Does Cenestin (conjugated estrogens) cause side effects?

Cenestin (conjugated estrogens) contains synthetic conjugated estrogens produced from plant material used as an external source and replacement for the natural female hormone. 

Estrogens have widespread effects on many tissues in the body. Estrogens cause growth and development of the female sexual organs and maintain female sexual characteristics such as the growth of underarm and pubic hair, body contours, and skeleton. Estrogens also increase secretions from the cervix and growth of the inner lining of the uterus (endometrium). 

Menopausal women produce less estrogen which leads to symptoms of hot flashes, vaginal dryness, shrinking in vaginal tissue and painful intercourse. Using conjugated estrogens can help treat such symptoms in menopausal women. Conjugated estrogens can also help in prevention of bone loss in menopausal women.

Common side effects of Cenestin include

Serious side effects of Cenestin include

Drug interactions of Cenestin include St. John's wort, phenobarbital, carbamazepine, and rifampin, which can accelerate the breakdown of conjugated estrogens, leading to low levels of absorbed drug and reduced effectiveness.

Cenestin is not recommended during pregnancy because it may cause birth defects in a fetus. 

Use of Cenestin is not recommended in nursing mothers because conjugated estrogens enter breast milk and may have harmful effects on the newborn. Conjugated estrogens can also affect the quality and quantity of breast milk. 

What are the important side effects of Cenestin (conjugated estrogens) ?

There are many side effects of conjugated estrogens. Common side effects of conjugated estrogens are

Estrogens can cause salt (sodium) and water retention (edema). Therefore, patients with heart failure or reduced function of their kidneys who are taking estrogens should be carefully observed for retention of water and its complications.

Blood clots in the legs (deep vein thrombosis or DVT) or lungs (pulmonary embolism) occasionally occur in women taking conjugated estrogens. This potentially serious complication of estrogen therapy is dose-related, that is, it occurs more commonly with higher doses.

Therefore, the lowest effective doses that relieve symptoms should be used. Cigarette smokers are at a higher risk for blood clots. Therefore, patients requiring estrogen therapy should quit smoking.

Estrogens can promote a build-up of the lining of the uterus (endometrial hyperplasia) and increase the risk of endometrial cancer. (Women who have undergone surgical removal of the uterus – hysterectomy - are not susceptible to endometrial hyperplasia.) The addition of a progestin to estrogen therapy prevents the development of endometrial cancer.

The Women's Health Initiative found that postmenopausal women (50 to 79 years old) taking conjugated estrogens, 0.625 mg daily, in combination with medroxyprogesterone (Provera, Depo-Provera, Depo-Sub Q Provera 104), 2.5 mg daily, for five years, had an increased risk of

Postmenopausal women taking conjugated estrogens without progesterone experienced only increased strokes but not increased

There was an increased risk of impaired cognition and/or dementia among women over age 65 treated with either estrogens or estrogens and medroxyprogesterone.

Cenestin (conjugated estrogens) side effects list for healthcare professionals

The following serious adverse reactions are discussed elsewhere in the labeling:

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In a 12-week clinical trial that included 72 women treated with 0.625 mg and 2 x 0.625 mg Cenestin and 48 women treated with placebo, adverse reactions that occurred at a rate of ≥ 5 percent are summarized in Table 1.

Table 1: Number (%) of Patients with Adverse Reactions with ≥ 5 Percent Occurrence Rate By Body System and Treatment Group

Body System
Adverse Reaction
Cenestina
0.625 mg and 2 x 0.625 mg
n=72
Placebo
n=48
Total
n=120
Any Adverse Reaction (%) 68 (94) 43 (90) 111 (93)
Body As A Whole
  Abdominal Pain 20 (28) 11 (23) 31 (26)
  Asthenia 24 (33) 20 (42) 44 (37)
  Headache 49 (68) 32 (67) 81 (68)
  Pain 8 (11) 9 (19) 17 (14)
Digestive System
  Dyspepsia 7 (10) 3 (6) 10 (8)
  Flatulence 21 (29) 14 (29) 35 (29)
  Nausea 13 (18) 9 (19) 22 (18)
  Vomiting 5 (7) 1 (2) 6 (5)
Metabolic and Nutritional
  Peripheral Edema 7 (10) 6 (13) 13 (11)
Nervous System
  Depression 20 (28) 18 (38) 38 (32)
  Dizziness 8 (11) 5 (10) 13 (11)
  Insomnia 30 (42) 23 (48) 53 (44)
  Leg Cramps 7 (10) 3 (6) 10 (8)
  Paresthesia 24 (33) 15 (31) 39 (33)
  Vertigo 12 (17) 12 (25) 24 (20)
Urogenital System 21 (29) 7 (15) 28 (23)
  Breast Pain 4 (6) 3 (6) 7 (6)
  Dysmenorrhea 10 (14) 3 (6) 13 (11)
  Metrorrhagia 10 (14) 3 (6) 13 (11)
a) Combined results for 0.625 mg and 2 x 0.625 mg Cenestin Tablets

In a second 12-week clinical trial that included 52 women treated with 0.45 mg Cenestin and 51 women treated with placebo, adverse reactions that occurred at a rate of >5 percent are summarized in Table 2.

Table 2: Number (%) of Patients with a ≥ 5 Percent Occurrence Rate by Body System and Treatment Group

Body System and Term Cenestin
0.45 mg
Placebo
Any Adverse Reaction (%) 40 (75.5%) 39 (76.5%)
Body As A Whole 20 (37.7%) 24 (47.1%)
Asthenia 6 (11.3%) 7 (13.7%)
Headache 6 (11.3%) 8 (15.7%)
Infection 1 (1.9%) 6 (11.8%)
Pain 6 (11.3%) 1 (2.0%)
Pain abdominal 5 (9.4%) 3 (5.9%)
Cardiovascular 5 (9.4%) 10 (19.6%)
Palpitations 3 (5.7%) 3 (5.9%)
Vasodilations 2 (3.8%) 4 (7.8%)
Digestive 8 (15.1%) 7 (13.7%)
Metabolic and Nutritional 5 (9.4%) 3 (5.9%)
Weight increase 3 (5.7%) 2 (3.9%)
Musculoskeletal 5 (9.4%) 6 (11.8%)
Arthralgia 5 (9.4%) 5 (9.8%)
Myalgia 2 (3.8%) 6 (11.8%)
Neurological 15 (28.3%) 19 (37.3%)
Anxiety 3 (5.7%) 1 (2.0%)
Insomnia 3 (5.7%) 5 (9.8%)
Nervousness 2 (3.8%) 7 (13.7%)
Paresthesia 4 (7.5%) 3 (5.9%)
Vertigo 3 (5.7%) 3 (5.9%)
Respiratory 10 (18.9%) 6 (11.8%)
Rhinitis 3 (5.7%) 2 (3.9%)
Urogenital 19 (35.8%) 7 (13.7%)
Endometrial thickening 10 (18.9%) 4 (7.8%)
Vaginitis 4 (7.5%) 1 (2.0%)
If a subject experiences the same event more than once, the first occurrence is tabulated.

In a 16-week clinical trial that included 36 women treated with 0.3 mg Cenestin and 34 women treated with placebo, adverse reactions that occurred at a rate of ≥5 percent are summarized in Table 3.

Table 3: Number (%) of Patients with Adverse Reactions with ≥ 5 Percent Occurrence Rate By Body System and Treatment Group

Body System and Term Cenestin
0.30 mg
Placebo
Body as a Whole 22 (60) 13 (38)
Allergic Reaction 3 (8) 1 (3)
Flu Syndrome 3 (8) 1 (3)
Injury Accident 2 (5) 1 (3)
Back Pain 2 (5) 1 (3)
Cyst 2 (5) 0 (0)
Asthenia 3 (8) 2 (6)
Digestive 10 (27) 8 (24)
Nausea 4 (11) 2 (6)
Dyspepsia 2 (5) 1 (3)
Vomiting 3 (8) 0 (0)
Increased Appetite 2 (5) 0 (0)
Neurological 7 (19) 7 (21)
Dizziness 3 (8) 0 (0)
Urogenital 22 (60) 16 (47)
Leukorrhea 12 (32) 5 (15)
Vaginitis 9 (24) 5 (15)
Urinary Incontinence 3 (8) 1 (3)
Metrorrhagia 2 (5) 0 (0)
Urinary Frequency 2 (5) 0 (0)

Post Marketing Experience

The following adverse reactions have been identified during post-approval use of Cenestin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

What drugs interact with Cenestin (conjugated estrogens)?

  • No drug-drug interaction studies have been conducted with Cenestin.

Metabolic Interactions

Treatment & Diagnosis

Medications & Supplements

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Medically Reviewed on 1/7/2021
References
FDA Prescribing Information

Professional side effects and drug interactions sections courtesy of the U.S. Food and Drug Administration.