Norethindrone Acetate-Ethinyl Estradiol for Oxytocin Deficiency

Recruiting in Palo Alto (17 mi)

Overseen by Elizabeth A Lawson, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

Sponsor: Elizabeth Austen Lawson

Disqualifiers: Pulmonary embolism, Cancer, Stroke, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This is an open-label, pilot study, to characterize oxytocin response to a single dose of oral Estrogen-progestin in patients with arginine-vasopressin deficiency compared to healthy controls. The association between oxytocin levels and measures of psychopathology (i.e., anxiety and depression) and quality of life across groups will be examined. We hypothesize that: 1. Salivary and blood oxytocin response to Estrogen-progestin will be lower in arginine-vasopressin deficiency compared to healthy control. 2. Lower salivary and blood oxytocin levels will be associated with more severe symptoms of anxiety, depression, and social emotional difficulties as well as lower quality of life.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

Is Norethindrone Acetate-Ethinyl Estradiol generally safe for humans?

Norethindrone Acetate and Ethinyl Estradiol, commonly used in oral contraceptives, have been shown to have low toxicity in both short-term and long-term use. While some studies in animals showed an increased risk of tumors, this was not observed in monkeys, and these hormones are not known to cause birth defects when used together. Overall, they pose very little health risk to humans.

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How does the drug Norethindrone Acetate-Ethinyl Estradiol differ from other treatments for oxytocin deficiency?

Norethindrone Acetate-Ethinyl Estradiol is unique because it combines two synthetic hormones commonly used in oral contraceptives, which are now being explored for other therapeutic uses. This combination has been shown to have low toxicity and minimal health risks with long-term use, making it a novel approach for conditions like oxytocin deficiency where standard treatments may not exist.

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Eligibility Criteria

This trial is for adults aged 18-65 with arginine-vasopressin deficiency who are on stable pituitary hormone replacement therapy. It also includes a control group of healthy adults within the same age range.

Inclusion Criteria

I am between 18 and 65 years old with stable hormone therapy for pituitary issues.

I am between 16 and 65 years old and healthy.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of oral Estrogen-progestin to assess oxytocin response

1 day

1 visit (in-person)

Follow-up

Participants are monitored for changes in oxytocin levels and associated psychopathology measures

48 hours

2 visits (in-person)

Participant Groups

The study tests how patients with arginine-vasopressin deficiency respond to a single dose of oral Estrogen-progestin compared to healthy controls, and examines the link between oxytocin levels, psychopathology symptoms like anxiety and depression, and quality of life.

Group I: Healthy control Experimental Treatment 1 Intervention

Norethindrone Acetate-Ethinyl Estradiol will be given to the healthy controls.

Group II: Arginine-vasopressin deficiency Experimental Treatment 1 Intervention

Norethindrone Acetate-Ethinyl Estradiol will be given to participants with arginine-vasopressin deficiency

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Massachusetts General Hospital Boston, MA

Who Is Running the Clinical Trial?

Elizabeth Austen Lawson Lead Sponsor

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Pharmacology and toxicology of ethinyl estradiol and norethindrone acetate in experimental animals. [2018] For over 30 years various combinations of synthetic estrogens and progestins have been used in oral contraceptive formulations. Ethinyl estradiol (EE) and norethindrone acetate (NA) are common synthetic hormones used in oral contraceptives such as Loestrin, Brevicon, Ortho-Novum, Norlestrin, and Norinyl. In recent years these oral contraceptives have been considered for development in other therapeutic indications. Given the use of these agents for other clinical indications with different and larger target populations, an updated comprehensive review of the toxicology literature of estrogens and progestins is warranted. This review will summarize available data on the pharmacology and toxicology of estrogens and progestins with an emphasis on the specific synthetic hormones EE and NA. Ethinyl estradiol and norethindrone acetate alone or in combination, possess low acute and chronic toxicity. In some studies, EE and/or NA increased the incidence of specific tumors in susceptible strains of rodents and dogs, but not monkeys. These agents are not teratogenic when given in combination. Alone EE and NA have clastogenic properties. Overall, the animal data demonstrates that long-term exposure to EE and NA formulations pose very little health risks to humans.

2. United States pubmed.ncbi.nlm.nih.gov

The efficacy and tolerability of norgestimate/ethinyl estradiol (250 micrograms of norgestimate/35 micrograms of ethinyl estradiol): results of an open, multicenter study of 59,701 women. [2022] The efficacy and tolerability of a new oral contraceptive, norgestimate/ethinyl estradiol (250 micrograms of norgestimate/35 micrograms of ethinyl estradiol; Cilag GmbH Research, Sulzbach, Germany) were examined in an open-label study of 59,701 women who were evaluated during 342,348 menstrual cycles; 42,022 women completed the planned treatment regimen of six cycles. A use-efficacy (overall) Pearl index of 0.25 pregnancies per 100 woman-years was calculated based on 342,348 cycles. Tolerability was assessed for all women who completed six treatment cycles. Reductions in mean cycle length and duration of bleeding were noted; 32% of the women experienced reductions in the intensity of bleeding by the end of cycle 6. After six cycles of use, amenorrhea occurred in 1%, spotting in 4%, and breakthrough bleeding in 3% of the participating women. Treatment with norgestimate/ethinyl estradiol had minimal effects on weight, blood pressure, pulse, lipid metabolism, and blood glucose. Adverse effects (acne, nausea, or headaches) occurred at low frequencies and in many cases, were reduced compared with pretreatment levels. The results of this large-scale open trial were comparable with results from two other multicenter trials of the same formulation.

3. United States pubmed.ncbi.nlm.nih.gov

The optimal dose of oral norethindrone acetate for addition to transdermal estradiol: a multicenter study. [2019] The effects of adding one of three doses (0.5, 0.75, or 1.0 mg/d) of norethindrone acetate for 12 days each month to continuous, transdermal estradiol (0.05 mg/d) have been determined in a prospective, randomized, multicenter study. Significant symptomatic and psychological improvements were observed and, with one exception, were not opposed by the added progestogen. Distinct redness at the site of last patch application was reported by 10% of patients and faint erythema by 30%. However, less than 5% of patients discontinued treatment because of skin problems. Breakthrough bleeding occurred infrequently and all three doses of norethindrone acetate induced a regular pattern of bleeding with secretory transformation in the endometrium. There was no hyperplasia or carcinoma.

4. United States pubmed.ncbi.nlm.nih.gov

Oral contraceptives. [2017] Management of oral contraception requires an understanding of the relationships between the method's effectiveness, noncontraceptive benefits, and hormonal adverse effects. The new multiphasic combinations or OCs containing 35 micrograms of ethinyl estradiol and 0.5-1.0 mg of norethindrone or equivalent result in a maximum combination of efficacy and safety for the patient with minimal annoying problems for the patient and the prescriber. Patient education regarding early warning symptoms of adverse effects, breakthrough bleeding, and lack of withdrawal bleeding adds an additional margin of safety and reduces patient questions and uncertainties.

5. United States pubmed.ncbi.nlm.nih.gov

Norgestimate: a clinical overview of a new progestin. [2019] The efficacy and safety of a new monophasic oral contraceptive, norgestimate/ethinyl estradiol, containing the third-generation progestin, norgestimate (250 micrograms), and ethinyl estradiol (35 micrograms), are reviewed. Norgestimate/ethinyl estradiol demonstrates excellent contraceptive efficacy, with a Pearl index of 0.25. Cycle control is reliable, with a low incidence of breakthrough bleeding and spotting. Because of the minimal androgenicity of norgestimate, norgestimate/ethinyl estradiol has a low impact on carbohydrate and lipid metabolism. It neither reduces the vasodilatory and antiaggregatory prostacyclin nor increases its endogenous antagonist, thromboxane. Norgestimate/ethinyl estradiol has no significant effect on blood coagulation factors. All these characteristics suggest that norgestimate/ethinyl estradiol may be associated with a lower risk of cardiovascular disease than other oral contraceptives currently available. Epidemiologic data, however, are not available, and physicians should be reluctant to prescribe it or any oral contraceptive to patients who have a history of vascular or thrombotic disorders.

6. United States pubmed.ncbi.nlm.nih.gov

Safety and efficacy of a new oral contraceptive containing drospirenone. [2013] An oral contraceptive containing ethinyl estradiol and the unique progestin drospirenone provides a new contraceptive option. Ethinyl estradiol is the form of synthetic estrogen used in most oral contraceptives. Drospirenone differs from other synthetic progestins in that it is derived from 17 alpha-spirolactone and is an analogue of spironolactone. The oral contraceptive containing ethinyl estradiol and the unique progestin drospirenone has been shown to be highly efficacious and to provide safety equivalent to that of other oral contraceptive formulations.

7. England pubmed.ncbi.nlm.nih.gov

Radioimmunoassay of norethindrone (17 alpha-ethynyl-17 beta-hydroxy-4-estren-3-one) and ethynyl-estradiol (17 alpha-ethynyl-1,3,5, (10)-estratien-3, 17 beta-diol). Application to human plasma determination of norethindrone after oral administration of this steroid. [2013] The experiment conditions for the evaluation of Norethindrone (17 alpha-Ethynyl-17 beta-hydroxy-4-estren-3-one, NET) and Ethynyl-estradiol (17 alpha-ethynyl-1, 3, 5 (10) estratrien-3, 17 beta-diol, EE) by radioimmunoassay are described. A minimal quantity of 25 pg of these two steroids could be evaluated using different reduced metabolites of NET, very little cross reaction is observed with 200 pg of these metabolites. No effect was observed with estradiol for the EE-antiserum. The NET-antiserum was used to evaluate this steroid and ethynodiol diacetate after oral administration to female volunteers. Maximal values in the plasma (2-3% of the administered dose) was found between 1-3 h after administration and at 24 h a concentration of 0.1-0.3% still remained in the plasma.