are likely to be the ablation of the endometrium in women suffering from menorrhagia and the simplification of HRT in post-menopausal women.

Swyer syndrome also known as 46XY complete gonadal dysgenesis is a rare cause of primary amenorrhea. These patients are phenotypically females with female type of internal and external genitalia with absence of testicular tissues. They have streak gonads which have increased potential to turn into malignancy. Bilateral gonadectomy should be done as soon as diagnosis is made. In present case, 20 years unmarried female came with complaints of menstrual bleeding only on taking medication. She never attained menarche, following which she was started on treatment outside, on withdrawal bleeding for the past 3 years. She was now evaluated and diagnosed as Swyer syndrome and bilateral gonadectomy was done laproscopically. Swyer syndrome patients can get married, have normal sexual life and can get pregnant through invitro fertilisation with donor oocyte if desired.

In 2007, the FDA approved Lybrel (U.S. Food and Drug Administration 2007), the first oral contraceptive pill (OCP) designed to completely eliminate the monthly withdrawal bleeding periods associated with birth control pills. Pharmaceutical technology has made it possible for women to choose not to menstruate for a host of reasons, includ- ing menstruation-related medical conditions, gender dysphoria, and personal convenience. This practice has faced a great deal of opposi- tion from factions of the feminist community, medical professionals, women’s health advocates, and others, for reasons often rooted in prob- lematic notions of menstruation as essential to “natural” and “normal” womanhood. In Chapter 4 of this book, Fahs examined the moral panic that ensues when menstruation is exposed to the public eye through student activism. This chapter, by contrast, will demonstrate that the absence of menstruation can also prove panic-inducing. In essence, women’s bodies serve as a source of panic regardless of the choices they make regarding menstruation.

In terms of our understanding of menopause and hormone replacement therapy, 1993-1994 did not see any seminal or definitive publications. However, the data that were published have helped refine our understanding of the benefits and risks of hormone replacement therapy. This article presents further evidence for the protective effects of hormone replacement therapy in preventing osteoporosis and arterial disease, including direct gonadal hormone effects upon the vessel wall; discusses changes in attitudes to progestogen additions, withdrawal bleeding and endometrial status; reviews controversies over the relationship between hormone replacement therapy and breast cancer risk, and briefly mentions a new device for delivery of non-oral oestradiol.

Objective To assess compliance with recommendations for hormone replacement therapy (HRT) in postmenopausal women following screening for osteoporosis. Design A postal questionnaire sent to women an average of 8 months (range 6–12) following measurement of their bone mineral density (BMD), and recommendations regarding HRT given to the referring general practitioner. Setting Referrals from local general practitioners. Mixed social class. Subjects 400 postmenopausal women aged 40–69 years (average age 52). Main outcome measures Compliance with advice and if failing to comply, reasons for not doing so. Results Replies were received from 352 women (88%) and 74% of respondents followed advice to start, continue, or refrain from starting or continuing HRT with regard to protecting their skeleton. Those who rejected advice to take HRT mostly had concern over side effects or the efficacy or safety of treatment. Of the women who started HRT 28% subsequently stopped, the principal reasons being withdrawal bleeding and weight gain. Of the women recommended to take HRT, 39% were not taking treatment by 8 months after referral, either because they ignored advice given (22%) or because of side effects (17%). Conclusions Screening leads to increased usage of HRT among women at most risk for osteoporosis. However, almost 40% of women with low bone mineral density were not taking HRT 8 months after referral, and therefore until improved compliance has ben demonstrated screening cannot be widely recommended.

One hundred fifteen women under age 40 presenting with hypergonadotropic amenorrhea (follicle-stimulating hormone greater than 40 mIU/mL) were evaluated. Incomplete pubertal maturation and chromosomal abnormalities were more likely in the 18 women (15.7%) with primary amenorrhea than in those with secondary amenorrhea. The 97 women with secondary hypergonadotropic amenorrhea were significantly more apt to complain of symptoms of estrogen deficiency, have been pregnant before diagnosis, and have evidence of ovulation after diagnosis. Withdrawal bleeding occurred commonly (greater than 48%) in those women administered exogenous progestin. Immune abnormalities occurred with approximately equal frequency (17.4%), and spinal bone density was decreased in both groups.

A postmenopausal woman, receiving cyclic hormonal therapy, presented to our clinic with acute pelvic pain, absence of withdrawal bleeding and clinical signs of vagal stimulation (nausea and vomiting). Vaginal exploration and ultrasonographic imaging accounted for haematocervix, which was confirmed by surgical blood evacuation.

Surgically menopausal women are 5 times more likely to begin hormone replacement therapy than are naturally menopausal women, and they continue therapy for longer periods. The primary reasons that women refuse hormone replacement are fear of cancer and perceived side effects. In contrast, withdrawal bleeding is the major reason that women discontinue hormone replacement therapy. Physician-patient communication plays an important role in a woman's decision to use hormone replacement therapy, to fill her prescription, and to adhere to the regimen. The first visit at which hormone replacement therapy is discussed is crucial to establishing an effective patient-physician relationship. At least 15 minutes, and preferably 45 minutes, should be reserved for this visit. Patient follow-up-either by phone or in person-during the first month can help improve adherence because this is when many women may have nuisance side effects and discontinue therapy.

Objective: To describe a technique for surgical management of complete obliteration of the endometrial cavity. Design: A report of a series of three patients. Setting: A university-based hospital. Patient(s): Three patients with complete obliteration of the endometrial cavity. Intervention(s): Transfundal scar removal using stents in the fallopian tubes to serve as landmarks. Main Outcome Measure(s): Regular withdrawal bleeding. Result(s): Regular menses in all three patients. Conclusion(s): The technique described here shows promise for establishing uterine cavity integrity in cases of complete endometrial obliteration where there are no landmarks in the uterine cavity.

Tibolone (Livial) has advantages over other forms of hormone replacement therapy (HRT); it is easy to use and does not induce withdrawal bleeding in postmenopausal women. The evidence for the effect of tibolone on climacteric symptoms is reviewed and shows that tibolone is effective in reducing vasomotor symptoms and vaginal dryness. Tibolone's effect on a range of other symptoms such as headache and insomnia is unclear. There are reports that tibolone improves mood and libido but much of this research is methodologically flawed. Methodologically sound research is required to investigate tibolone's effect on mood and libido; such a study is in progress.

Objective: To determine the response to the progestin challenge test on endometrial thickness 40 UI/ml and Estradiol

The objective of the study was to assess the opinion of women about the use of hormone replacement therapy (HRT) in relation to continuation or re-induction of bleeding periods after menopause. The design was a population-based cross-sectional study using a postnatal questionnaire in Krimpen aan den IJssel, a commuter suburb of Rotterdam. The participants were all 2729 women living in Krimpen aan den IJssel aged 45-60 years, of whom 1947 (71.3%) responded. The main outcome measure was an opinion on monthly or trimonthly withdrawal bleedings with HRT. The results showed 16.9% of all women have no or little objection to use of HRT with monthly withdrawal bleedings. There is a marked difference between premenopausal women (32.4% have no or little objection) and postmenopausal women (only 9.2% have no or little objection). Trimonthly cycles during HRT tend to be perceived as more acceptable (41.4% of premenopausal women and 11.8% of postmenopausal women have no or little objection). It is concluded that a reasonable proportion of premenopausal women accept continuation of periodic bleeding with HRT. There is a preference for trimonthly cycles rather than monthly withdrawal bleedings. Most postmenopausal women object to having withdrawal bleedings with HRT, irrespective of a monthly or trimonthly cycle. Research should continue on schedules without withdrawal bleedings.

A 2-year prospective study was conducted on 44 early postmenopausal women to assess the effect of transdermal estradiol (TTS-E2) on vertebral bone mass. Twenty treated women and 24 untreated were studied. Treatment consisted of TTS-E2 and an oral gestagen. The findings suggest that low doses of transdermal estradiol sufficient to relieve menopausal symptoms, and which, due to the association with progestogen, result in regular withdrawal bleeding, are effective in preventing postmenopausal bone loss

Twenty-six women, most of them with advanced endometriosis (Stage III according to Acosta), were treated for six months with the LH-RH agonist Buserelin. After initially increased liberation both of the gonadotropins as well as of the sexual steroids there was consecutive inhibition of gonadal function, especially after inhibition of FSH secretion. Within two to four weeks estradiol production was completely and lastingly suppressed in 21 of the 26 women. In three women it lasted for three months and in two women estradiol again rose up to three times during the period of observation. Correspondingly, 22 of the women suffered from hot flushes as early as within the first two months. Twenty of the 26 women became completely free of symptoms within four to six weeks, and a clear regression of the pain was recorded in another four. In two women the complaints persisted without change. Withdrawal bleeding of short duration occurred simultaneously with the intermittent increases in estradiol levels; however, this bleeding usually caused little or no pain. Eleven of the 19 endometrium biopsies performed during therapy revealed a dormant endometrium, and only in one case was proliferated endomedium found, in the third month of treatment, in a stage of transition to hyperplasia. The remaining seven biopsies were insufficient for assessment. In seven women with advanced endometriosis, laparotomies were performed after drug treatment. Histologic study of the endometriosis tissue thus obtained revealed, except in the two nonresponders, cicatrized tissue with atrophic glands and severely reduced stroma.(ABSTRACT TRUNCATED AT 250 WORDS)

One hundred and sixty-five women were treated during a total of 3,281 cycles with Neo-Lyndiol, a combined oral contraceptive containing 2·5 mg lynestrenol and 0·050 mg ethinyloestradiol per tablet. The tablets were taken for 32 days, with six tablet-free days. No pregnancies were seen and the proportion of patients experiencing irregular bleeding and side-effects was very low and in fact their complaints decreased considerably as medication continued. There was a drop-out rate of only 5·5%, which is exceptionally low. Neo-Lyndiol proved to be a reliable preparation, controlling the cycle well and causing few side-effects.

• Because the significant health risks related to postmenopausal osteoporosis can be reduced by estrogen replacement therapy (ERT), this study assessed women's attitudes toward ERT to assess factors that might increase its use. Results showed that women taking ERT were more likely to know that decreased estrogen levels lead to osteoporosis, to perceive that menopause is a medical condition, to believe that natural approaches to menopause are less preferable, to be seeing a gynecologist for care, and to believe that women should take ERT for hot flashes. The study suggests that a systematic educational approach could influence women's willingness to take ERT, especially if the recommended therapy does not cause withdrawal bleeding. ( Arch Intern Med 1989;149:133-136)

The suppression of cyclical ovarian activity by subcutaneous implants of oestradiol has been used to treat the premenstrual syndrome (PMS) in 92 patients, including 16 who also suffered from menstrual migraine. The treatment, usually with an initial dose of 100 mg oestradiol, reduced to 50 mg every 6 months, has continued for upto 7 years, with a mean duration of therapy of 2.0 years; 80% of patients have had more than one implant, and 32% have had five or more. Complete or almost complete relief of the symptoms of the PMS was reported by 84%. Previous medication was reduced or discontinued by 83%. Of the 84% where a comparison could be made with previous treatments, 93% considered implant therapy to be the most effective.Progestogen was given cyclically, usually for 7-10 days each month, to induce regular withdrawal bleeding and prevent endometrial hyperplasia. This was associated with the return of the patients' characteristic premenstrual symptoms in 45%, but to a lesser degree and for a shorter durati...

SummaryA menopause clinic has been established as part of the National Health Service at the Birmingham and Midland Hospital for Women. An investigation was made into 112 women accepted for treatment during the first year. Treatment consisted of mestranol and norethisterone in a graded 28-day cycle. Treatment was maintained for 6 cycles. Patients were assessed on admission, at intervals during treatment, and 2 months after therapy was completed.Hot flushes and all other common menopausal symptoms were reduced on treatment. All symptoms returned when therapy was discontinued. The treatment stimulated regular light withdrawal bleeding. No breakthrough bleeding occurred. Two women with other predisposing factors developed superficial thrombophlebitis of the calf. Breast tenderness, nausea and cramps were minor side-effects. Fifteen women dropped out.Treatment resulted in decreases in the serum values for sodium, urea, total protein, albumin, calcium, alkaline phosphatase, SGOT and cholesterol. Triglyceride v...

The treatment of anovulatory, clomiphene-resistant patients with polycystic ovarian disease (PCOD) is difficult. Ten such women were given progesterone, 50 mg/day i.m. for 5 days to achieve luteal phase concentrations. Immediately following progesterone treatment, plasma concentrations of FSH were reduced in all patients (P = 0.001) and seven of the 10 had reduced plasma LH concentrations. Following the withdrawal bleeding these seven all became responsive to clomiphene as shown by ovulation, and three conceived after a single progesterone/clomiphene cycle. LH pulsatility, studied in five women over 4 h, before and immediately following progesterone treatment, showed a slowing of the pulse frequency (62 +/- 26 min to 105 +/- 51 min, P less than 0.05) and an increase in pulse amplitude (6 +/- 1.9 IU/l to 16.7 +/- 20 IU/l). The LH and FSH response to GnRH was blunted by progesterone. It would thus appear that progesterone modulates LH pulsatility and reduces pituitary sensitivity to GnRH, reducing LH levels and possibly inducing more FSH synthesis and storage, similar to its action in the normal ovulatory cycle. These changes provide a more favourable environment for ovulation induction by clomiphene and we suggest that short-term progesterone treatment may be utilized to improve the efficiency and results of clomiphene treatment in PCOD.

Twelve immature female monkeys were treated with varying amounts of pregnant mare's serum gonadotrophin (PMSG). Seven of these monkeys responded to PMSG treatment as shown by sex skin development, ovarian enlargement and withdrawal bleeding. These animals reached menarche between 23 and 26 months of age, almost 1 year earlier than untreated control monkeys. Five other animals did not show an initial response to PMSG treatment and attained puberty simultaneously with the untreated animals. It is suggested that increased production of oestrogen by the PMSG-stimulated ovaries may affect the hypothalamo-hypophysial axis in such a way that puberty is accelerated.

A two-year study of estrogen replacement therapy was conducted on 1,200 postmenopausal women. Computerized data concerning the effect on 20 common symptoms showed 95 per cent relief during an appropriate regimen of estrogen-progesterone therapy. The improvement in the ability to enjoy life counteracted any reluctance to undergo hormone-induced withdrawal bleeding in the women with an intact uterus. There was no laboratory or clinical evidence that the treatment caused cancer. The benefits of continuous cyclic hormone therapy for estrogen-deficient women far outweigh the possible dangers.

An analysis of vasomotor, psychological, and physical symptoms of 136 women who were receiving piperazine oestrone sulphate (Ogen) and conjugated equine oestrogens (Premarin) after menopause has shown differences in responses which can be explained only if it is accepted that the two oestrogenic compounds have differing effects on various parts of the body. Premarin (0.625 mg) was found to be more potent at inducing withdrawal bleeding than Ogen (1.25 mg), whereas Ogen was more effective than Premarin in alleviating hot flushes and some psychological symptoms. A hypothesis involving metabolism of oestrone to the catecholamine, 2-hydroxyoestrone, is postulated, which explains why these differences occur. It is further suggested that better selection of oestrogens to suit particular postmenopausal symptoms should be encouraged when prescribing oestrogen for women after menopause.

The effects of mixed synthetic estrogens ∗ ∗The following formula is the one used: was studied for the past four years in a group of 105 cases of menopause. The following results were obtained: 1.1. Freedom of symptoms for approximately four months. 2.2. No toxic reactions. 3.3. Three cases of withdrawal bleeding. 4.4. Synergistic action between the dimethoxy stilbestrol and stilbestrol.

Summary: A trial was undertaken with 2 single-dose drugs for the inhibition of postpartum lactation. Two hundred patients were studied, of whom one half were given a single oral tablet of quinestrol (Estrovis) 4 mg. and the other half were given a single intramuscular injection of Ablacton. The results showed that both preparations were equally effective in the initial inhibition of lactation and were rarely associated with rebound breast engorgement or withdrawal bleeding.

2 oral progestogens: 6-alpha-methyl-17-hydroxyprogesterone acetate alone (oragest) and with added ethinyl estradiol (nogest); and 17-alpha-ethinyl-17-hydroxy-5(10)-estren-3-one with added ethinyl-estradiol-3-methyl-ether (Enavid); were used in 86 women for inhibition of lactogenesis. The progestogen-estrogen combinations proved to be most effective. Enavid appeared to inhibit lactogenesis most strongly. Nogest seemed to be almost as potent while the pure progestogen Oragest was definitely inferior. Ethinyl-estradiol used at .3mg as a control in this trial effectively prevented engorgement and breast pain but did not prevent lactogenesis. In the patients with 2 weeks follow-up no rebound or withdrawal bleeding was observed. Persistent lochia rubra were reported by about a third of these patients.

Psychological factors are the most common cause of menstrual dysfunction. Emotionally-induced disturbance at the hypothalamic level can lead to irregular cycles, dysfunctional uterine bleeding, or amenorrhea. Mild disturbances are usually associated with an ample amount of endometrial lining, and a period of withdrawal bleeding can usually be produced with progesterone. Where there is a deficiency of estrogen and consequently insufficient endometrial lining for withdrawal bleeding, organic pituitary and/or hypothalamic disease must be excluded. The psyche can also influence the uterus and ovary directly.

Oestrogen therapy, and later on oestrogen — progestogen sequential therapy, of the climacteric syndrome in the menopause and postmenopause has been given to a growing number of patients over the last few decades, notwithstanding the fact that the many problems that this therapy brings along are far from being solved.

In 1966 Neumann and Elger1 first showed that the anti-androgen cyproterone acetate (CPA) reduced the output of the sebaceous glands of mice. This interested those involved in the treatment of acne. The first regime to be used in women was the ‘reverse sequential’ regime of Hammerstein2 who gave 100mg of CPA from day 5 to day 15 of the cycle and 50μg of oestrogen from day 5 to day 26. This regime was used to ensure that withdrawal bleeding occurred on completion of the cycle, because of the strong progestrogenic effect, and depot storing of this high dose of CPA. This method of treatment was found to be successful, with rates of response of 70 per cent improvement after 3 months of treatment being claimed. However, because of the potent unphysiological effect of this dose of CPA, a lower dose combination preparation was developed as an oral contraceptive with 2mg of CPA and 50μg of ethinyloestradiol (Diane, Schering).

We have studied growth and adrenal dehydroepiandrosterone (DHA) responses to iv synthetic adrenocorticotrophic hormone (ACTH, Cortrosyn) in 6 girls with gonadal dysgenesis before and during treatment with lowdose ethinyloestradiol (EOe2). In all patients there was a statisfactory induction of secondary sexual characteristics including increase in breasts and pubic hair and onset of withdrawal bleeding within 6 months of therapy. Height velocity increased from 2.8 ± 0.9 cm/year pre-treatment to 5.3 ± 1.5 cm/year (P < 0.02) in the first year. There was deceleration to 1.9 ± 1.1 cm/year in the second year. There was no disproportionate advancement in bone age and thus, presumably, no loss of ultimate height. We could demonstrate no change in basal or ACTH-stimulated levels of DHA, a specific adrenal androgen, to account for the increased pubic hair and growth in these patients.

1. 1. The daily injection of 15,000 rat units (2.5 mg.) estradiol benzoate and 12.5 mg. progesterone for three days was used as a pregnancy test on fifty-six patients with amenorrhea of less than six months' duration. 2. 2. Withdrawal bleeding was produced in all of the nonpregnant women. None of the pregnant patients bled except for one who spotted very scantily on one day. 3. 3. The method described appears safe and accurate for use as a pregnancy test.

IN accord with the recent trend in endocrine replacement therapy toward a depot effect, studies are being reported on comparisons of the relative effects of the various steroid hormones in aqueous crystalline suspension and in oily solution. The literature on this subject is still small and is chiefly limited to work on animals. The following experiments were designed to test the comparative activity of an aqueous crystalline suspension of progesterone, and a solution of progesterone in sesame oil, in elderly postmenopausal women. Estrogen and progesterone withdrawal bleeding in many patients well past the menopause has been previously demonstrated (1). The criterion established for comparing the biologic activity of various preparations having luteal activity, namely, the capacity to produce withdrawal bleeding under certain dosage schedules, was followed in the present study. The production of uterine bleeding by this method is dependent upon progesterone deprivation in the presence of sustained estroge...

Almost 5% of women is affected by irsutism and about 55% of these subjects start complaining on some signs during the adolescence period in which a considerable anxiety is connected with the body image. After having excluded Cushing's syndrome, CAH late onset, ovarian and adrenal turnours, we treated six adolescents (mean age 16yr 1mo)affected by hirsutism (Hatch's score ≥ 10) with 100 mg/daily of spironolactone for 12 months (200 mg/daily with score > 20 or therapeutical unsuccess after 6 months of therapy). To all subjects was added an oral contraceptive (0.15 mg of descgestrel + 0.03 mg of ethinil -estradiol) to obtain regular withdrawal bleeding and contraception effect. To make a correct evaluation of the data, we excluded from the study those areas treated by esthetic treatment. Clinical and hormonal evaluations (FSH, LH, PRL, T, DHEAs) were obtained before and after 3-6-9-12 months of therapy. During follow-up no change was demonstrated in hormone levels; the mean score significantly decreased after 3 months of therapy (p < 0.01) and at every specific control (p < 0.001). In one girl, 6 months off-therapy, no sign of hirsutism was demonstrated. No significant side-effects were noted in our patients. Spironolactone combined to an cstro-progestagen is an effective and well-tolerated approach to the smanagement of hirsutism in adolescents.

Hyperprolactinemia is recognized commonly as a cause of menstrual dysfunction and hypogonadism in adults but is often assumed to be rare in adolescents. The clinical features of this in adolescence have not been well characterized. We have studied 20 patients with adolescent onset of hyperprolactinemia. Initial results on 16 (13 females and 3 males) are as follows: The cause of hyperprolactinemia was microadenoma in 6, macroadenoma in 7, pituitary cyst in 1 and tumor hydrocephalus in 2. Onset was between 9 and 19 years with a mean of 14.6 years but the diagnosis was delayed almost 5 years to a mean age of 19.3 years. Prolacting levels varied from 33 to 3450 ng/ml. Presenting complaints in females were: Amenorrhea in 64%, galactorrhea in 18%, cystic acne in 9%. Galactorrhea was present in 73% but only 1/3 of these were aware of it. Headaches were present in 82%. 6 of 8 patients had withdrawal bleeding after Provera. 3 patterns of pubertal progression were seen: 1)primary amenorrhea 18%, 2)normal menarche with only a few periods 36%, 3) normal menarche, irregular menses for several years and amenorrhea in 46%. 4 of 5 patients with macroadenomas have had surgery, radiotherapy or both and 3 of these have residual hyperprolactinemia and other residua. Although hyperprolactinemia is a common cause of menstrual or pubertal disturbance in adolescence, diagnosis is usually delayed. Because outcome is often suboptimal, an effort toward timely diagnosis is indicated.

The inhibition of lactation by prescribing free fluid intake described by Mr. C.K. Vartan (4 January p. 50) is a most satisfactory method of suppression. The disadvantages of the stilboestrol method the secondary engorgement of the breasts and the withdrawal bleeding which sometimes occur are eliminated. It would appear now that the risk of venous thrombosis is greatly reduced. Free fluids have been used for a considerable time as the sole method of suppression of lactation in out maternity unit and we have found it most effective. Stilboestrol does not appear to have any superior advantage. I can recommend the free fluid technique to Dr. D.D. Brown (4 January p. 50) as a thoroughly satisfactory replacement for stilboestrol in the suppression of lactation. (Full text)

To the Editor:— In current medical and lay literature, a number of authors have expressed opinions on the necessity for continuous estrogen treatment in women. Some believe that for physiological and cosmetic reasons every woman should receive routine estrogen therapy throughout life and not only at menopause or when clinically indicated. Pleas have been made for adequate estrogen therapy from "puberty to grave" and plans have been described for administration of these drugs. 1 Hormones were to be administered to all aging women in a cyclic manner so that withdrawal bleeding would occur regularly. The menopause would thus be eliminated and femininity would be preserved. On the heel of these publications a pharmaceutical company responded with an energetic sales promotion to acquaint physicians with their hormone products. Working regimens were outlined for cyclic replacement therapy. 2 Dosage level of estrogens was to be guided by the type of exfoliated cells