Drug-Induced Hypertension
Giuseppe Mancia, Guido Grassi, Konstantinos P. Tsioufis, Anna F. Dominiczak, Enrico Agabiti Rosei in Manual of Hypertension of the European Society of Hypertension, 2019
Testosterone leads to androgen receptor agonism, which will elevate BP through the resulting salt and volume retention. This is not seen when testosterone is given to men with hypogonadism. Indeed, in this group, BP improves by 23/16 mmHg and there is a reduction in cardiovascular risk (22). Anabolic androgenic steroids are synthetic molecules derived from testosterone and are used in various medical conditions. They are also used by people to enhance exercise performance and for cosmetic reasons. They can lead to hypertension and other cardiovascular abnormalities; for example, left ventricular dysfunction, aortic stiffness and atherosclerosis (23,24). Aortic stiffness may persist years after discontinuation of androgens, leading to increased cardiovascular risk (24). Taurine helps to attenuate these effects in animal models (23). Danazol is a semisynthetic androgen used in the management of endometriosis and hereditary angioedema. It is also a performance-enhancing drug misused by exercise enthusiasts. It can lead to elevated BP, which resolves on discontinuation.
The twentieth century
Michael J. O’Dowd in The History of Medications for Women, 2020
The next treatment of note was that of ‘pseudomenopause’. Greenblatt and associates (1971) introduced danazol which brought about a hormonal state similar to chronic anovulation. As a result, the endometriosis implants atrophied. Danazol bound itself to the progestin, androgen and glucocorticoid receptors. Its net effect was the creation of a high-androgen, low-estrogen environment that was detrimental to endometrial growth. Unfortunately the side-effects of danazol were common and primarily due to its androgenic properties. Despite this, the patients who persisted with treatment reported that danazol was effective in alleviating endometriosis-associated pain. A number of other steroid and anti-steroid treatments have been used, including gestrinone, tamoxifen and the synthetic RU486.
Thromboembolic Disease in the Obstetric Patient: Evaluation, Diagnosis, and Treatment
Hau C. Kwaan, Meyer M. Samama in Clinical Thrombosis, 2019
The ideal prophylactic regimen for the pregnant patient is as yet unsettled. Danazol is contraindicated during pregnancy. Two basic regimens with some variation have been employed. The first is to institute subcutaneous heparin prior to conception and then substitute oral anticoagulants from 13 until 36 weeks gestation. At this time, heparin is reinstituted. The second is to avoid the known fetal (as opposed to embryonic) effects of warfarin-like agents and continue the heparin throughout gestation. AT III concentrate may be used in the event of thrombosis and/or during labor. This author recommends the latter method. Fresh-frozen plasma is a less satisfactory alternative to AT III concentrate. All patient series are small, but the success rates appear similar.32,33,71–73 The general consensus of the participants at the 1st World Symposium on Antithrombin III Deficiency, West Berlin, 1987 was that oral anticoagulants are avoidable.84
Conservative treatment of deep infiltrating endometriosis: review of existing options
Published in Gynecological Endocrinology, 2018
Maria Szubert, Magdalena Ziętara, Jacek Suzin
Danazol is a synthetic steroid (17α-ethinyltestosterone derivative) that acts by inhibiting steroidogenesis and by increasing free testosterone levels. It has antigonadotrophic effects on the pituitary. It has efficacy in suppressing normal endometrial growth and in causing atrophy of deposits of endometrium [41]. Danazol competitively inhibits aromatase activity in endometriosis-derived stromal cells without affecting either the mRNA or protein levels of aromatase. Danazol has been shown to be effective in treating endometriosis, leading to remission [42,43]. Therapy is generally well-tolerated by the patients, however, there are reported side effects like: acne, oily skin, seborrhea, water retention, hirsutism, hot flushes, and atrophic vaginitis which often led to discontinuation of treatment [44]. Nowadays, it is most common to use vaginal danazol which can be administered by ring, gel and capsule. This therapy has effectiveness in DIE resulting in a cure of dysmenorrhea and tenderness in cul-de-sac within 3 months and induration or nodularity in the cul-de-sac within 7 months. Positive aspects of this treatment are: undetectable serum danazol concentrations (which implies with possibility of ovulation and conception occurrence in infertility women), no endometrial atrophy, absorption of danazol through the vaginal mucosa and reaching the DIE via diffusion [45].
Drug-induced arterial hypertension – a frequently ignored cause of secondary hypertension: a review
Published in Acta Cardiologica, 2018
Camelia Cristina Diaconu, Giorgiana Nicoleta Dediu, Mihaela Adela Iancu
Studies on women taking oral contraceptives have shown that hypertension is 2–3 times more frequent than in control subjects [3]. Women with a family history of arterial hypertension or a personal history of pregnancy-induced hypertension have increased risk, as well as smokers, obese, or diabetic women [4]. This increased risk of hypertension associated with oral contraceptives is explained by the natrium retention, with increased volemia due to the effects on mineralocorticoid receptors, or by increased serum concentrations of angiotensinogen [5]. The risk of hypertension increases parallel with the doses used. Estrogen replacement treatment in post-menopausal women may slightly increase the blood pressure values. Also, treatment with oestrogens for prostatic cancer in men may be associated with increased risk of hypertension. Danazol is a semisynthetic androgen drug recommended for women with endometriosis or for patients with hereditary angioedema; this drug produce natrium and water retention, with elevations of blood pressure values [6].
The role of pharmacotherapy in the treatment of endometriosis across the lifespan
Published in Expert Opinion on Pharmacotherapy, 2020
Kaia Schwartz, Natalia C. Llarena, Jenna M. Rehmer, Elliott G. Richards, Tommaso Falcone
Data specific to the postoperative management of deeply infiltrating endometriosis (DIE) are limited; however, some studies have reported improvements in recurrence rates with postoperative medical treatment [45]. In a prospective cohort study of 500 women who underwent rectal shaving for DIE involving the bowel, the recurrence of pelvic pain occurred in 13% of women treated with continuous COCs or progestins compared to 20% of those who were not treated. The lowest recurrence rate was among women who became pregnant after surgery and immediately began continuous progestins after delivery (2%) [46]. Danazol may also have a role in postoperative suppression for women with DIE, though its utility is limited by side effects; danazol is not frequently prescribed in its oral form. A randomized trial of 60 patients evaluated danazol 200 mg 3 times daily for 6 months after laparoscopy and demonstrated significant improvements in postoperative pain compared to placebo [47]. A second-look laparoscopy at 6 months showed a reduction in the size of recurrent endometriotic implants after danazol treatment. While androgenic side effects are common in oral danazol treatment, including acne and weight gain, recent studies of vaginal or intrauterine danazol have reported substantial improvements in pain associated with DIE with no systemic side effects [48].
Related Knowledge Centers
- Acne
- Hirsutism
- Virilization
- Endometriosis
- Fibrocystic Breast Changes
- Hereditary Angioedema
- Oral Administration
- Side Effect
- Voice Change
- Mechanism of Action